Prolonged maintenance of capsaicin-induced hyperalgesia by brief daily vibration stimuli.

Science.gov (United States)

Kim, Hee Kee; Schattschneider, Jörn; Lee, Inhyung; Chung, Kyungsoon; Baron, Ralf; Chung, Jin Mo

2007-05-01

This study tests the hypothesis that central sensitization initiated by nociceptive input can be maintained by repeated brief innocuous peripheral inputs. Capsaicin was injected intradermally into the hind paw of adult rats. Three different types of daily cutaneous mechanical stimulations (vibration, soft brush, or pressure) were applied to the capsaicin-injected paw for a period of 2 weeks. Daily stimulation consisted of a 10-s stimulation repeated every 30s for 30 min. Foot withdrawal thresholds to von Frey stimuli applied to the paw were measured once a day for 4 weeks. The capsaicin-only group (control rats without daily stimulation) showed hyperalgesia lasting for 3 days. In contrast, hyperalgesia persisted for 2 weeks in the group that received vibration stimulation. Neither the soft brush nor the pressure group showed a significant difference in mechanical threshold from the control group (capsaicin only). The vibration-induced prolonged hyperalgesia was significantly reduced by systemic injection of ifenprodil, an NMDA-receptor antagonist, but it was not influenced by either an AMPA-receptor blocker or a reactive oxygen species (ROS) scavenger. Furthermore, a dorsal column lesion did not interfere with the prolongation of hyperalgesia. Data suggest that vibration-induced prolongation of hyperalgesia is mediated by spinal NMDA-receptors, and a similar mechanism may underlie some forms of chronic pain with no obvious causes, such as complex regional pain syndrome type 1 (CRPS-1).

Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

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Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

2017-01-01

Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

Comparison of remifentanil and low-dose fentanyl for fast-track cardiac anesthesia

DEFF Research Database (Denmark)

Khanykin, Boris; Siddiqi, Rizwan; Jensen, Per F

2013-01-01

BACKGROUND: Different anesthetic techniques have been used for fast tracking in cardiac anesthesia. Remifentanil, with its unique pharmacokinetic profile, could be an ideal drug for fast tracking. Possible limitations of remifentanil are rapid onset of postoperative pain after discontinuation...... of the drug infusion, which may increase the risk of an ischemic event. We conducted this randomized study to compare the efficacy of remifentanil versus low doses of fentanyl in fast-track cardiac anesthesia. It has been hypothesized that remifentanil would provide a safe anesthesia with no impact...... anesthesia. The study was designed as a prospective randomized study. The primary outcomes were changes in the cardiac index and creatine kinase MB fraction (CKMB), extubation times, mobilization times, and lengths of stay in the intensive care unit (ICU) and the hospital. Frequency of myocardial infarction...

Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

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Alvarez, Pedro; Green, Paul G; Levine, Jon D

2018-06-01

Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

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Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

2016-09-01

There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

Chronic vitamin C administration induces thermal hyperalgesia in ...

African Journals Online (AJOL)

Against a backdrop of neurological effects, the effects of acute and chronic administration of vitamin C (600mg/kg) on pain processing were investigated in male rats. Chronic administration of vitamin C induced significant thermal hyperalgesia while acute administration had no effect. In addition, the intraperitoneal ...

Pharmacodynamics of remifentanil. Induced intracranial spike activity in mesial temporal lobe epilepsy

DEFF Research Database (Denmark)

Kjær, Troels Wesenberg; Hogenhaven, Hans; Lee, Andrea P

2017-01-01

that remifentanil potentiates spike activity is in agreement with previous findings from smaller studies. Furthermore, we were able to describe the pharmacodynamics of the remifentanil effect on spike activity. Peri-operative provocation with remifentanil may play a future role in guiding neurosurgical intervention...

Experimental occlusal interference induces long-term masticatory muscle hyperalgesia in rats.

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Cao, Ye; Xie, Qiu-Fei; Li, Kai; Light, Alan R; Fu, Kai-Yuan

2009-08-01

Temporomandibular joint or related masticatory muscle pain represents the most common chronic orofacial pain condition. Patients frequently report this kind of pain after dental alterations in occlusion. However, lack of understanding of the mechanisms of occlusion-related temporomandibular joint and muscle pain prevents treating this problem successfully. To explore the relationship between improper occlusion (occlusal interference) and masticatory muscle pain, we created an occlusal interference animal model by directly bonding a crown to a maxillary molar to raise the masticating surface of the tooth in rats. We raised the occlusal surface to three different heights (0.2, 0.4, and 0.6mm), and for one month we quantitatively measured mechanical nociceptive thresholds of the temporal and masseter muscles on both sides. Results showed a stimulus-response relationship between the height of occlusal interference and muscle hyperalgesia. Removal of the crown 6 days after occlusal interference showed that the removal at this time could not terminate the 1 month duration of mechanical hyperalgesia in the masticatory muscles. Lastly, we systemically administered NMDA antagonist MK801 (0.2, 0.1, and 0.05 mg/kg) to the treated rats and found that MK801 dose dependently attenuated the occlusal interference-induced hyperalgesia. These findings suggest that occlusal interference is directly related to masticatory muscle pain, and that central sensitization mechanisms are involved in the maintenance of the occlusal interference-induced mechanical hyperalgesia.

Comparison of clinical efficacy among remifentanil, nicardipine, and remifentanil plus nicardipine continuous infusion for hypotensive anesthesia during arthroscopic shoulder surgery.

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Kim, Joon Yub; Song, Seong Hun; Cho, Jae Ho; Cho, Hyung Rae

2017-01-01

Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility. The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil, nicardipine, and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery. For this study, we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and randomly allocated them into remifentanil (group R, n = 15), nicardipine (group N, n = 15), and remifentanil plus nicardipine (group RN, n = 15) groups. During the surgeries, these drugs were administered with continuous infusion. We analyzed the mean arterial pressure (MAP) and heart rate during surgery, stay time in the recovery room, visual analogue scale (VAS) scores, use of antiemetics in the recovery room, and postoperative blood urea nitrogen and creatinine changes. The VAS score in the recovery room was higher for group R (mean 5.6, SD 1.4) than for groups N (mean 3.9, SD 0.9) and RN (mean 4.0, SD 1.1; p = 0.000). There were no statistical differences regarding other clinical variables among the three groups (all p > 0.05) except for MAP at 120 min of surgery between groups N and RN (N: 84.67 (SD 10.7) mmHg, RN: 65.4 (SD 9.2) mmHg, p = 0.027). The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit.

Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes.

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Siamak Djafarzadeh

Full Text Available During sepsis, liver dysfunction is common, and failure of mitochondria to effectively couple oxygen consumption with energy production has been described. In addition to sepsis, pharmacological agents used to treat septic patients may contribute to mitochondrial dysfunction. This study addressed the hypothesis that remifentanil interacts with hepatic mitochondrial oxygen consumption. The human hepatoma cell line HepG2 and their isolated mitochondria were exposed to remifentanil, with or without further exposure to tumor necrosis factor-α (TNF-α. Mitochondrial oxygen consumption was measured by high-resolution respirometry, Caspase-3 protein levels by Western blotting, and cytokine levels by ELISA. Inhibitory κBα (IκBα phosphorylation, measurement of the cellular ATP content and mitochondrial membrane potential in intact cells were analysed using commercial ELISA kits. Maximal cellular respiration increased after one hour of incubation with remifentanil, and phosphorylation of IκBα occurred, denoting stimulation of nuclear factor κB (NF-κB. The effect on cellular respiration was not present at 2, 4, 8 or 16 hours of incubation. Remifentanil increased the isolated mitochondrial respiratory control ratio of complex-I-dependent respiration without interfering with maximal respiration. Preincubation with the opioid receptor antagonist naloxone prevented a remifentanil-induced increase in cellular respiration. Remifentanil at 10× higher concentrations than therapeutic reduced mitochondrial membrane potential and ATP content without uncoupling oxygen consumption and basal respiration levels. TNF-α exposure reduced respiration of complex-I, -II and -IV, an effect which was prevented by prior remifentanil incubation. Furthermore, prior remifentanil incubation prevented TNF-α-induced IL-6 release of HepG2 cells, and attenuated fragmentation of pro-caspase-3 into cleaved active caspase 3 (an early marker of apoptosis. Our data suggest that

Evaluation of antivenoms in the neutralization of hyperalgesia and edema induced by Bothrops jararaca and Bothrops asper snake venoms

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Picolo G.

2002-01-01

Full Text Available Neutralization of hyperalgesia induced by Bothrops jararaca and B. asper venoms was studied in rats using bothropic antivenom produced at Instituto Butantan (AVIB, 1 ml neutralizes 5 mg B. jararaca venom and polyvalent antivenom produced at Instituto Clodomiro Picado (AVCP, 1 ml neutralizes 2.5 mg B. aspar venom. The intraplantar injection of B. jararaca and B. asper venoms caused hyperalgesia, which peaked 1 and 2 h after injection, respectively. Both venoms also induced edema with a similar time course. When neutralization assays involving the independent injection of venom and antivenom were performed, the hyperalgesia induced by B. jararaca venom was neutralized only when bothropic antivenom was administered iv 15 min before venom injection, whereas edema was neutralized when antivenom was injected 15 min or immediately before venom injection. On the other hand, polyvalent antivenom did not interfere with hyperalgesia or edema induced by B. asper venom, even when administered prior to envenomation. The lack of neutralization of hyperalgesia and edema induced by B. asper venom is not attributable to the absence of neutralizing antibodies in the antivenom, since neutralization was achieved in assays involving preincubation of venom and antivenom. Cross-neutralization of AVCP or AVIB against B. jararaca and B. asper venoms, respectively, was also evaluated. Only bothropic antivenom partially neutralized hyperalgesia induced by B. asper venom in preincubation experiments. The present data suggest that hyperalgesia and edema induced by Bothrops venoms are poorly neutralized by commercial antivenoms even when antibodies are administered immediately after envenomation.

Peripheral lidocaine, but not ketamine inhibit capsaicin-induced hyperalgesia in humans

DEFF Research Database (Denmark)

Gottrup, Hanne; Bach, Flemming Winther; Arendt-Nielsen, Lars

2000-01-01

We examined the effect of the subcutaneous infiltration of ketamine, lidocaine and saline before injury on capsaicin-induced pain and hyperalgesia. Twelve healthy volunteers participated in two separate, randomized, double-blind, placebo-controlled crossover experiments. In experiment 1, 100...... micrograms capsaicin was injected intradermally in one volar forearm 10 min after the skin had been pretreated with lidocaine 20.0 mg in 2.0 ml or 0.9% saline 2.0 ml at the capsaicin injection site. In experiment 2, a similar capsaicin test was given 10 min after the skin had been pretreated with ketamine 5...... and brush stimuli, and areas of brush-evoked and punctate-evoked hyperalgesia. Lidocaine reduced all measures compared with placebo (P ketamine failed to change any measures. Pain scores and areas of hyperalgesia were not affected when the contralateral site was infiltrated with ketamine...

Safety of remifentanil in transsphenoidal surgery: A single-center analysis of 540 patients.

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Cote, David J; Burke, William T; Castlen, Joseph P; King, Chih H; Zaidi, Hasan A; Smith, Timothy R; Laws, Edward R; Aglio, Linda S

2017-04-01

Although some studies have examined the efficacy and safety of remifentanil in patients undergoing neurosurgical procedures, none has examined its safety in transsphenoidal operations specifically. In this study, all transsphenoidal operations performed by a single author from 2008 to 2015 were retrospectively reviewed to evaluate the safety of remifentanil in a consecutive series of patients. During the study period, 540 transsphenoidal operations were identified. Of these, 443 (82.0%) patients received remifentanil intra-operatively; 97 (18.0%) did not. The two groups were well-matched with regard to demographic categories, comorbidities, and pre-operative medications (p>0.05), except pre-operative tobacco use (p=0.021). Patients were also well-matched with regard to radiographic features and surgical techniques. Patients who received remifentanil were more likely to harbor a macroadenoma (78.1% vs. 67.0%, p=0.025), and had slightly longer anesthesia time on average (269.2minvs. 239.4min, p=0.024). All pathologic diagnoses were well-matched between the two groups, except that patients receiving remifentanil were more likely to harbor a non-functioning adenoma (46.5% vs. 26.8%, ptranssphenoidal surgery, remifentanil was found to be a safe anesthetic adjunct. There were no significant differences in post-operative hospital course or complications in patients who did and did not receive intra-operative remifentanil. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression

Science.gov (United States)

Song, Zhi-Jing; Miao, Shuai; Zhao, Ye; Wang, Xiu-Li; Liu, Yue-Peng

2018-01-01

Purpose Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance. Methods Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine. To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH) and tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA (siRNA) were used. To explore the mechanisms of Shh signaling in MIH and tolerance, brain-derived neurotrophic factor (BDNF) inhibitor K252 and anti-BDNF antibody were used. Results Repeated administration of morphine produced obvious hyperalgesia and tolerance. The behavioral changes were correlated with the upregulation and activation of morphine treatment-induced Shh signaling. Pharmacologic and genetic inhibition of Shh signaling significantly delayed the generation of MIH and tolerance and associated neurochemical changes. Chronic morphine administration also induced upregulation of BDNF. Inhibiting BDNF effectively delayed the generation of MIH and tolerance. The upregulation of BDNF induced by morphine was significantly suppressed by inhibiting Shh signaling. In naïve mice, exogenous activation of Shh signaling caused a rapid increase of BDNF expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly suppressed smoothened agonist-induced hyperalgesia. Conclusion These findings suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating BDNF expression. Inhibiting Shh signaling, especially during the early phase, may effectively delay or suppress MIH and tolerance. PMID:29662325

Remifentanil in combination with ketamine versus remifentanil in spinal fusion surgery--a double blind study.

Science.gov (United States)

Hadi, B A; Al Ramadani, R; Daas, R; Naylor, I; Zelkó, R

2010-08-01

This study is aimed at conducting a program for two different anesthetic methods used during a spinal fusion surgery to ensure better intra-operative hemodynamic stability and post-operative pain control. A prospective, randomized, double blind study in patients scheduled for spinal fusion surgery, who were randomly allocated to two groups, G1 and G2, (n = 15 per group), class I-II ASA, was carried out. Both groups received pre-operatively midazolam, followed intra-operatively by propofol, sevoflurane, atracurium, and either remifentanil infusion 0.2 microg/kg/min (G1), or the same dose of remifentanil infusion and low doses of ketamine infusion 1 microg/kg/min (G2) anesthetics, antidote medication and post-operative morphine doses. HR, MAP, vital signs, surgical bleeding, urine output, duration of surgery and duration of anesthesia were recorded. In a 24-h recovery period in a post-anesthesia care unit (PACU) the recovery time, the first pain score and analgesic requirements were measured. Intra-operative HR and arterial BP were significantly less (p < 0.05) in G1 as compared to G2. In the PACU the first pain scores were significantly less (p < 0.05) in G2 than in G1. The time for the first patient analgesia demand dose was greater in G2, as also morphine consumption which was greater in G1 than G2 (p < 0.05). Other results were the same. None of the patients had any adverse drug reaction. Adding low doses of ketamine hydrochloride could be a routine therapy to improve the hemodynamic stability and reduce the post-operative morphine consumption during spinal fusion surgery.

PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα

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Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

2016-01-01

Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

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Xiaoyu Hu

Full Text Available Opioid-induced hyperalgesia (OIH is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

Remifentanil-induced spike activity as a diagnostic tool in epilepsy surgery

DEFF Research Database (Denmark)

Grønlykke, L; Knudsen, M L; Høgenhaven, H

2008-01-01

To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE).......To assess the value of remifentanil in intraoperative evaluation of spike activity in patients undergoing surgery for mesial temporal lobe epilepsy (MTLE)....

Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

Science.gov (United States)

Choi, Byung In; Choi, Seung Ho; Shin, Yang-Sik; Lee, Sung Jin; Yoon, Kyung Bong; Shin, Seo Kyung

2008-01-01

Purpose The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. Materials and Methods Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n = 30), 0.5 µg/kg remifentanil (Group II, n = 30) or 1 µg/kg remifentanil (Group III, n = 30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. Results The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. Conclusion The pretreatment with 0.5 and 1.0 µg/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation. PMID:18452256

Role of TRPV1 and ASIC3 channels in experimental occlusal interference-induced hyperalgesia in rat masseter muscle.

Science.gov (United States)

Xu, X X; Cao, Y; Ding, T T; Fu, K Y; Li, Y; Xie, Q F

2016-04-01

Masticatory muscle pain may occur following immediate occlusal alteration by dental treatment. The underlying mechanisms are poorly understood. Transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channel-3 (ASIC3) mediate muscle hyperalgesia under various pathologic conditions. We have developed a rat model of experimental occlusal interference (EOI) that consistently induces mechanical hyperalgesia in jaw muscles. Whether TRPV1 and ASIC3 mediate this EOI-induced hyperalgesia is unknown. Rat model of EOI-induced masseter hyperalgesia was established. Real-time polymerase chain reaction, Western blot and retrograde labelling combined with immunofluorescence were performed to evaluate the modulation of TRPV1 and ASIC3 expression in trigeminal ganglia (TGs) and masseter afferents of rats after EOI. The effects of intramuscular administration of TRPV1 and ASIC3 antagonists on the EOI-induced hyperalgesia in masseter muscle were examined. After EOI, gene expressions and protein levels of TRPV1 and ASIC3 in bilateral TGs were up-regulated. The percentage of ASIC3- (but not TRPV1-) positive neurons in masseter afferents increased after EOI. More small-sized and small to medium-sized masseter afferents expressed TRPV1 and ASIC3 separately following EOI. These changes peaked at day 7 and then returned to original status within 10 days after EOI. Intramuscular administration of the TRPV1 antagonist AMG-9810 partially reversed this mechanical hyperalgesia in masseter muscle. No improvement was exhibited after administration of the ASIC3 antagonist APETx2. Co-injection of AMG-9810 and APETx2 enhanced the effect of AMG-9810 administration alone. Peripheral TRPV1 and ASIC3 contribute to the development of the EOI-induced mechanical hyperalgesia in masseter muscle. © 2015 European Pain Federation - EFIC®

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

DEFF Research Database (Denmark)

Larsen, Malte Selch; Keizer, Ron; Munro, Gordon

2016-01-01

PURPOSE: Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA......-induced inflammatory hyperalgesia. METHODS: A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration...

Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

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Theresa Alexandra Mattioli

Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

Ranolazine attenuation of CFA-induced mechanical hyperalgesia.

Science.gov (United States)

Casey, Gregory P; Roberts, Jomar S; Paul, Dennis; Diamond, Ivan; Gould, Harry J

2010-01-01

To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain. Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration. Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia. Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.

Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression

Directory of Open Access Journals (Sweden)

Liu S

2018-04-01

Full Text Available Su Liu,1,2,* Jun-Li Yao,1,3,* Xin-Xin Wan,1,* Zhi-Jing Song,1 Shuai Miao,1,2 Ye Zhao,1,2 Xiu-Li Wang,1,2 Yue-Peng Liu4 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China; 2Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; 3Department of Anesthesiology, Xuzhou Children’s Hospital, Xuzhou, Jiangsu, China; 4Center of Clinical Research and Translational Medicine, Lianyungang Oriental Hospital, Lianyungang, Jiangsu, China *These authors contributed equally to this work Purpose: Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh signaling in opioid-induced hyperalgesia and tolerance. Methods: Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine. To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH and tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA (siRNA were used. To explore the mechanisms of Shh signaling in MIH and tolerance, brain-derived neurotrophic factor (BDNF inhibitor K252 and anti-BDNF antibody were used. Results: Repeated administration of morphine produced obvious hyperalgesia and tolerance. The behavioral changes were correlated with the upregulation and activation of morphine treatment-induced Shh signaling. Pharmacologic and genetic inhibition of Shh signaling significantly delayed the generation of MIH and tolerance and associated neurochemical changes. Chronic morphine administration also induced upregulation of BDNF. Inhibiting BDNF effectively delayed the generation of MIH and tolerance. The upregulation of BDNF induced by morphine was significantly suppressed by inhibiting Shh

Relation cellular- molecular between serum IL10 levels and hyperalgesia variation in adjuvant- induced arthritis

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Zenab Akhtari

2015-01-01

Full Text Available Background: Regarding to the important anti-inflammatory role of IL10 during inflammation process and hyperalgesia and edema variation during CFA-induced arthritis and also the increase of Spinal mu opioid receptor (mOR expression, in this study researchers investigate the role of serum IL10 level on mOR expression and edema and hyperalgesia variation during different stages of Complete Freund`s Adjuvant (CFA - induced arthritis in male Wistar rats. Materials and Methods: Mono-arthritis was induced by CFA and inflammatory symptoms (hyperalgesia and edema were assessed on 0, 3, 7, 14th and 21st days of study. Anti-IL10 was administered during the 21 days of study in different experimental groups. mOR expression were detected by western blotting on 0, 3,7, 14th and 21st days of study. Data was analyzed by SPSS statistical software version 19 with using one way ANOVA (post hoc Tokey's. Results: Our results showed that anti-IL10 administration in AA group (Adjuvant Arthritis caused an increase in the paw volume and hyperalgesia until 21st of study. Our study stated that there were no significant differences in spinal mOR expression between AA and AA+anti-IL10rats. Conclusion: Our study confirmed that anti-IL10administration caused to hyperalgesia and edema during AA inflammation. Also these findings suggested that mOR expression increased in chronic phase of AA inflammation, however an increase in the level of spinal mu opioid receptor (mOR expression during AA inflammation is not mediated directly via the effect of serum IL-10.

Acute restraint stress induces hyperalgesia via non-adrenergic ...

African Journals Online (AJOL)

Analgesia or hyperalgesia has been reported to occur in animals under different stress conditions. This study examined the effect of acute restraint stress on nociception in rats. Acute restraint stress produced a time-dependant decrease in pain threshold; this hyperalgesia was not affected by prior administration of ...

The influence of propofol, remifentanil and lidocaine on the tone of human bronchial smooth muscle.

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Rogliani, Paola; Calzetta, Luigino; Rendina, Erino A; Massullo, Domenico; Dauri, Mario; Rinaldi, Barbara; Capuano, Annalisa; Matera, Maria Gabriella

2013-06-01

Bronchoscopy is generally a safe procedure, but the induction of anaesthesia can induce bronchospasm. Consequently we investigated the influence of propofol, remifentanil and lidocaine on the tone of the human bronchial smooth muscle. The influence of propofol, remifentanil and lidocaine on the contractile response of human bronchial smooth muscle to electrical field stimulation (EFS) has been evaluated. The role of capsaicin-sensitive sensory nerves and of inducible nitric oxide synthase has also been assessed. Furthermore, the interaction between these three dugs has been measured by Bliss Independence (BI) theory. Statistical significance (P < 0.05) was assessed by Student's t test or ANOVA. Propofol (1.3 μg ml(-1)) and lidocaine (1 mg ml(-1)) reduced the baseline tone of bronchial rings (-14.45 ± 4.53% and -33.40 ± 1.07%, respectively, P < 0.05), whereas remifentanil had not such effect. Aminoguanidine prevented the relaxant effect of propofol. Propofol did not alter the bronchial contractile response to EFS following 30 min of treatment, whereas remifentanil enhanced the bronchial tension (133.83 ± 9.38%, control 101.93 ± 6.82%, P < 0.05 P < 0.05) and lidocaine completely abolished the contractility at 1 mg ml(-1) (P < 0.05). The desensitization of capsaicin-sensitive sensory nerves normalized the hyperresponsiveness induced by remifentanil (-26.77 ± 1.68%, P < 0.05). Significant BI antagonism (P < 0.001) was detected for propofol and lidocaine on the bronchial hyperresponsiveness induced by remifentanil. Propofol and remifentanil may be used safely for bronchoscopy, although remifentanil should be associated with propofol or lidocaine to prevent the potential opioid-mediated bronchospasm. Copyright © 2013 Elsevier Ltd. All rights reserved.

PCA-derived factors that may be predictive of postoperative pain in pediatric patients: a possible role for the PCA ratio.

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McDonnell, Conor; Pehora, Carolyne; Crawford, Mark W

2012-01-01

No method exists to reliably predict which patients will develop severe postoperative pain. The authors hypothesized that data derived from patient-controlled analgesia (PCA) pumps (specifically the ratio of patient demands to pump deliveries) may predict which patients would develop severe pain after scoliosis repair. Quaternary, university-affiliated, pediatric hospital. Forty American Society of Anesthesiologists I-Il pediatric patients who had undergone elective scoliosis repair and had consented to recruitment to a randomized clinical trial investigating the effects of early morphine administration on remifentanil-induced hyperalgesia. To test the hypothesis of the current study, the authors calculated the PCA ratio of demand to delivery at every 4 hours throughout the first 24 hours after surgery for all the patients recruited to the original study. The authors compared calculated PCA ratios, numeric rating scale pain scores, and cumulative morphine consumption for those patients who developed severe postoperative pain and met the criteria for opioid rotation versus those patients who did not. Seven patients required opioid rotation from PCA morphine to PCA hydromorphone. Eight hours after surgery, the median PCA ratio for those seven patients (2.5[range, 1.8-4.3]) was significantly greater than that for all other recruited patients (1.3 [range, 0-2.7]; p PCA ratios of demand to delivery as early as 8 hours after surgery.

Activation of ERK signalling by Src family kinases (SFKs) in DRG neurons contributes to hydrogen peroxide (H2O2)-induced thermal hyperalgesia.

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Singh, Ajeet Kumar; Vinayak, Manjula

2017-10-01

Concomitant generation of reactive oxygen species during tissue inflammation has been recognised as a major factor for the development and the maintenance of hyperalgesia, out of which H 2 O 2 is the major player. However, molecular mechanism of H 2 O 2 induced hyperalgesia is still obscure. The aim of present study is to analyse the mechanism of H 2 O 2 -induced hyperalgesia in rats. Intraplantar injection of H 2 O 2 (5, 10 and 20 µmoles/paw) induced a significant thermal hyperalgesia in the hind paw, confirmed by increased c-Fos activity in dorsal horn of spinal cord. Onset of hyperalgesia was prior to development of oxidative stress and inflammation. Rapid increase in phosphorylation of extracellular signal regulated kinase (ERK) was observed in neurons of dorsal root ganglia after 20 min of H 2 O 2 (10 µmoles/paw) administration, which gradually returned towards normal level within 24 h, following the pattern of thermal hyperalgesia. The expression of TNFR1 followed the same pattern and colocalised with pERK. ERK phosphorylation was observed in NF-200-positive and -negative neurons, indicating the involvement of ERK in C-fibres as well as in A-fibres. Intrathecal preadministration of Src family kinases (SFKs) inhibitor (PP1) and MEK inhibitor (PD98059) prevented H 2 O 2 induced augmentation of ERK phosphorylation and thermal hyperalgesia. Pretreatment of protein tyrosine phosphatases (PTPs) inhibitor (sodium orthovanadate) also diminished hyperalgesia, although it further increased ERK phosphorylation. Combination of orthovanadate with PP1 or PD98059 did not exhibit synergistic antihyperalgesic effect. The results demonstrate SFKs-mediated ERK activation and increased TNFR1 expression in nociceptive neurons during H 2 O 2 induced hyperalgesia. However, the role of PTPs in hyperalgesic behaviour needs further molecular analysis.

Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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Chai Bryan

2012-10-01

Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

Melatonin Alters the Mechanical and Thermal Hyperalgesia Induced by Orofacial Pain Model in Rats.

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Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Adachi, Lauren Naomi Spezia; de Macedo, Isabel Cristina; Cioato, Stefania Giotti; de Freitas, Joice S; de Souza, Andressa; Quevedo, Alexandre; Caumo, Wolnei; Torres, Iraci Lucena da Silva

2016-10-01

Melatonin is a neuroendocrine hormone that presents a wide range of physiological functions including regulating circadian rhythms and sleep, enhancing immune function, sleep improvement, and antioxidant effects. In addition, melatonin has received special attention in pain treatment since it is effective and presents few adverse effects. In this study, we evaluated the effect of acute dose of melatonin upon hyperalgesia induced by complete Freund's adjuvant in a chronic orofacial pain model in Sprague-Dawley rats. Nociceptive behavior was assessed by facial Von Frey and the hot plate tests at baseline and thereafter 30, 60, and 120 min, 24 h, and 7 days after melatonin treatment. We demonstrated that acute melatonin administration alters mechanical and thermal hyperalgesia induced by an orofacial pain model (TMD), highlighting that the melatonin effect upon mechanical hyperalgesia remained until 7 days after its administration. Besides, we observed specific tissue profiles of neuroimmunomodulators linked to pain conditions and/or melatonin effect (brain-derived neurotrophic factor, nerve growth factor, and interleukins 6 and 10) in the brainstem levels, and its effects were state-dependent of the baseline of these animals.

Local and Widespread Hyperalgesia After Isolated Tibial Shaft Fractures Treated with Intramedullary Nailing

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Larsen, Peter; Elsøe, Rasmus; Graven-Nielsen, Thomas

2016-01-01

OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months postopera...... fracture treated with intramedullary nailing, although no widespread (extrasegmental) hyperalgesia was detected. Such observations may be important for developing the most adequate rehabilitation procedure following a tibial fracture.......OBJECTIVES: Knee pain is accepted as a common complication to intramedullary nailing of tibial fractures. However, no studies have systematically studied the pain sequel following tibial fractures. The objective of this study was to assess pain and hyperalgesia from 6 weeks to 12 months...... postoperatively after intramedullary nailing of tibial shaft fracture. METHODS: A total of 39 patients were included in this 12-month follow-up study. After 6 weeks, 3, 6, and 12 months postoperatively the pain intensity was measured on a visual analog scale (VAS) and the pressure pain sensitivity was assessed...

Increased synaptophysin is involved in inflammation-induced heat hyperalgesia mediated by cyclin-dependent kinase 5 in rats.

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Hong-Hai Zhang

Full Text Available Mechanisms associated with cyclin-dependent kinase 5 (Cdk5-mediated heat hyperalgesia induced by inflammation remain undefined. This study was designed to examine whether Cdk5 mediates heat hyperalgesia resulting from peripheral injection of complete Freund's adjuvant (CFA in the spinal dorsal horns of rats by interacting with synaptophysin, a well known membrane protein mediating the endocytosis-exocytosis cycle of synaptic vesicles as a molecular marker associated with presynaptic vesicle membranes. The role of Cdk5 in mediating synaptophysin was examined through the combined use of behavioral approaches, imaging studies, and immunoprecipitation following CFA-induced inflammatory pain. Results showed that Cdk5 colocalized with both synaptophysin and soluble N-ethylmaleimide-sensitive factor (NSF attachment protein receptors (SNAREs consisting of VAMP-2, SNAP-25, and syntaxin 1A in spinal dorsal horn of rats. Increased synaptophysin expression of spinal cord horn neurons post intraplantar injection of CFA coincided with increased duration of heat hyperalgesia lasting from 6 h to 3 d. Intrathecal administration of roscovitine, a Cdk5 specific inhibitor, significantly depressed synaptophysin expression during peak heat hyperalgesia and heat hyperalgesia induced by peripheral injection of CFA. Data presented in this report indicated that calpain activity was transiently upregulated 6 h post CFA-treatment despite previous reports suggesting that calpain was capable of cleaving p35 into p25. Results from previous studies obtained by other laboratories demonstrated that significant changes in p35 expression levels within spinal cord horn neurons were not observed in the CFA-treated inflammatory pain model although significant upregulation of Cdk5 kinase was observed between 2 h to 7 d. Therefore, generation of p25 occurred in a calpain-independent fashion in a CFA-treated inflammatory pain model. Our results demonstrated that increased synaptophysin

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition, Cytokines and Kinin Receptors Modulation.

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Nikele Nadur-Andrade

2016-10-01

Full Text Available Envenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv, as well as the mechanisms involved was investigated.Bmv (1 μg was injected through the intraplantar route in the right hind paw of mice. Mechanical hyperalgesia and allodynia were evaluated by von Frey filaments at different time points after venom injection. Low level laser therapy (LLLT was applied at the site of Bmv injection at wavelength of red 685 nm with energy density of 2.2 J/cm2 at 30 min and 3 h after venom inoculation. Neuronal activation in the dorsal horn spinal cord was determined by immunohistochemistry of Fos protein and the mRNA expression of IL-6, TNF-α, IL-10, B1 and B2 kinin receptors were evaluated by Real time-PCR 6 h after venom injection. Photobiomodulation reversed Bmv-induced mechanical hyperalgesia and allodynia and decreased Fos expression, induced by Bmv as well as the mRNA levels of IL-6, TNF-α and B1 and B2 kinin receptors. Finally, an increase on IL-10, was observed following LLLT.These data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.

Continous Infusion of Remifentanil Plus Ketamine Compared with Continous Remifentanil for Pain Relief in Labour

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Anooshe Khajehdehi

2011-12-01

Full Text Available Abstract Background and objective: Pain relief during labour is an important determinant of a women’s birth experience. There are numerous pain relief techniques which can be used either with or without pain medication. The aim of our study was to compare the effect of remifentanil alone and its effect in pain relief while using with ketamine during labour. Methods: After obtaining informed consent and approval of hospital ethics committee, 40 women with gestational age between 38 and 42 weeks gestation in early labour were recruited for this study. They were randomly allocated into two groups: group RK (20 cases received 25 μg remifentanil as a starting dose and continuous infusion of 0.06 μg/kg/min remifentanil plus 0.5 mg/kg/h ketamine for 4 hours via pump and group R (20 cases received 25 μg remifentanil as a starting dose and continous infusion of 0.06 μg/kg/min remifentanil. Results: The baseline of pain scores were similar in both groups (5.75 ± 2.51 vs 7 ± 2.45, p= 0.12 but after 30 minutes to 120 minutes the VAS scores were significantly higher in R group (p< 0.001. The rate of patients who were satisfied (excellent and very good in RK was 80% but in R group was 45% (p = 0.03. Nausea and vomiting were significantly higher in R group (p<0.05. Conclusion: The remifentanil plus ketamine produced better pain relief during labour with continous monitoring than continous remifentanil with no adverse effects for mothers and infants.

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

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Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Traumatic osteoarthritis-induced persistent mechanical hyperalgesia in a rat model of anterior cruciate ligament transection plus a medial meniscectomy

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Tsai HC

2017-12-01

after 5 weeks but persisted. There were no differences in thermal hyperalgesia or motor coordination. Conclusion: Traumatic OA induced mechanical hyperalgesia but did not cause thermal hyperalgesia or influence motor coordination. Furthermore, to investigate chronic pain induced by OA, the observational period should be at least 5 weeks after the intervention. These findings may help in further research and improve our understanding of traumatic OA-induced pain mechanisms. Keywords: traumatic osteoarthritis, acute and chronic pain, mechanical hyperalgesia, thermal hyperalgesia, motor coordination

The Effect of EMLA Cream on Patient-Controlled Analgesia with Remifentanil in ESWL Procedure: A Placebo-Controlled Randomized Study.

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Acar, Arzu; Erhan, Elvan; Nuri Deniz, M; Ugur, Gulden

2013-01-01

To alleviate stinging pain in the skin entry area and visceral discomfort in patients who are undergoing ESWL. This study was designed to investigate the effectiveness of the EMLA cream in combination with remifentanil patient-controlled analgesia (PCA) in patients undergoing ESWL treatment. Sixty patients were divided into two double-blind randomized groups. Those in the first group were administered 3-5mm of EMLA 5% cream on a marked area; the second group received, as a placebo, a cream with no analgesic effect in the same amount. All patients were administered a remifentanil bolus with a PCA device. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; postoperative side effects, agitation, and respiratory depression were measured after. Visual Analogue Scale (VAS) scores were taken preoperatively, perioperatively, directly postoperatively, and 60 minutes subsequent to finishing the procedure. There were no statistically significant differences in the frequency of PCA demands and delivered boluses or among perioperative VAS. No significant side effects were noted. Patient satisfaction was recorded high in both groups. EMLA cream offered no advantage over the placebo cream in patients undergoing ESWL with remifentanil PCA.

The Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia.

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Ackerman, A Lenore; Jellison, Forrest C; Lee, Una J; Bradesi, Sylvie; Rodríguez, Larissa V

2016-04-01

Psychological stress exacerbates interstitial cystitis/bladder pain syndrome (IC/BPS), a lower urinary tract pain disorder characterized by increased urinary frequency and bladder pain. Glutamate (Glu) is the primary excitatory neurotransmitter modulating nociceptive networks. Glt1, an astrocytic transporter responsible for Glu clearance, is critical in pain signaling termination. We sought to examine the role of Glt1 in stress-induced bladder hyperalgesia and urinary frequency. In a model of stress-induced bladder hyperalgesia with high construct validity to human IC/BPS, female Wistar-Kyoto (WKY) rats were subjected to 10-day water avoidance stress (WAS). Referred hyperalgesia and tactile allodynia were assessed after WAS with von Frey filaments. After behavioral testing, we assessed Glt1 expression in the spinal cord by immunoblotting. We also examined the influence of dihydrokainate (DHK) and ceftriaxone (CTX), which downregulate and upregulate Glt1, respectively, on pain development. Rats exposed to WAS demonstrated increased voiding frequency, increased colonic motility, anxiety-like behaviors, and enhanced visceral hyperalgesia and tactile allodynia. This behavioral phenotype correlated with decreases in spinal Glt1 expression. Exogenous Glt1 downregulation by DHK resulted in hyperalgesia similar to that following WAS. Exogenous Glt1 upregulation via intraperitoneal CTX injection inhibited the development of and reversed preexisting pain and voiding dysfunction induced by WAS. Repeated psychological stress results in voiding dysfunction and hyperalgesia that correlate with altered central nervous system glutamate processing. Manipulation of Glu handling altered the allodynia developing after psychological stress, implicating Glu neurotransmission in the pathophysiology of bladder hyperalgesia in the WAS model of IC/BPS. Copyright © 2016 the American Physiological Society.

A Rat Model of Full Thickness Thermal Injury Characterized by Thermal Hyperalgesia, Mechanical Allodynia, Pronociceptive Peptide Release and Tramadol Analgesia

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2014-01-01

tramadol reduces acute, postoperative, neuropathic and cancer pain [9,10,12 14] and may have a lower propensity to induce addiction [15] with little to...opioid systems simultaneously, we next examined whether tramadol could attenuate burn evoked pain behaviors in our rat model of full thickness thermal...injury. Tramadol attenuated thermal hyperalgesia when administered one week following thermal injury, a time point when pain behaviors peak in this

Intraoperative esmolol infusion reduces postoperative analgesic consumption and anaesthetic use during septorhinoplasty: a randomized trial

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Nalan Celebi

2014-09-01

Full Text Available Background and objectives: Esmolol is known to have no analgesic activity and no anaesthetic properties; however, it could potentiate the reduction in anaesthetic requirements and reduce postoperative analgesic use. The objective of this study is to evaluate the effect of intravenous esmolol infusion on intraoperative and postoperative analgesic consumptions as well as its effect on depth of anaesthesia. Methods: This randomized-controlled double blind study was conducted in a tertiary care hospital between March and June 2010. Sixty patients undergoing septorhinoplasty were randomized into two groups. History of allergy to drugs used in the study, ischaemic heart disease, heart block, bronchial asthma, hepatic or renal dysfunction, obesity and a history of chronic use of analgesic or β-blockers were considered cause for exclusion from the study. Thirty patients received esmolol and remifentanil (esmolol group and 30 patients received normal saline and remifentanil (control group as an intravenous infusion during the procedure. Mean arterial pressure, heart rate, and bispectral index values were recorded every 10min. Total remifentanil consumption, visual analogue scale scores, time to first analgesia and total postoperative morphine consumption were recorded. Results: The total remifentanil consumption, visual analogue scale scores at 0, 20 and 60 min, total morphine consumption, time to first analgesia and the number of patients who needed an intravenous morphine were lower in the esmolol group. Conclusions: Intravenous infusion of esmolol reduced the intraoperative and postoperative analgesic consumption, reduced visual analogue scale scores in the early postoperative period and prolonged the time to first analgesia; however it did not influence the depth of anaesthesia.

Pretreatment with remifentanil protects against the reduced-intestinal contractility related to the ischemia and reperfusion injury in rat

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Hale Sayan-Ozacmak

2015-12-01

Full Text Available BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min followed by reperfusion (3 h. Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1 for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.

TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.

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Honda, Kuniya; Shinoda, Masamichi; Furukawa, Akihiko; Kita, Kozue; Noma, Noboru; Iwata, Koichi

2014-12-01

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection. © 2014 Eur J Oral Sci.

Topical thermal therapy with hot packs suppresses physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF.

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Nakagawa, Tatsuki; Hiraga, Shin-Ichiro; Mizumura, Kazue; Hori, Kiyomi; Ozaki, Noriyuki; Koeda, Tomoko

2017-10-12

We focused on the analgesic effect of hot packs for mechanical hyperalgesia in physically inactive rats. Male Wistar rats were randomly divided into four groups: control, physical inactivity (PI), PI + sham treatment (PI + sham), and PI + hot pack treatment (PI + hot pack) groups. Physical inactivity rats wore casts on both hind limbs in full plantar flexed position for 4 weeks. Hot pack treatment was performed for 20 min a day, 5 days a week. Although mechanical hyperalgesia and the up-regulation of NGF in the plantar skin and gastrocnemius muscle were observed in the PI and the PI + sham groups, these changes were significantly suppressed in the PI + hot pack group. The present results clearly demonstrated that hot pack treatment was effective in reducing physical inactivity-induced mechanical hyperalgesia and up-regulation of NGF in plantar skin and gastrocnemius muscle.

Facial hyperalgesia due to direct action of endothelin-1 in the trigeminal ganglion of mice.

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Gomes, Lenyta Oliveira; Chichorro, Juliana Geremias; Araya, Erika Ivanna; de Oliveira, Jade; Rae, Giles Alexander

2018-03-23

This study assessed the ability of endothelin-1 (ET-1) to evoke heat hyperalgesia when injected directly into the trigeminal ganglia (TG) of mice and determined the receptors implicated in this effect. The effects of TG ET A and ET B receptor blockade on alleviation of heat hyperalgesia in a model of trigeminal neuropathic pain induced by infraorbital nerve constriction (CION) were also examined. Naive mice received an intraganglionar (i.g.) injection of ET-1 (0.3-3 pmol) or the selective ET B R agonist sarafotoxin S6c (3-30 pmol), and response latencies to ipsilateral heat stimulation were assessed before the treatment and at 1-h intervals up to 5 h after the treatment. Heat hyperalgesia induced by i.g. ET-1 or CION was assessed after i.g. injections of ET A R and ET B R antagonists (BQ-123 and BQ-788, respectively, each at 0.5 nmol). Intraganglionar ET-1 or sarafotoxin S6c injection induced heat hyperalgesia lasting 4 and 2 h, respectively. Heat hyperalgesia induced by ET-1 was attenuated by i.g. BQ-123 or BQ-788. On day 5 after CION, i.g. BQ-788 injection produced a more robust antihyperalgesic effect compared with BQ-123. ET-1 injection into the TG promotes ET A R/ET B R-mediated facial heat hyperalgesia, and both receptors are clearly implicated in CION-induced hyperalgesia in the murine TG system. © 2018 Royal Pharmaceutical Society.

Altered cortical causality after remifentanil administration in healthy volunteers

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Khodayari-Rostamabad, Ahmad; Graversen, Carina; Olesen, Soren S

2014-01-01

and after infusion of remifentanil and placebo. Additionally, to assess cognitive function and analgesic effect, continuous reaction time (CRT) and bone pressure and heat pain were assessed, respectively. The causality information was extracted from the EEG by phase slope index (PSI). Among the features...... being reproducible between the two baseline recordings, several PSI features were altered by remifentanil administration in comparison to placebo. Furthermore, several of the PSI features altered by remifentanil were correlated to changes in both CRT and pain scores. The results indicate...... that remifentanil administration influence the information flow between several brain areas. Hence, the EEG causality approach offers the potential to assist in deciphering the cortical effects of remifentanil administration....

Hyperalgesia and temporal summation of pain after heat injury in man

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Pedersen, J L; Andersen, O K; Arendt-Nielsen, L

1998-01-01

of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury......, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia...... was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P heat injury. The pain threshold to single electrical stimuli was reduced...

Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

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Saloman, Jami L.

Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand

Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats.

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Chang, Lu; Ye, Fang; Luo, Quehua; Tao, Yuanxiang; Shu, Haihua

2018-01-01

Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1-7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1-4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the

Remifentanil versus Sufentanil em infusão contínua em intervenções cirúrgicas videolaparoscópicas: estudo comparativo Remifentanil versus sufentanil en infusión continua en intervenciones quirúrgicas videolaparoscópicas: estudio comparativo Continuous infusion of remifentanil versus sufentanil in videolaparoscopic surgeries: a comparative study

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Ricardo Francisco Simoni

2008-06-01

cirugía, mientras que la IC de sufentanil 20 minutos antes. Los pacientes recibieron en el intraoperatorio cetoprofeno y dipirona. Como analgésico de rescate en la sala de recuperación pos anestésica (SRPA se usó el tramadol. Fueron analizadas las variaciones de la PAM y FC, tiempo de despertar, consumo de propofol, intercurrencias en la SRPA y tiempo de permanencia en la SRPA. RESULTADOS: El promedio de la PAM fue mayor en el GS con relación al GR (91,9 × 77,6, p BACKGROUND AND OBJECTIVES: Continuous infusion (CI of remifentanil is common in total intravenous anesthesia. On the other hand, CI of sufentanil for short/medium-term surgeries has not been widely used. The objective of this study was to compare two techniques of total intravenous anesthesia, using CI of remifentanil or sufentanil, regarding their intraoperative behavior and characteristics of recovery of patients undergoing videolaparoscopic surgeries. METHODS: Sixty patients, equally divided in 2 groups (RG and SG, participated in this study. Continuous infusion of remifentanil was used for anesthetic induction in RG, while a bolus of sufentanil associated with CI of this drug was used in SG. The CI of remifentanil was discontinued at the end of the surgery, while the CI of sufentanil was discontinued 20 minutes before the end of the surgery. Patients received ketoprofen and dypirone intraoperatively. Tramadol was used for rescue analgesia in the recovery room. Variations of mean arterial pressure (MAP and hard reate (HR, time for awakening, propofol consumption, intercurrences in the recovery room, and time of stay in the recovery room were analyzed. RESULTS: Mean MAP was greater in SG than in RG (91.9 × 77.6, p < 0.0001. The incidence of pain was significantly greater in RG than on SG (22 × 1 patient, p < 0.0001. The incidence of postoperative nausea and vomiting (PONV was greater in RG than in SG (10 × 2 patients, p < 0.0098. The mean time of stay in the recovery room was greater in RG than in

Bone hyperalgesia after mechanical impact stimulation: a human experimental pain model.

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Finocchietti, Sara; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

2014-12-01

Hyperalgesia in different musculoskeletal structures including bones is a major clinical problem. An experimental bone hyperalgesia model was developed in the present study. Hyperalgesia was induced by three different weights impacted on the shinbone in 16 healthy male and female subjects. The mechanical impact pain threshold (IPT) was measured as the height from which three weights (165, 330, and 660 g) should be dropped to elicit pain at the shinbone. Temporal summation of pain to repeated impact stimuli was assessed. All these stimuli caused bone hyperalgesia. The pressure pain threshold (PPT) was assessed by a computerized pressure algometer using two different probes (1.0 and 0.5 cm(2)). All parameters were recorded before (0), 24, 72, and 96 h after the initial stimulations. The IPTs were lowest 24 h after hyperalgesia induction for all three weights and the effect lasted up to 72 h (p pain and hyperalgesia model may provide the basis for studying this fundamental mechanism of bone-related hyperalgesia and be used for profiling compounds developed for this target.

Remifentanil-induced spike activity as a diagnostic tool in epilepsy surgery

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Gronlykke, L.; Knudsen, M.L.; Hogenhaven, H.

2008-01-01

. Electrocorticography (ECoG) recordings were performed on the intraventricular hippocampus and from the anterior inferior temporal and lateral neocortex before and after a 300 microg intravenous bolus of remifentanil. Spike activity was quantified as spike-count per minute. RESULTS: A significant increase (P

Comparison of the effects of remifentanil and remifentanil plus lidocaine on intubation conditions in intellectually disabled patients

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Can Eyigor

2014-07-01

Full Text Available BACKGROUND AND OBJECTIVES: This is a prospective, randomized, single-blind study. We aimed to compare the tracheal intubation conditions and hemodynamic responses either remifentanil or a combination of remifentanil and lidocaine with sevoflurane induction in the absence of neuromuscular blocking agents. METHODS: Fifty intellectually disabled, American Society of Anesthesiologists I-II patients who underwent tooth extraction under outpatient general anesthesia were included in this study. Patients were randomized to receive either 2 μg kg-1 remifentanil (Group 1, n = 25 or a combination of 2 μg kg-1 remifentanil and 1 mg kg-1 lidocaine (Group 2, n = 25. To evaluate intubation conditions, Helbo-Hansen scoring system was used. In patients who scored 2 points or less in all scorings, intubation conditions were considered acceptable, however if any of the scores was greater than 2, intubation conditions were regarded unacceptable. Mean arterial pressure, heart rate and peripheral oxygen saturation (SpO2 were recorded at baseline, after opioid administration, before intubation, and at 1, 3, and 5 min after intubation. RESULTS: Acceptable intubation parameters were achieved in 24 patients in Group 1 (96% and in 23 patients in Group 2 (92%. In intra-group comparisons, the heart rate and mean arterial pressure values at all-time points in both groups showed a significant decrease compared to baseline values (p = 0.000 CONCLUSION: By the addition of 2 μg/kg remifentanil during sevoflurane induction, successful tracheal intubation can be accomplished without using muscle relaxants in intellectually disabled patients who undergo outpatient dental extraction. Also worth noting, the addition of 1 mg/kg lidocaine to 2 μg/kg remifentanil does not provide any additional improvement in the intubation parameters.

Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model.

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Larsen, Malte Selch; Keizer, Ron; Munro, Gordon; Mørk, Arne; Holm, René; Savic, Rada; Kreilgaard, Mads

2016-05-01

Gabapentin displays non-linear drug disposition, which complicates dosing for optimal therapeutic effect. Thus, the current study was performed to elucidate the pharmacokinetic/pharmacodynamic (PKPD) relationship of gabapentin's effect on mechanical hypersensitivity in a rat model of CFA-induced inflammatory hyperalgesia. A semi-mechanistic population-based PKPD model was developed using nonlinear mixed-effects modelling, based on gabapentin plasma and brain extracellular fluid (ECF) time-concentration data and measurements of CFA-evoked mechanical hyperalgesia following administration of a range of gabapentin doses (oral and intravenous). The plasma/brain ECF concentration-time profiles of gabapentin were adequately described with a two-compartment plasma model with saturable intestinal absorption rate (K m  = 44.1 mg/kg, V max  = 41.9 mg/h∙kg) and dose-dependent oral bioavailability linked to brain ECF concentration through a transit compartment. Brain ECF concentration was directly linked to a sigmoid E max function describing reversal of hyperalgesia (EC 50, plasma  = 16.7 μg/mL, EC 50, brain  = 3.3 μg/mL). The proposed semi-mechanistic population-based PKPD model provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides reasonable predictions of clinically effective plasma concentrations for gabapentin.

Vascular endothelial cells mediate mechanical stimulation-induced enhancement of endothelin hyperalgesia via activation of P2X2/3 receptors on nociceptors.

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Joseph, Elizabeth K; Green, Paul G; Bogen, Oliver; Alvarez, Pedro; Levine, Jon D

2013-02-13

Endothelin-1 (ET-1) is unique among a broad range of hyperalgesic agents in that it induces hyperalgesia in rats that is markedly enhanced by repeated mechanical stimulation at the site of administration. Antagonists to the ET-1 receptors, ET(A) and ET(B), attenuated both initial as well as stimulation-induced enhancement of hyperalgesia (SIEH) by endothelin. However, administering antisense oligodeoxynucleotide to attenuate ET(A) receptor expression on nociceptors attenuated ET-1 hyperalgesia but had no effect on SIEH, suggesting that this is mediated via a non-neuronal cell. Because vascular endothelial cells are both stretch sensitive and express ET(A) and ET(B) receptors, we tested the hypothesis that SIEH is dependent on endothelial cells by impairing vascular endothelial function with octoxynol-9 administration; this procedure eliminated SIEH without attenuating ET-1 hyperalgesia. A role for protein kinase Cε (PKCε), a second messenger implicated in the induction and maintenance of chronic pain, was explored. Intrathecal antisense for PKCε did not inhibit either ET-1 hyperalgesia or SIEH, suggesting no role for neuronal PKCε; however, administration of a PKCε inhibitor at the site of testing selectively attenuated SIEH. Compatible with endothelial cells releasing ATP in response to mechanical stimulation, P2X(2/3) receptor antagonists eliminated SIEH. The endothelium also appears to contribute to hyperalgesia in two ergonomic pain models (eccentric exercise and hindlimb vibration) and in a model of endometriosis. We propose that SIEH is produced by an effect of ET-1 on vascular endothelial cells, sensitizing its release of ATP in response to mechanical stimulation; ATP in turn acts at the nociceptor P2X(2/3) receptor.

Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

DEFF Research Database (Denmark)

Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars

2000-01-01

We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments....... Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following...... were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced...

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

Science.gov (United States)

Baron, R; Wasner, G; Borgstedt, R; Hastedt, E; Schulte, H; Binder, A; Kopper, F; Rowbotham, M; Levine, J D; Fields, H L

1999-03-23

Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

Remifentanil maintains lower initial delayed nonmatching-to-sample accuracy compared to food pellets in male rhesus monkeys.

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Hutsell, Blake A; Banks, Matthew L

2017-12-01

Emerging human laboratory and preclinical drug self-administration data suggest that a history of contingent abused drug exposure impairs performance in operant discrimination procedures, such as delayed nonmatching-to-sample (DNMTS), that are hypothesized to assess components of executive function. However, these preclinical discrimination studies have exclusively used food as the reinforcer and the effects of drugs as reinforcers in these operant procedures are unknown. The present study determined effects of contingent intravenous remifentanil injections on DNMTS performance hypothesized to assess 1 aspect of executive function, working memory. Daily behavioral sessions consisted of 2 components with sequential intravenous remifentanil (0, 0.01-1.0 μg/kg/injection) or food (0, 1-10 pellets) availability in nonopioid dependent male rhesus monkeys (n = 3). Remifentanil functioned as a reinforcer in the DNMTS procedure. Similar delay-dependent DNMTS accuracy was observed under both remifentanil- and food-maintained components, such that higher accuracies were maintained at shorter (0.1-1.0 s) delays and lower accuracies approaching chance performance were maintained at longer (10-32 s) delays. Remifentanil maintained significantly lower initial DNMTS accuracy compared to food. Reinforcer magnitude was not an important determinant of DNMTS accuracy for either remifentanil or food. These results extend the range of experimental procedures under which drugs function as reinforcers. Furthermore, the selective remifentanil-induced decrease in initial DNMTS accuracy is consistent with a selective impairment of attentional, but not memorial, processes. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Anesthesia recovery comparison between remifentanil-propofol and remifentanil-desflurane guided by Bispectral Index® monitoring

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Raphael Grossi Rocha

2017-09-01

Full Text Available Background and objectives: There is a strong demand for fast and predictable anesthesia recovery with few side effects. Choice of the hypnotic agent could impact on that. This study investigated the differences between recoveries after remifentanil-propofol and remifentanil-desflurane anesthesias guided by bispectral index (BIS®. Methods: Forty patients were randomly assigned into 2 groups according to the anesthesia technique applied: remifentanil-propofol (REM-PRO and remifentanil-desflurane (REM-DES. After the discontinuation of the anesthetics, the times to extubation, to obey commands and to recover the airway protection reflex were recorted. In the post-anesthetic recovery room (PACU it was recorded the occurrence of nausea and vomiting (PONV, scores of Ramsay sedation scale and of numeric pain scale (NPS, morphine dose and length of stay in the unit. Results: Data from 38 patients were analyzed: 18 from REM-PRO and 20 from REM-DES group. Anesthesia times were similar (REM-PRO = 193 min, SD 79.9 vs. 175.7 min, SD 87.9 REM-DES; p = 0.5. REM-DES had shorter times than REM-PRO group: time to follow command (8.5 min; SD 3.0 vs. 5.6 min; SD 2.5; p = 0.0 and extubation time (6.2 min; 3.1–8.5 vs. 9.5 min; 4.9–14.4; p = 0.0. Times to recover airway protective reflex were similar: 16 patients from REM-PRO (88.9% restored the airway protective reflex 2 min after extubation vs. 17 from REM-DES (89.5%; and 2 patients from REM-PRO (11.1% vs. 2 from REM-DES (10.5% 6 min after extubation, p = 1. Ramsay sedation score, NPS, PONV incidents, morphine dose and PACU stay of length PACU were also similar. Conclusion: Remifentanil-desflurane-based anesthesia has a faster extubation time and to follow command than remifentanil-propofol-based anesthesia when both guided by BIS®. Resumo: Justificativa e objetivos: Há uma forte demanda por recuperação pós-anestésica rápida e previsível com poucos efeitos adversos. A escolha do agente

Tratamento farmacológico da hiperalgesia experimentalmente induzida pelo núcleo pulposo Pharmacologic treatment of hyperalgesia experimentally induced by nucleus pulposus

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André Luiz de Souza Grava

2010-01-01

Full Text Available OBJETIVO: Avaliar o efeito de drogas anti-inflamatórias (dexametasona, indometacina, atenolol, indometacina e atenolol e analgésica (morfina sobre a hiperalgesia experimentalmente induzida pelo núcleo pulposo em contato com o gânglio da raiz dorsal de L5. MÉTODOS: Trinta ratos Wistar machos com peso de 220 a 250g foram utilizados no estudo. A indução da hiperalgesia foi realizada por meio do contato de fragmento de núcleo pulposo retirado da região sacrococcígea e colocado sobre o gânglio da raiz dorsal de L5. Os 30 animais foram divididos em grupos experimentais de acordo com a droga utilizada. As drogas foram administradas durante duas semanas a partir da realização do procedimento cirúrgico para a indução da hiperalgesia. A hiperalgesia mecânica e térmica foram avaliadas por meio do teste da pressão constante da pata, von Frey eletrônico e Hargraves por um período de sete semanas. RESULTADOS: A maior redução da hiperalgesia foi observada no grupo de animais tratados pela morfina, seguido pela dexametasona, indometacina e atenolol. A redução da hiperalgesia foi observada após a interrupção da administração das drogas, com exceção do grupo de animais tratados com morfina, nos quais ocorreu aumento da hiperalgesia após a interrupção do tratamento. CONCLUSÕES: A hiperalgesia induzida pelo contato do núcleo pulposo com o gânglio da raiz dorsal pode ser reduzida com a administração de anti-inflamatórios e analgésicos, tendo sido observado a maior redução da hiperalgesia com a administração da morfina e dexametasona.OBJECTIVE: To evaluate the effect of antiinflammatory (dexamethasone, indomethacin, atenolol, indomethacin and atenolol and analgesic drugs (morphine on hyperalgesia experimentally induced by nucleus pulposus (NP contact with the L5- dorsal root ganglion (DRG. METHODS: Thirty male Wistar rats with weights ranging from 220 to 250 g were used in the study. The hyperalgesia was induced by

Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice

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Carlton Susan M

2010-03-01

Full Text Available Abstract Background Cisplatin is primarily used for treatment of ovarian and testicular cancer. Oxaliplatin is the only effective treatment for metastatic colorectal cancer. Both are known to cause dose related, cumulative toxic effects on the peripheral nervous system and thirty to forty percent of cancer patients receiving these agents experience painful peripheral neuropathy. The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain. Results In this study, using real-time, reverse transcriptase, polymerase chain reaction (RT-PCR, we analyzed the expression of TRPV1, TRPM8, and TRPA1 induced by cisplatin or oxaliplatin in vitro and in vivo. For in vitro studies, cultured E15 rat dorsal root ganglion (DRG neurons were treated for up to 48 hours with cisplatin or oxaliplatin. For in vivo studies, trigeminal ganglia (TG were isolated from mice treated with platinum drugs for three weeks. We show that cisplatin and oxaliplatin-treated DRG neurons had significantly increased in TRPV1, TRPA1, and TRPM8 mRNA expression. TG neurons from cisplatin treated mice had significant increases in TRPV1 and TRPA1 mRNA expression while oxaliplatin strongly induced only TRPA1. Furthermore, compared to the cisplatin-treated wild-type mice, cisplatin-treated TRPV1-null mice developed mechanical allodynia but did not exhibit enhancement of noxious heat- evoked pain responses. Immunohistochemistry studies showed that cisplatin-treated mice had no change in the proportion of the TRPV1 immunopositive TG neurons. Conclusion These results indicate that TRPV1 and TRPA1 could contribute to the development of thermal hyperalgesia and mechanical allodynia following cisplatin-induced painful neuropathy but that TRPV1 has a crucial role in cisplatin-induced thermal hyperalgesia in vivo.

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

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Sandeep Devabhakthuni

2013-01-01

Full Text Available The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects.

Assessment of different anesthesia depth under total intravenous anesthesia on postoperative cognitive function in laparoscopic patients

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Delin Zhang

2016-01-01

Full Text Available Background: This study aimed to compare the effects of different depths of sedation during total intravenous anesthesia (TIVA with remifentanil and propofol given by target-controlled infusion (TCI on postoperative cognitive function in young and middle-aged patients undergoing gynecological laparoscopic surgery. Materials and Methods: A total of 150 American Society of Anesthesiologists physical Status I/II patients scheduled for gynecological laparoscopic operation were randomly divided into three groups. Anesthesia was maintained with intravenous infusion of TCI propofol and remifentanil, intermittent injected intravenously with rocuronium. The infusion concentration of propofol and remifentanil was adjusted to maintain bispectral index (BIS at 30 24 sores on the day before anesthesia and the day after surgery in all three groups. However, the first group had the significantly higher MMSE scores than the other two groups after surgery (P < 0.05. Compared with that before anesthesia, TMT completion time was shorter on the day after surgery in the first group, while prolonged in the third group (P < 0.05. The first group had the significantly lower TMT completion time than the other two groups (P < 0.05. Conclusion: The depth of sedation, 30 < BIS value ≤ 40, under TIVA with remifentanil and propofol given by TCI had the minimal influence on postoperative cognitive function.

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice.

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Chen, Yong; Boettger, Michael K; Reif, Andreas; Schmitt, Angelika; Uçeyler, Nurcan; Sommer, Claudia

2010-03-02

Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1beta), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1beta. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1beta, and IL-10 following CFA, overall corroborating the inhibitor data. These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

Visceral hyperalgesia induced by forebrain-specific suppression of native Kv7/KCNQ/M-current in mice

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Bian Xiling

2011-10-01

Full Text Available Abstract Background Dysfunction of brain-gut interaction is thought to underlie visceral hypersensitivity which causes unexplained abdominal pain syndromes. However, the mechanism by which alteration of brain function in the brain-gut axis influences the perception of visceral pain remains largely elusive. In this study we investigated whether altered brain activity can generate visceral hyperalgesia. Results Using a forebrain specific αCaMKII promoter, we established a line of transgenic (Tg mice expressing a dominant-negative pore mutant of the Kv7.2/KCNQ2 channel which suppresses native KCNQ/M-current and enhances forebrain neuronal excitability. Brain slice recording of hippocampal pyramidal neurons from these Tg mice confirmed the presence of hyperexcitable properties with increased firing. Behavioral evaluation of Tg mice exhibited increased sensitivity to visceral pain induced by intraperitoneal (i.p. injection of either acetic acid or magnesium sulfate, and intracolon capsaicin stimulation, but not cutaneous sensation for thermal or inflammatory pain. Immunohistological staining showed increased c-Fos expression in the somatosensory SII cortex and insular cortex of Tg mice that were injected intraperitoneally with acetic acid. To mimic the effect of cortical hyperexcitability on visceral hyperalgesia, we injected KCNQ/M channel blocker XE991 into the lateral ventricle of wild type (WT mice. Intracerebroventricular injection of XE991 resulted in increased writhes of WT mice induced by acetic acid, and this effect was reversed by co-injection of the channel opener retigabine. Conclusions Our findings provide evidence that forebrain hyperexcitability confers visceral hyperalgesia, and suppression of central hyperexcitability by activation of KCNQ/M-channel function may provide a therapeutic potential for treatment of abdominal pain syndromes.

Patient controlled remifentanil and epidural analgesia during labour : satisfaction, costs and safety

NARCIS (Netherlands)

Freeman, Liv

2016-01-01

Epidural analgesia provided superior analgesia to remifentanil PCA. Women randomised to epidural analgesia with a request for pain relief are more satisfied with their analgesia than women randomised to remifentanil PCA. Costs of epidural analgesia and remifentanil PCA are not significantly

Effects of the addition of remifentanil to propofol anesthesia on seizure length and postictal suppression index in electroconvulsive therapy.

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Porter, Richard; Booth, David; Gray, Hamish; Frampton, Chris

2008-09-01

Propofol is a widely used anesthetic agent for electroconvulsive therapy (ECT). However, there are concerns that its anticonvulsant effect may interfere with the efficacy of ECT. We aimed to investigate the effects on seizure activity of the addition of the opiate remifentanil to propofol anesthesia for ECT. A retrospective analysis of 633 treatments in 73 patients was conducted. At each treatment, patients had received anesthesia with propofol alone or propofol plus remifentanil, depending on which anesthetist was providing anesthesia. Analysis of variance was performed to examine the effects of the anesthetic used, the electrode placement, the dose of electricity administered, and the stage in the course of treatment. Dependent variables were electroencephalogram seizure length and postictal suppression index (PSI). Addition of remifentanil resulted in a small but significantly lower dose of propofol being used to induce unconsciousness. Addition of remifentanil affected seizure length, mainly related to an effect when placement was right unilateral (F = 5.70; P = 0.017). There was also a significantly increased PSI (F = 4.3; P = 0.039), which was not dependent on dose or on placement. The data suggest that addition of remifentanil to propofol anesthesia significantly alters seizure indices. This may be secondary to a reduction in the amount of propofol required or to an independent effect of remifentanil. The increase in PSI in particular suggests that addition of remifentanil may improve clinical response. However, this can only be examined in a randomized controlled trial.

The BDNF/TrkB signaling pathway is involved in heat hyperalgesia mediated by Cdk5 in rats.

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Hong-Hai Zhang

Full Text Available Cyclin-dependent kinase 5 (Cdk5 has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA via the brain-derived neurotrophic factor (BDNF-tyrosine kinase B (TrkB signaling pathway in the dorsal horn of the spinal cord in rats.Heat hyperalgesia induced by peripheral injection of CFA was significantly reversed by roscovitine, TrkB-IgG, and the TrkB inhibitor K252a, respectively. Furthermore, BDNF was significantly increased from 0.5 h to 24 h after CFA injection in the spinal cord dorsal horn. Intrathecal adminstration of the Cdk5 inhibitor roscovitine had no obvious effects on BDNF levels. Increased TrkB protein level was significantly reversed by roscovitine between 0.5 h and 6 h after CFA injection. Cdk5 and TrkB co-immunoprecipitation results suggested Cdk5 mediates the heat hyperalgesia induced by CFA injection by binding with TrkB, and the binding between Cdk5 and TrkB was markedly blocked by intrathecal adminstration of roscovitine.Our data suggested that the BDNF-TrkB signaling pathway was involved in CFA-induced heat hyperalgesia mediated by Cdk5. Roscovitine reversed the heat hyperalgesia induced by peripheral injection of CFA by blocking BDNF/TrkB signaling pathway, suggesting that severing the close crosstalk between Cdk5 and the BDNF/TrkB signaling cascade may present a potential target for anti-inflammatory pain.

Prediction of postoperative pain by preoperative nociceptive responses to heat stimulation

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Werner, Mads U; Duun, Preben; Kehlet, Henrik

2004-01-01

, secondary hyperalgesia area, thermal and mechanical pain perception, and pain thresholds. Postoperative analgesia consisted of ibuprofen and acetaminophen. Pain ratings (visual analog scale) at rest and during limb movement were followed for 10 days after surgery. RESULTS: The burn injury was associated......BACKGROUND: Despite major advances in the understanding of the neurobiologic mechanisms of pain, the wide variation in acute pain experience has not been well explained. Therefore, the authors investigated the potential of a preoperatively induced heat injury to predict subsequent postoperative...... pain ratings in patients undergoing knee surgery. METHODS: Twenty patients were studied. The burn injury was induced 6 days before surgery with a contact thermode (12.5 cm2, 47 degrees C for 7 min). The sensory testing, before and 1 h after the injury, included pain score during induction of the burn...

Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice

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Üçeyler Nurcan

2010-03-01

Full Text Available Abstract Background Although it has been largely demonstrated that nitric oxide synthase (NOS, a key enzyme for nitric oxide (NO production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results Intraperitoneal (i.p. pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor, aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor, L-N(G-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor, but not L-N(5-(1-iminoethyl-ornithine (L-NIO, a selective endothelial NOS inhibitor, significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl. injection of complete Freund's adjuvant (CFA. Real-time reverse transcription-polymerase chain reaction (RT-PCR revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF, interleukin-1 beta (IL-1β, and interleukin-10 (IL-10 gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1β. The increase of the anti-inflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO mice had lower gene expression of TNF, IL-1β, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.

Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index.

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Nieuwenhuijs, Diederik J F; Olofsen, Erik; Romberg, Raymonda R; Sarton, Elise; Ward, Denham; Engbers, Frank; Vuyk, Jaap; Mooren, Rene; Teppema, Luc J; Dahan, Albert

2003-02-01

Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error. A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction). These data show dose-dependent effects on respiration at relatively low concentrations of

Remifentanil Reduces Blood Loss During Orthognathic Surgery.

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Matsuura, Nobuyuki; Okamura, Taiki; Ide, Satoko; Ichinohe, Tatsuya

2017-01-01

Remifentanil is reported to reduce oral tissue blood flow. We performed a retrospective investigation using logistic regression analysis of anesthesia records to investigate whether the use of remifentanil infusion in a balanced anesthesia technique was useful as a primary technique to reduce blood loss during orthognathic surgery. Subjects were 80 patients who underwent Le Fort I osteotomy and sagittal split ramus osteotomy of the mandible. The variables included gender, age, weight, type of maintenance anesthetic, type and dose or infusion rate of opioid, mean systolic blood pressure (SBP-mean), coefficient of variation of systolic blood pressure (CVSBP) during surgery, mean heart rate (HR-mean), duration of surgery, total blood loss, volume of infusion used, amount of local anesthetic used, body temperature, and urine output. Gender, type of maintenance anesthetic, type of opioid, SBP-mean, CVSBP, HR-mean, and duration of surgery were used as candidates for independent variables. Logistic regression analysis was performed for the selected independent variables with the total blood loss as the dependent variable. The factors associated with the reduction of blood loss were the use of remifentanil (odds ratio, 3.112; 95% CI, 1.166-8.307; P = .023) and smaller CVSBP (odds ratio, 2.747; 95% CI, 1.07-7.053; P = .036). Use of remifentanil and smaller CVSBP were associated with a reduction of blood loss during orthognathic surgery.

Remifentanil: A help in topical strabismus surgery.

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Sánchez-Guillén, I; López, R; Calle, M A; Diez-Lobo, A B

2017-12-01

To analyze the analgesic effect of remifentanil, side effects and complications in topical strabismus surgery. To study the results of strabismus surgery with this type of anesthesia. Retrospective descriptive study. We included 39 patients undergoing strabismus surgery with topical anesthesia and analgesia-based sedation with remifentanil. The data of the anesthetic and surgical technique, surgical results and stability of the deviation angle were analyzed. Thirty nine patients (54% women) were included, the average age was 37,4years old. The mean follow-up was 24,5months. The preoperative diagnoses were exotropia (21 patients), esotropia (12), paresis strabismus (4) and Duane's Syndrome (2). 15% patients had preoperative diplopia and 13 had received previous treatments. The dose range of remifentanil used was 0.05 to 0.2μg/kg/min. The side effects presented were 2 cases of vomit and one of bad collaboration during the intraoperative adjustment, one of the patient reported pain and one case of thoracic rigidity was reported. 79% of the patients obtained a good surgical result and 82% reported being satisfied with the results. The reintervention rate was 5%. Analgesia-based sedation with remifentanil is an useful complement to topical strabismus surgery because it reduces pain during surgery and allows the patient to collaborate during intraoperative adjustment due to its pharmacokinetic characteristics. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

Gender differences in pain and secondary hyperalgesia after heat/capsaicin sensitization in healthy volunteers

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Jensen, Magnus Thorsten; Petersen, Karin Lottrup

2006-01-01

differences in development of secondary hyperalgesia. Cutaneous hyperalgesia was induced with the heat/capsaicin sensitization model. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation after heat and capsaicin sensitization, rating of pain during heat....../capsaicin sensitization, and heat pain detection thresholds. There was a trend toward smaller areas of secondary hyperalgesia in women. After adjusting for estimated gender differences in forearm surface area, areas to brush but not von Frey hair stimulation after capsaicin sensitization were larger in women. Peak pain......, but not total pain, during prolonged noxious thermal stimulation was higher in women. There was no gender difference in pain ratings during capsaicin sensitization or in heat pain detection thresholds. The results provided only limited support to the hypothesis that gender differences in clinical pain syndromes...

Intravenous remifentanil versus epidural ropivacaine with sufentanil for labour analgesia: a retrospective study.

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Rong Lin

Full Text Available Remifentanil with appropriate pharmacological properties seems to be an ideal alternative to epidural analgesia during labour. A retrospective cohort study was undertaken to assess the efficacy and safety of remifentanil intravenous patient-controlled analgesia (IVPCA compared with epidural analgesia. Medical records of 370 primiparas who received remifentanil IVPCA or epidural analgesia were reviewed. Pain and sedation scores, overall satisfaction, the extent of pain control, maternal side effects and neonatal outcome as primary observational indicators were collected. There was a significant decline of pain scores in both groups. Pain reduction was greater in the epidural group throughout the whole study period (0 ∼ 180 min (P < 0.0001, and pain scores in the remifentanil group showed an increasing trend one hour later. The remifentanil group had a lower SpO2 (P < 0.0001 and a higher sedation score (P < 0.0001 within 30 min after treatment. The epidural group had a higher overall satisfaction score (3.8 ± 0.4 vs. 3.7 ± 0.6, P = 0.007 and pain relief score (2.9 ± 0.3 vs. 2.8 ± 0.4, P < 0.0001 compared with the remifentanil group. There was no significant difference on side effects between the two groups, except that a higher rate of dizziness (1% vs. 21.8%, P < 0.0001 was observed during remifentanil analgesia. And logistic regression analysis demonstrated that nausea, vomiting were associated with oxytocin usage and instrumental delivery, and dizziness was associated to the type and duration of analgesia. Neonatal outcomes such as Apgar scores and umbilical-cord blood gas analysis were within the normal range, but umbilical pH and base excess of neonatus in the remifentanil group were significantly lower. Remifentanil IVPCA provides poorer efficacy on labor analgesia than epidural analgesia, with more sedation on parturients and a trend of newborn acidosis. Despite these adverse effects, remifentanil IVPCA can still be an alternative

[Characteristics of experimental occlusal interference-induced masticatory mechanical hyperalgesia of rats].

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Li, Xuejiao; Cao, Ye; Xie, Qiufei

2014-10-01

To investigate the relationship between the existence of occlusal interference and masticatory muscle hyperalgesia by exploring the stimulus-response relationship between the duration of occlusal interference and masticatory muscle mechanical withdrawal threshold. Occlusal interference with 0.4 mm-thick crowns on rat molars was removed under anaesthesia at 2, 3, 4, 5, and 6 d after wear, and masticatory muscle mechanical withdrawal threshold was tested at 1, 3, 5, 7, 10, 14, 21 and 28 d. Decreased mechanical withdrawal thresholds were detected in temporal muscles and masseter muscles on both sides following occlusal interference (P 0.05). No significant differences were detected between the contralateral side with the ipsilateral side (P occlusal interference at 5 d, and the existence of the occlusal interference is positively correlated with the duration of the mechanical hyperalgesia.

The neuromuscular effects of rocuronium under sevoflurane-remifentanil or propofol-remifentanil anesthesia: a randomized clinical comparative study in an Asian population.

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Lee, Sangseok; Ro, Young Jin; Koh, Won Uk; Nishiyama, Tomoki; Yang, Hong-Seuk

2016-08-22

We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population. A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 μg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 μg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography. The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population. UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012).

Variable transcriptional responsiveness of the P2X3 receptor gene during CFA-induced inflammatory hyperalgesia.

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Nuñez-Badinez, Paulina; Sepúlveda, Hugo; Diaz, Emilio; Greffrath, Wolfgang; Treede, Rolf-Detlef; Stehberg, Jimmy; Montecino, Martin; van Zundert, Brigitte

2018-05-01

The purinergic receptor P2X3 (P2X3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2X3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2X3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background, and/or epigenetics. In this study, we sought to get insights into the molecular mechanisms responsible for inflammatory hyperalgesia by determining P2X3-R expression in DRG neurons of juvenile male rats that received a Complete Freund's Adjuvant (CFA) bilateral paw injection. We demonstrate that all CFA-treated rats showed inflammatory hyperalgesia, however, only a fraction (14-20%) displayed increased P2X3-R mRNA levels, reproducible across both sides. Immunostaining assays did not reveal significant increases in the percentage of P2X3-positive neurons, indicating that increased P2X3-R at DRG somas is not critical for inducing inflammatory hyperalgesia in CFA-treated rats. Chromatin immunoprecipitation (ChIP) assays showed a correlated (R 2  = 0.671) enrichment of the transcription factor Runx1 and the epigenetic active mark histone H3 acetylation (H3Ac) at the P2X3-R gene promoter in a fraction of the CFA-treated rats. These results suggest that animal-specific increases in P2X3-R mRNA levels are likely associated with the genetic/epigenetic context of the P2X3-R locus that controls P2X3-R gene transcription by recruiting Runx1 and epigenetic co-regulators that mediate histone acetylation. © 2017 Wiley Periodicals, Inc.

Sphingosine 1-phosphate mediates hyperalgesia via a neutrophil-dependent mechanism.

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Amanda Finley

Full Text Available Novel classes of pain-relieving molecules are needed to fill the void between non-steroidal anti-inflammatory agents and narcotics. We have recently shown that intraplantar administration of sphingosine 1-phosphate (S1P in rats causes peripheral sensitization and hyperalgesia through the S1P(1 receptor subtype (S1PR(1: the mechanism(s involved are largely unknown and were thus explored in the present study. Intraplantar injection of carrageenan in rats led to a time-dependent development of thermal hyperalgesia that was associated with pronounced edema and infiltration of neutrophils in paw tissues. Inhibition of 1 S1P formation with SK-I, a sphingosine kinase inhibitor, 2 S1P bioavailability with the S1P blocking antibody Sphingomab, LT1002 (but not its negative control, LT1017 or 3 S1P actions through S1PR(1 with the selective S1PR(1 antagonist, W146 (but not its inactive enantiomer, W140 blocked thermal hyperalgesia and infiltration of neutrophils. Taken together, these findings identify S1P as an important contributor to inflammatory pain acting through S1PR(1 to elicit hyperalgesia in a neutrophil-dependant manner. In addition and in further support, we demonstrate that the development of thermal hyperalgesia following intraplantar injection of S1P or SEW2871 (an S1PR(1 agonist was also associated with neutrophilic infiltration in paw tissues as these events were attenuated by fucoidan, an inhibitor of neutrophilic infiltration. Importantly, FTY720, an FDA-approved S1P receptor modulator known to block S1P-S1PR(1 signaling, attenuated carrageenan-induced thermal hyperalgesia and associated neutrophil infiltration. Targeting the S1P/S1PR(1 axis opens a therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

Intubating conditions and side effects of propofol, remifentanil and sevoflurane compared with propofol, remifentanil and rocuronium: a randomised, prospective, clinical trial

Science.gov (United States)

2014-01-01

Background Tracheal intubation without muscle relaxants is usually performed with remifentanil and propofol or sevoflurane. Remifentanil 1.0 to 4.0 μg·kg-1 and propofol 2.0-3.0 mg·kg-1 or sevoflurane up to 8.0 Vol% provide acceptable, i.e. excellent or good intubating conditions. We hypothesized that sevoflurane 1.0 MAC would provide acceptable intubating conditions when combined with propofol and remifentanil. Methods Eighty-three patients to be intubated were randomised to two groups. The SEVO group received propofol 1.5 mg kg-1, remifentanil 0.30 μg kg min-1 and sevoflurane 1.0 MAC; the MR group received the same doses of propofol and remifentanil plus rocuronium 0.45 mg kg-1. We evaluated intubation and extubation conditions, mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). The vocal cords were examined for injury by videolaryngoscopy before and 24 hours after surgery. Results Acceptable intubating conditions were seen more frequently with rocuronium than with sevoflurane: 97% versus 82%; p = 0.03; the subscore for vocal cords was comparable: 100% versus 98%. MAP before intubation decreased significantly compared with the MAP at baseline to the same extent in both groups; ephedrine IV was given in 15 (SEVO) versus 16 (MR) patients; p = 0.93. BIS at tracheal intubation was 27 (13-65) in the SEVO group, 29 (14-62) in the MR group; p = 0.07. Vocal cord injuries (oedema, haematoma) were similar: 4 patients in each group. Conclusions Overall intubating conditions were better when rocuronium was used; the subscore for vocal cords was comparable. The incidence of side effects was the same in the two groups. Trial registration ClinicalTrials.Gov: NCT 01591031. PMID:24860256

A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition

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Huynh Truc

2007-12-01

Full Text Available Abstract Mechanical hyperalgesia is a clinically-relevant form of pain sensitization that develops through largely unknown mechanisms. TRPA1, a Transient Receptor Potential ion channel, is a sensor of pungent chemicals that may play a role in acute noxious mechanosensation and cold thermosensation. We have developed a specific small molecule TRPA1 inhibitor (AP18 that can reduce cinnameldehyde-induced nociception in vivo. Interestingly, AP18 is capable of reversing CFA-induced mechanical hyperalgesia in mice. Although TRPA1-deficient mice develop normal CFA-induced hyperalgeisa, AP18 is ineffective in the knockout mice, consistent with an on-target mechanism. Therefore, TRPA1 plays a role in sensitization of nociception, and that compensation in TRPA1-deficient mice masks this requirement.

Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.

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Otari, K V; Upasani, C D

2015-08-01

The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.

Comparative efficacy of Combination of Propofol or Thiopental with Remifentanil on Tracheal Intubation without Muscle Relaxants

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k Naseri

2007-10-01

remifentanil is better than thiopental and remifentanil for tracheal intubation without muscle relaxants, it induces more homodynamic changes.

Is mechanism and symptom-based analgesia an answer to opioid-Induced hyperalgesia?

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Mayank Gupta

2015-01-01

Full Text Available "Cancer Pain" and "Pain in cancer patient" are not synonymous. Opioid-induced Hyperalgesia (OIH is a paradoxical state of nociceptive sensitization caused by exposure to opioids. Neuropathic pain is only partially responsive to opioids; injudicious increase in dose of opioids in neuropathic pain may not only result in inadequate pain relief but also OIH. Majority of literature on OIH is in non-cancer pain with systemic use of opioids. We describe the development and successful treatment of OIH in a 55-year-old male patient with Small cell Carcinoma Lung. Opioid tapering, rotation, systemic desensitization helps in combatting OIH. The use of anti-neuropathic adjuvant analgesics helps not only in preventing and treating OIH but also in understanding putative mechanisms underlying neuropathic pain and OIH.

Spatial and temporal aspects of muscle hyperalgesia induced by nerve growth factor in humans

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Andersen, H.; Arendt-Nielsen, L.; Svensson, P.

2008-01-01

longus and at the web between 1st and 2nd metatarsal (central involvement). One day after the NGF/control injections, hypertonic saline (0.5 ml, 5.8%) was injected into the left and right TA to study the pain response to chemical stimulation of the hyperalgesic muscle tissue. Scores on a modified Likert...... distribution of muscle hyperalgesia over time (immediately after, 3 h, 1, 4, 7 and 21 days) after injecting NGF (5 mu g) into the tibialis anterior (TA) muscle, to explore possibly involved central pain mechanisms and to investigate the effect of gender on development of hyperalgesia. Totally 20 healthy...... scale were used to assess soreness during muscle function. An area of hyperalgesia was observed locally at the injected site 3 h after injection of NGF, which expanded both proximally and distally on day 1; this effect subsided on day 4. Decreased PPT was also found between 1st and 2nd metatarsal on day...

Fear of pain potentiates nocebo hyperalgesia

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Aslaksen PM

2015-10-01

Full Text Available Per M Aslaksen,1 Peter S Lyby2 1Department of Psychology, Research Group for Cognitive Neuroscience, The Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; 2Catosenteret Rehabilitation Center, Son, Norway Abstract: Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia. The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia. One hundred and eleven healthy volunteers (76 females participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain. Personality traits were measured by the Big-Five Inventory-10. Fear of pain was measured by the Fear of Pain Questionnaire III. Heat pain was induced by a PC-controlled thermode. Pain was measured by a computerized visual analog scale. Stress levels during the experiment were measured by numerical rating scales. The participants were randomized to a Nocebo group or to a no-treatment Natural History group. The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment. Mediation analysis showed that higher levels of the Fear of Pain Questionnaire III factor "fear of medical pain" significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses. There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect. The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain. Furthermore, measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality

A cortical source localization analysis of resting EEG data after remifentanil infusion

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Khodayari-Rostamabad, Ahmad; Graversen, Carina; Malver, Lasse P

2015-01-01

in several brain areas including inferior frontal gyrus and insula at frontal lobe oscillated more strongly after remifentanil infusion compared to placebo. Furthermore, the source activity at delta band was correlated with continuous reaction time index. CONCLUSIONS: These results indicate that alterations...... in brain oscillations during remifentanil are mostly localized to frontal, fronto-temporal and fronto-central lobes and related to cognitive function. SIGNIFICANCE: The approach offers the potential to be used for understanding the underlying mechanism of action of remifentanil on brain activity....

Neuroplastic alteration of TTX-resistant sodium channel with visceral pain and morphine-induced hyperalgesia

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Chen J

2012-11-01

Full Text Available Jinghong Chen,1,2,4 Ze-hui Gong,4 Hao Yan,2 Zhijun Qiao,3 Bo-yi Qin41Department of Internal Medicine, Neuroscience Program, The University of Texas Medical Branch, Galveston, TX, USA; 2The Divisions of Pharmacy, Pharmacology core lab, MD Anderson Cancer Center, Houston, TX, USA; 3University of Texas-Pan American, Edinburg, TX, USA; 4Beijing Institute of Pharmacology and Toxicology, Beijing, China Abstract: The discovery of the tetrodotoxin-resistant (TTX-R Na+ channel in nociceptive neurons has provided a special target for analgesic intervention. In a previous study we found that both morphine tolerance and persistent visceral inflammation resulted in visceral hyperalgesia. It has also been suggested that hyperexcitability of sensory neurons due to altered TTX-R Na+ channel properties and expression contributes to hyperalgesia; however, we do not know if some TTX-R Na+ channel property changes can be triggered by visceral hyperalgesia and morphine tolerance, or whether there are similar molecular or channel mechanisms in both situations. To evaluate the effects of morphine tolerance and visceral inflammation on the channel, we investigated the dorsal root ganglia (DRG neuronal change following these chronic treatments. Using whole-cell patch clamp recording, we recorded TTX-R Na+ currents in isolated adult rat lumbar and sacral (L6-S2 DRG neurons from normal and pathologic rats with colon inflammatory pain or chronic morphine treatment. We found that the amplitudes of TTX-R Na+ currents were signiflcantly increased in small-diameter DRG neurons with either morphine tolerance or visceral inflammatory pain. Meanwhile, the result also showed that those treatments altered the kinetics properties of the electrical current (ie, the activating and inactivating speed of the channel was accelerated. Our current results suggested that in both models, visceral chronic inflammatory pain and morphine tolerance causes electrophysiological changes in voltage

The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers

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Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

2016-01-01

, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min.), and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied. RESULTS: For areas of secondary hyperalgesia, an intra...... and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006). CONCLUSIONS: We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary...

The BDNF/TrkB Signaling Pathway Is Involved in Heat Hyperalgesia Mediated by Cdk5 in Rats

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Zhang, Hong-Hai; Zhang, Xiao-Qin; Xue, Qing-Sheng; Yan-Luo,; Huang, Jin-Lu; Zhang, Su; Shao, Hai-Jun; Lu, Han; Wang, Wen-Yuan; Yu, Bu-Wei

2014-01-01

Background Cyclin-dependent kinase 5 (Cdk5) has been shown to play an important role in mediating inflammation-induced heat hyperalgesia. However, the underlying mechanism remains unclear. The aim of this study was to determine whether roscovitine, an inhibitor of Cdk5, could reverse the heat hyperalgesia induced by peripheral injection of complete Freund's adjuvant (CFA) via the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling pathway in the dorsal horn of the spin...

Heat pain detection threshold is associated with the area of secondary hyperalgesia following brief thermal sensitization

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Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

2017-01-01

INTRODUCTION: The area of secondary hyperalgesia following brief thermal sensitization (BTS) of the skin and heat pain detection thresholds (HPDT) may both have predictive abilities in regards to pain sensitivity and clinical pain states. The association between HPDT and secondary hyperalgesia......, however, remains unsettled, and the dissimilarities in physiologic properties suggest that they may represent 2 distinctively different pain entities. The aim of this study was to investigate the association between HPDT and BTS-induced secondary hyperalgesia. METHODS: A sample of 121 healthy male...... participants was included and tested on 2 separate study days with BTS (45°C, 3 minutes), HPDT, and pain during thermal stimulation (45°C, 1 minute). Areas of secondary hyperalgesia were quantified after monofilament pinprick stimulation. The pain catastrophizing scale (PCS) and hospital anxiety and depression...

Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour

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Weibel, Stephanie; Jelting, Yvonne; Afshari, Arash

2017-01-01

trial sequential analysis. We included total zero event trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta-analysis. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: Twenty RCTs......) (all study arms included zero events, two trials, low-quality evidence). In one trial of remifentanil (PCA) versus another opioid (IM) three out of 18 women in the remifentanil and none out of 18 in the control group had a respiratory depression (very low-quality evidence).There is no evidence...... opioid (IV) and compared to remifentanil (PCA, different regimen) both with zero events in all study arms (one trial, very-low quality evidence). In one trial of remifentanil (PCA) versus another opioid (PCA) none out of nine newborns in the remifentanil and three out of eight in the opioid (PCA) group...

Advanced oxidation protein products sensitized the transient receptor potential vanilloid 1 via NADPH oxidase 1 and 4 to cause mechanical hyperalgesia

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Ruoting Ding

2016-12-01

Full Text Available Oxidative stress is a possible pathogenesis of hyperalgesia. Advanced oxidation protein products (AOPPs, a new family of oxidized protein compounds, have been considered as a novel marker of oxidative stress. However, the role of AOPPs in the mechanism of hyperalgesia remains unknown. Our study aims to investigate whether AOPPs have an effect on hyperalgesia and the possible underlying mechanisms. To identify the AOPPs involved, we induced hyperalgesia in rats by injecting complete Freund’s adjuvant (CFA in hindpaw. The level of plasma AOPPs in CFA-induced rats was 1.6-fold in comparison with what in normal rats (P<0.05. After intravenous injection of AOPPs-modified rat serum albumin (AOPPs-RSA in Sprague-Dawley rats, the paw mechanical thresholds, measured by the electronic von Frey system, significantly declined. Immunofluorescence staining indicated that AOPPs increased expressions of NADPH oxidase 1 (Nox1, NADPH oxidase 4 (Nox4, transient receptor potential vanilloid 1 (TRPV1 and calcitonin gene-related peptide (CGRP in the dorsal root ganglia (DRG tissues. In-vitro studies were performed on primary DRG neurons which were obtained from both thoracic and lumbar DRG of rats. Results indicated that AOPPs triggered reactive oxygen species (ROS production in DRG neurons, which were significantly abolished by ROS scavenger N-acetyl-l-cysteine (NAC and small-interfering RNA (siRNA silencing of Nox1 or Nox4. The expressions of Nox1, Nox4, TRPV1 and CGRP were significantly increased in AOPPs-induced DRG neurons. And relevant siRNA or inhibitors notably suppressed the expressions of these proteins and the calcium influxes in AOPPs-induced DRG neurons. In conclusion, AOPPs increased significantly in CFA-induced hyperalgesia rats and they activated Nox1/Nox4-ROS to sensitize TRPV1-dependent Ca2+ influx and CGRP release which led to inducing mechanical hyperalgesia.

Intravenous Remifentanil versus Epidural Ropivacaine with Sufentanil for Labour Analgesia: A Retrospective Study

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Xu, Zhendong; Su, Jing; Liu, Zhiqiang

2014-01-01

Remifentanil with appropriate pharmacological properties seems to be an ideal alternative to epidural analgesia during labour. A retrospective cohort study was undertaken to assess the efficacy and safety of remifentanil intravenous patient-controlled analgesia (IVPCA) compared with epidural analgesia. Medical records of 370 primiparas who received remifentanil IVPCA or epidural analgesia were reviewed. Pain and sedation scores, overall satisfaction, the extent of pain control, maternal side effects and neonatal outcome as primary observational indicators were collected. There was a significant decline of pain scores in both groups. Pain reduction was greater in the epidural group throughout the whole study period (0∼180 min) (Panalgesia. And logistic regression analysis demonstrated that nausea, vomiting were associated with oxytocin usage and instrumental delivery, and dizziness was associated to the type and duration of analgesia. Neonatal outcomes such as Apgar scores and umbilical-cord blood gas analysis were within the normal range, but umbilical pH and base excess of neonatus in the remifentanil group were significantly lower. Remifentanil IVPCA provides poorer efficacy on labor analgesia than epidural analgesia, with more sedation on parturients and a trend of newborn acidosis. Despite these adverse effects, remifentanil IVPCA can still be an alternative option for labor analgesia under the condition of one-to-one bedside care, continuous monitoring, oxygen supply and preparation for neonatal resuscitation. PMID:25386749

Patient-controlled analgesia with remifentanil versus alternative parenteral methods for pain management in labour.

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Weibel, Stephanie; Jelting, Yvonne; Afshari, Arash; Pace, Nathan Leon; Eberhart, Leopold Hj; Jokinen, Johanna; Artmann, Thorsten; Kranke, Peter

2017-04-13

Multiple analgesic strategies for pain relief during labour are available. Recently remifentanil, a short-acting opioid, has recently been used as an alternative analgesic due to its unique pharmacological properties. To systematically assess the effectiveness of remifentanil intravenous patient-controlled analgesia (PCA) for labour pain, along with any potential harms to the mother and the newborn. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 December 2015), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), handsearched congress abstracts (November 2015), and reference lists of retrieved studies. Randomised controlled trials (RCTs) and cluster-randomised trials comparing remifentanil (PCA) with another opioid (intravenous (IV)/intramuscular (IM)), or with another opioid (PCA), or with epidural analgesia, or with remifentanil (continuous IV), or with remifentanil (PCA, different regimen), or with inhalational analgesia, or with placebo/no treatment in all women in labour including high-risk groups with planned vaginal delivery. Two review authors independently assessed trials for inclusion, extracted data, and appraised study quality.We contacted study authors for additional information other than incomplete outcome data. We performed random-effects meta-analysis.To reduce the risk of random error in meta-analysis we performed trial sequential analysis. We included total zero event trials and used a constant continuity correction of 0.01 (ccc 0.01) for meta-analysis. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of evidence. Twenty RCTs with 3569 women were included. Of those, 10 trials (2983 participants) compared remifentanil (PCA) to an epidural, four trials (216 participants) to another opioid (IV/IM), three trials (215 participants) to another opioid (PCA), two trials (135 participants) to remifentanil (continuous IV

Dextromethorphan attenuated the higher vulnerability to inflammatory thermal hyperalgesia caused by prenatal morphine exposure in rat offspring

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Chen Chien-Fang

2011-08-01

Full Text Available Abstract Background Co-administration of dextromethorphan (DM with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on inflammatory hyperalgesia in morphine-exposed offspring. Therefore, we attempt to investigate the possible effect of prenatal morphine exposure on the vulnerability to hyperalgesia and the possible therapeutic effect of DM in the present study. Methods Fifty μl of carrageenan (20 mg/ml was injected subcutaneously into the plantar surface of the right hind paw in p18 rats to induce hyperalgesia. Mean paw withdrawal latency was measured in the plantar test to index the severity of hyperalgesia. Using Western blotting and RT-PCR, the quantitative analyses of NMDA receptor NR1 and NR2B subunits were performed in spinal cords from different groups of animals. Results In the carrageenan-induced hyperalgesia model, rat offspring passively exposed to morphine developed a severe hyperalgesia on postnatal day 18 (p18, which also had a more rapid time course than those in the controls. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Western blot and RT-PCR analysis showed that the levels of protein and mRNA of NMDA receptor NR1 and NR2B subunits were significantly higher in the lumbar spinal cords of rats (p14 exposed to prenatal morphine; the co-administration of DM could reverse the effect of morphine on NR1 and attenuate the effect on NR2B. Conclusions Thus, DM may have a great potential in the prevention of higher vulnerability to inflammatory thermal hyperalgesia in the offspring of morphine-addicted mothers.

Flurbiprofen in rapid eye movement sleep deprivation induced hyperalgesia.

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Gürel, Elif Ezgi; Ural, Keremcan; Öztürk, Gülnur; Öztürk, Levent

2014-04-10

Rapid eye movement (REM) sleep deprivation induces hyperalgesia in healthy rats. Here, we evaluated the effects of flurbiprofen, an anti-inflammatory and neuroprotective agent, on the increased thermal responses observed in REM sleep deprived rats. Forty female rats were divided into four groups following 96-hour REM sleep deprivation: intraperitoneal injections of placebo, and flurbiprofen 5 mg/kg, 15 mg/kg and 40 mg/kg were made in CONT (n=10), FBP5, FBP15 and FBP40 groups respectively. Pain threshold measurements were performed three times at baseline (0.hour), at the end of REM sleep deprivation (96.hour) and at 1 h after injections (97.hour) by hot plate and tail-flick tests. REM sleep deprivation induced a significant decrease in pain thresholds of all rats (hotplate: 0.hour vs 96.hour, 9.75±2.85 vs 5.10±2.02, pFlurbiprofen in 15 mg/kg and 40 mg/kg doses significantly improved pain tolerance measured by tail flick test (tail flick in FBP15 and FBP40 groups: 96.hour vs 97.hour, 7.01±4.97 vs 8.34±3.61 and 5.06±1.57 vs 7.04±2.49, pFlurbiprofen was used for the first time in a rat model of REM sleep deprivation, and it provided anti-nociceptive effects in 15 mg/kg and 40 mg/kg doses. Flurbiprofen may have the potential for treatment of painful syndromes accompanying insomnia or sleep loss. Copyright © 2014 Elsevier Inc. All rights reserved.

Remifentanil versus placebo for analgesia during external cephalic version: a randomised clinical trial.

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Muñoz, H; Guerra, S; Perez-Vaquero, P; Valero Martinez, C; Aizpuru, F; Lopez-Picado, A

2014-02-01

Breech presentation occurs in up to 3% of pregnancies at term and may be an indication for caesarean delivery. External cephalic version can be effective in repositioning the fetus in a cephalic presentation, but may be painful for the mother. Our aim was to assess the efficacy of remifentanil versus placebo for pain relief during external cephalic version. A randomized, double-blind, controlled trial that included women at 36-41 weeks of gestation with non-cephalic presentations was performed. Women were randomized to receive either a remifentanil infusion at 0.1 μg/kg/min and demand boluses of 0.1 μg/kg, or saline placebo. The primary outcome was the numerical rating pain score (0-10) after external cephalic version. Sixty women were recruited, 29 in the control group and 31 in the remifentanil group. There were significant differences in pain scores at the end of the procedure (control 6.5 ± 2.4 vs. remifentanil 4.7 ± 2.5, P = 0.005) but not 10 min later (P = 0.054). The overall success rate for external cephalic version was 49% with no significant differences between groups (remifentanil group 54.8% vs. control group 41.3%, P = 0.358). In the remifentanil group, there was one case of nausea and vomiting, one of drowsiness and three cases of fetal bradycardia. In the control group, there were three cases of nausea and vomiting, one of dizziness and nine cases of fetal bradycardia. Intravenous remifentanil with bolus doses on demand during external cephalic version achieved a reduction in pain and increased maternal satisfaction. There were no additional adverse effects, and no difference in the success rate of external cephalic version or the incidence of fetal bradycardia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Remifentanil dose for laryngeal mask airway insertion with a single standard dose of propofol during emergency airway management in elderly patients.

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Ryu, Junghee; Oh, Ah Young; Baek, Ji-Seok; Kim, Jin-Hee; Park, Sang-Heon; Noh, Jae-Mun

2014-04-01

This study determined the dose of remifentanil to use during insertion of a Classic™ laryngeal mask airway (LMA, The Laryngeal Mask Co., Nicosia, Cyprus) in elderly patients during emergency airway management when combined with a single dose of propofol. Patients aged 65-80 years were enrolled. Anesthesia was induced with propofol 1 mg/kg, and then a blinded dose of remifentanil was infused over 30 s after confirming the patient's loss of consciousness. The dose of remifentanil was determined using Dixon's up-and-down method, starting at 0.5 µg/kg (a step size of 0.1 µg/kg). Insertion of the LMA was attempted 60 s after loss of consciousness. In total, 23 patients were recruited and the mean age ± standard deviation was 72 ± 3 years. The effective dose for successful LMA insertion in 50% of the patients (ED50) was 0.20 ± 0.05 µg/kg. No patient needed more than 0.3 µg/kg. Remifentanil 0.20 ± 0.05 µg/kg with propofol 1 mg/kg resulted in excellent LMA insertion in 50% of elderly patients without significant hemodynamic changes during emergency airway management.

Remifentanil vs. Lidocaine on Response to Tracheal Tube during Emergence of General Anesthesia

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Kambiz Sadegi

2014-08-01

Conclusion: we specified Remifentanil reduces cough during the emergence from general anesthesia more effective than Lidocaine in patients undergoing general surgery. In addition, Remifentanil and i.v. lidocaine revealed comparable impact regarding VAS scoring, sedation level and pethidine consumption.

Dynamic mechanical assessment of muscle hyperalgesia in humans: The dynamic algometer

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Finocchietti, Sara; Graven-Nielsen, Thomas; Arendt-Nielsen, Lars

2015-01-01

BACKGROUND: Musculoskeletal pain is often associated with a nonhomogeneous distribution of mechanical hyperalgesia. Consequently, new methods able to detect this distribution are needed. OBJECTIVE: To develop and test a new method for assessing muscle hyperalgesia with high temporal and spatial resolution that provides complementary information compared with information obtained by traditional static pressure algometry. METHODS: The dynamic pressure algometer was tested bilaterally on the tibialis anterior muscle in 15 healthy subjects and compared with static pressure algometry. The device consisted of a wheel that was rolled over the muscle tissue with a fixed velocity and different predefined forces. The pain threshold force was determined and pain intensity to a fixed-force stimulation was continuously rated on a visual analogue scale while the wheel was rolling over the muscle. The pressure pain sensitivity was evaluated before, during, and after muscle pain and hyperalgesia induced unilaterally by either injection of hypertonic saline (0.5 mL, 6%) into the tibialis anterior or eccentric exercise evoking delayed-onset muscle soreness (DOMS). RESULTS: The intraclass correlation coefficient was >0.88 for the dynamic thresholds; thus, the method was reliable. Compared with baseline, both techniques detected hyperalgesia at the saline injection site and during DOMS (Palgometer also detected the widespread, patchy distribution of sensitive loci during DOMS, which was difficult to evaluate using static pressure algometry. DISCUSSION AND CONCLUSION: The present study showed that dynamic pressure algometry is a reliable tool for evaluating muscle hyperalgesia (threshold and pain rating) with high temporal and spatial resolution. It can be applied as a simple clinical bed-side test and as a quantitative tool in pharmacological profiling studies. PMID:25664539

Intubation conditions in young infants after propofol and remifentanil induction with and without low-dose rocuronium.

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Gelberg, J; Kongstad, L; Werner, O

2014-08-01

Bolus injections of intravenous propofol and remifentanil can be used in the tracheal intubation of infants and children, but relatively large doses are needed. We hypothesised that addition of a small bolus of rocuronium would ensure good intubation conditions when modest propofol and remifentanil doses were used. Seventy infants between 3 weeks and 4 months of age were randomised to receive either placebo or rocuronium. Anaesthesia was induced with IV propofol, 3 (3-5) mg/kg [median (range)]. Rocuronium (0.2 mg/kg) or placebo was then injected, followed 15 s later by 2 μg/kg remifentanil. One anaesthetist attempted tracheal intubation 1 min after the rocuronium/placebo injection and used the 'Copenhagen scoring system' to assess intubation conditions. The neuromuscular effect of 0.2 mg/kg rocuronium was recorded in another eight, already intubated, infants using thumb accelerometry during train-of-four stimulation of the ulnar nerve. Intubation conditions were classified as 'poor' in 14 of 34 (41%) patients given placebo and in 10 of 36 (28%) patients given rocuronium (P = 0.32). There were four failed first attempts at intubation in the placebo group and none in the rocuronium group (P = 0.051). Maximum neuromuscular depression occurred 4 (3-8) after injection of 0.2 mg/kg rocuronium. Intubation conditions were poor in almost one third of the patients receiving propofol-remifentanil. Adding a low-dose rocuronium did not significantly improve intubation conditions. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia after acute foot trauma

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Tobias Wienemann

2014-11-01

Full Text Available Introduction and objective: Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy. Design and methods: A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture. Cases were 12 patients (11 diabetic subjects with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT and deep pressure pain perception threshold (DPPPT were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®. Results: In the control group, post-traumatic DPPPT (but not CPPPT at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group; CPPPT did not decrease post-operatively. Conclusion: Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma

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Wienemann, Tobias; Chantelau, Ernst A.; Koller, Armin

2014-01-01

Introduction and objective Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). Design and methods A case–control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II®). Results In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15–25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15–20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Conclusion Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to ‘pull away’ from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking. PMID:25397867

Effect of painless diabetic neuropathy on pressure pain hypersensitivity (hyperalgesia) after acute foot trauma.

Science.gov (United States)

Wienemann, Tobias; Chantelau, Ernst A; Koller, Armin

2014-01-01

Acute injury transiently lowers local mechanical pain thresholds at a limb. To elucidate the impact of painless (diabetic) neuropathy on this post-traumatic hyperalgesia, pressure pain perception thresholds after a skeletal foot trauma were studied in consecutive persons without and with neuropathy (i.e. history of foot ulcer or Charcot arthropathy). A case-control study was done on 25 unselected clinical routine patients with acute unilateral foot trauma (cases: elective bone surgery; controls: sprain, toe fracture). Cases were 12 patients (11 diabetic subjects) with severe painless neuropathy and chronic foot pathology. Controls were 13 non-neuropathic persons. Over 1 week after the trauma, cutaneous pressure pain perception threshold (CPPPT) and deep pressure pain perception threshold (DPPPT) were measured repeatedly, adjacent to the injury and at the opposite foot (pinprick stimulators, Algometer II(®)). In the control group, post-traumatic DPPPT (but not CPPPT) at the injured foot was reduced by about 15-25%. In the case group, pre- and post-operative CPPPT and DPPPT were supranormal. Although DPPPT fell post-operatively by about 15-20%, it remained always higher than the post-traumatic DPPPT in the control group: over musculus abductor hallucis 615 kPa (kilopascal) versus 422 kPa, and over metatarsophalangeal joint 518 kPa versus 375 kPa (medians; case vs. control group); CPPPT did not decrease post-operatively. Physiological nociception and post-traumatic hyperalgesia to pressure are diminished at the foot with severe painless (diabetic) neuropathy. A degree of post-traumatic hypersensitivity required to 'pull away' from any one, even innocuous, mechanical impact in order to avoid additional damage is, therefore, lacking.

A randomized trial of remifentanil for analgesia in external cephalic version for breech presentation.

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Liu, Xiaohua; Xue, Aiqin

2016-12-01

Although external cephalic version (ECV) can be effective for correcting the fetus in a cephalic presentation, it may be painful for the mother. This study aimed to evaluate the efficacy and safety of remifentanil for pain relief during ECV in China. In all, 152 Chinese parturients with singleton breech presentation were randomly divided into 2 groups, each with 76 patients. All 152 patients were assigned to receive either remifentanil (infused at 0.1 μg/kg/min and demand boluses of 0.1 μg/kg) or saline placebo. The study was performed between January 2012 and December 2015. Outcome measurements included the Numerical Rating Pain Scale score (0-10) after ECV, success rate for ECV, and maternal satisfaction after ECV. Adverse events were also evaluated. The study was completed by 146 patients. Remifentanil showed greater efficacy than placebo in decreasing the pain score immediately after ECV (remifentanil 4.6 ± 2.6 vs placebo 6.5 ± 2.7; P < 0.001). The success rate for ECV showed a significant difference between the 2 groups (remifentanil 56.5% vs placebo 39.5%; P = 0.04). Maternal satisfaction also showed a significant difference between the 2 groups (remifentanil 9.6 ± 1.4 vs placebo 6.4 ± 3.7; P < 0.001). However, the adverse events profiles were similar between both groups. The results of this study demonstrate that remifentanil is an effective intervention for reducing pain, achieving successful ECV, and increasing maternal satisfaction during ECV, and is generally well-tolerated without additional adverse effects.

[Inductions and intubating conditions with sevoflurane and different doses of remifentanil without muscle relaxant in children].

Science.gov (United States)

Wei, Ling-Xin; Deng, Xiao-Ming; Liu, Ju-Hui; Luo, Mao-Ping; Tong, Shi-Yi; Zhang, Yan-Ming; Liao, Xu; Xu, Kun-Lin

2008-12-01

To observe the clinical effectiveness of inductions and tracheal intubating conditions with 3% sevoflurane and different doses of remifentanil without muscle relaxant in children. Totally 120 peadiatric patients (aged 4-10 years, American Society of Anesthesiologists grade I for inhalational induction) were randomly allocated into group I (remifentanil 1 microg/kg), group II (remifentanil 2 microg/kg), group III (remifentanil 3 microg/kg), and control group (vecuronium bromide 0.1 mg/kg). After inhalational induction with 3% sevoflurane and 60% nitrous oxide in 40% oxygen for 2 minutes, remifentanil 1 microg/kg, 2 microg/ kg, and 3 microg/kg were intravenously injected over 1 minute into patients in group I , group II, and group III, respectively. After remifentanil administration and manual ventilation for 1 minute, the trachea was intubated. In the control group, 2 minutes after intravenous administration of vecuronium bromide 0.1 mg/kg, tracheal intubation was attempted. Agitation, intubating satisfactoriness, and the circulation changes after tracheal intubation and anesthesia induction were observed. In these four groups, agitation occurred in 37.5% of patients during sevoflurane induction. Satisfactory intubation rate was 70.0% in group I, 86.7% in group II, 90.0% in group III, and 93.3% in the control group. Compared with the control group, the impact of tracheal intubation on the circulatory system was smaller in group I , II , and III. Induction with 3% sevoflurane combined with remifentanil can be smoothly performed, followed by the successful tracheal intubation. The intubating conditions are more satisfactory with 3% sevoflurane combined with remifentanil 2 microg/kg or 3 microg/kg.

Comparison of remifentanil: Entonox with Entonox alone in labor analgesia

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Mojtaba Rahimi Varposhti

2013-01-01

Full Text Available Background: We designed a study to evaluate the effectiveness of continuous low dose infusion of remifentanil adding to self-administration of entonox administered for pain relief during the active phase of first stage of labor. Materials and Methods: Thirty healthy term pregnant women recruited in our randomized double-blind, cross over study. They received the study medicines during two 30-min periods with a 15-min wash-out sequence after each period. Fifteen parturient used remifentanil as a single bolus dose followed by constant low dose infusion and self-administration of entonox (group R during the first period and entonox and saline (group P during the second period, while the remainder of the parturient used the drugs in a reverse order. Pain and Ramsay score, maternal and fetal hemodynamic, and ventilation were assessed during each intervention. Results: In this study, mean pain severity scores were 8 ± 0.9 before and 5.4 ± 1.7 after intervention in group P, and 7.8 ± 0.1, 3.5 ± 1.3 in group R, respectively. Mean pain severity difference was 2.6 ± 1.5 in group P, while 4.3 ± 1.5 in group R; so, use of entonox and remifentanil can decrease labor pain two times more in comparison with entonox/placebo (normal saline. However, hemodynamic and ventilation parameter in remifentanil/entonox period were same as in entonox/placebo period. No statistical differences were seen in mean Ramsay score between group R and P. There was no episode of maternal bradycardia, hypotension, or hypoxemia. Conclusion: Not only adding low dose infusion of remifentanil to self-administration of entonox was notable in labor pain reduction, it did n′t make more parturient and neonatal side-effects.

Combination of dexmedetomidine and remifentanil for labor analgesia: A double-blinded, randomized, controlled study

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Waleed Abdalla

2015-01-01

Full Text Available Background: Satisfactory analgesia is of great importance in the labor. The clinical efficacy and side effects of remifentanil in the management of labor pain had been evaluated. Dexmedetomidine (DMET demonstrates an antinociceptive effect in visceral pain conditions. Aims of the study were to assess whether the combination of DMET with remifentanil would produce a synergistic effect that results in lower analgesic requirements. Furthermore, whether this combination would have less maternal and neonatal adverse effects. Patients and Methods: Sixty American Society of Anesthesiologists physical status I-II pregnant women had been enrolled into this study. All were full term (37-40 weeks′ gestation, singleton fetus with cephalic presentation in the first stage of spontaneous labor. They were divided into two groups group (I Patient-controlled IV remifentanil analgesia (bolus dose 0.25 μg/kg, lockout interval 2 min increased by 0.25 μg/kg to a maximum bolus dose 1 μg/kg in addition to a loading dose of DMET 1 μg/kg over 20 min, followed by infusion at 0.5 μg/kg/h group (II Patient-controlled IV remifentanil analgesia (PCA (bolus dose 0.25 μg/kg, lockout interval 2 min increased by 0.25 μg/kg to a maximum bolus dose 1 μg/kg in addition to a the same volume of normal saline as a loading dose, followed by a continuous saline infusion. Visual analog scale score, maternal, and fetal complications and patients′ satisfaction were recorded. Results: Patients receiving a combination of PCA remifentanil and DMET had a lower pain score compared with remifentanil alone in the second stage of labor (P = 0.001. The Total consumption of remifentanil was reduced by 53.3% in group I. There was an increased incidence of maternal complications and a lower patient satisfaction score in group II. Conclusion: DMET has an opioid sparing effect; a combination of DMET and remifentanil produces a synergistic effect that results in lower analgesic requirements

Remifentanil versus dexmedetomidina como coadjuvantes de técnica anestésica padronizada em pacientes com obesidade mórbida Remifentanil versus dexmedetomidina como coadyuvantes de técnica anestésica de modelo en pacientes con obesidad mórbida Remifentanil versus dexmedetomidine as coadjutants of standardized anesthetic technique in morbidly obese patients

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Eliana Cristina Murari Sudré

2004-04-01

ás 30% para ambas luego después de la intubación traqueal. Los pacientes fueron monitorizados con presión arterial media invasiva, oximetría de pulso, BIS, capnografia, estimulador de nervio periférico y electrocardiograma. Fueron evaluados: 1 diferentes tiempos de recuperación anestésica (abertura de los ojos, reinicio de la respiración espontanea, tiempo de extubación traqueal, tiempo para el alta de la sala de recuperación pos-anestésica y hospitalar, 2 la evolución de la gasometria arterial, y 3 analgesia pos-operatoria. RESULTADOS: Ochenta y ocho pacientes fueron evaluados. Los pacientes del grupo R presentaron abertura ocular mas precoz (9,49 ± 5,61 min versus 18,25 ± 10,24 min, p BACKGROUND AND OBJECTIVES: Two coadjuvant anesthetic drugs - remifentanil and dexmedetomidine - were compared in terms of anesthetic recovery, arterial pH and PaCO2 evolution, in morbidly obese patients submitted to Capella's surgery. METHODS: Participated in this prospective, randomized and double blind study 92 patients divided in two groups and submitted to standardized anesthetic technique (general/epidural. Remifentanil Group (Group R and Dexmedetomidine Group (Group D received continuous intravenous infusion of these drugs (0.1 µg.kg-1.min-1 and 0.5 µg.kg-1.h-1, ideal body weight plus 30% for both immediately after tracheal intubation. Monitoring consisted of invasive mean blood pressure, pulse oximetry, BIS EEG, capnography, peripheral nerve stimulator and EKG. The following parameters were evaluated: 1 different anesthetic recovery times (eye opening, return to spontaneous ventilation, tracheal extubation time, time for post anesthetic recovery unit and hospital discharge; 2 arterial blood gas analysis evolution; and 3 postoperative analgesia. RESULTS: Evaluation was possible in 88 patients. Patients group R had earlier eye opening (9.49 ± 5.61 min versus 18.25 ± 10.24 min, p < 0.0001, faster return to spontaneous ventilation (9.78 ± 5.80 min versus 16.58 ± 6

Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL-1 β and protein expression in spinal cord of mice.

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Piccinelli, Ana Claudia; Morato, Priscila Neder; Dos Santos Barbosa, Marcelo; Croda, Julio; Sampson, Jared; Kong, Xiangpeng; Konkiewitz, Elisabete Castelon; Ziff, Edward B; Amaya-Farfan, Jaime; Kassuya, Cândida Aparecida Leite

2017-04-01

We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. Male Swiss mice received gp120, IL-1β or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1β and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1β-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1β injection. These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1β and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1β application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1β emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences. Copyright © 2016. Published by Elsevier Inc.

Direct Effect of Remifentanil and Glycine Contained in Ultiva® on Nociceptive Transmission in the Spinal Cord: In Vivo and Slice Patch Clamp Analyses.

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Makoto Sumie

Full Text Available Ultiva® is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting μ-opioid receptor agonist. Ultiva® is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva® provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva® contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva® potentially complicates its effects. We examined how Ultiva® directly affects nociceptive transmission in the spinal cord.We made patch-clamp recordings from substantia gelatinosa (SG neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva® onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli.Bath application of Ultiva® hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs evoked by the stimuli was suppressed by Ultiva®. Miniature EPSCs (mEPSCs were depressed in frequency but not amplitude. Ultiva®-induced outward currents and suppression of mEPSCs were not inhibited by the μ-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva®-induced currents demonstrated a specific equilibrium potential similar to glycine.We found that intrathecal administration of Ultiva® to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva®-induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva® between intrathecal and intravenous

Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Hammer, J H; Moesgaard, F

1989-01-01

The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common...

Secondary hyperalgesia to heat stimuli after burn injury in man

DEFF Research Database (Denmark)

Pedersen, J L; Kehlet, H

1998-01-01

The aim of the study was to examine the presence of hyperalgesia to heat stimuli within the zone of secondary hyperalgesia to punctate mechanical stimuli. A burn was produced on the medial part of the non-dominant crus in 15 healthy volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min......), and assessments were made 70 min and 40 min before, and 0, 1, and 2 h after the burn injury. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain responses were rated with a visual analog scale (0-100). The area of secondary hyperalgesia...... to punctate stimuli was assessed with a rigid von Frey hair (462 mN). The heat pain responses to 45 degrees C in 5 s (3.75 cm2) were tested in the area just outside the burn, where the subjects developed secondary hyperalgesia, and on the lateral crus where no subject developed secondary hyperalgesia (control...

Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization?

DEFF Research Database (Denmark)

Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen

2016-01-01

role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated...... with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. METHODS AND DESIGN: We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii......) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate...

Remifentanil for the insertion and removal of long-term central venous access during monitored anesthesia care.

LENUS (Irish Health Repository)

Burlacu, Crina L

2012-02-01

STUDY OBJECTIVE: To determine the analgesic efficacy of three different rates of remifentanil infusion in patients undergoing insertion or removal of long-term central venous access devices during monitored anesthesia care and local anesthetic field infiltration. DESIGN: Double-blinded, randomized, controlled study. SETTING: Operating theatre of an University hospital. PATIENTS: 44 unpremedicated, ASA physical status 1 and 2 patients, aged 18-65 years, undergoing insertion or removal of a Port-a-Cath or Hickman catheter. INTERVENTIONS: Patients sedated with a propofol target-controlled infusion were randomly allocated to three groups: Group R25 (n = 14), Group R50 (n = 15), and Group R75 (n = 15), to receive remifentanil 0.025, 0.05, and 0.075 mug\\/kg\\/min, respectively. Rescue remifentanil 0.5 mug\\/kg was administered for pain scores > 3. The remifentanil infusion rate was maintained constant unless respiratory and\\/or cardiovascular unwanted events occurred, whereupon the rate was adjusted in 0.01 mug\\/kg\\/min decrements as necessary. MEASUREMENTS: Pain scores (primary outcome), sedation, and movement scores (secondary outcomes) were assessed during local anesthetic infiltration of the anterior chest wall and 5 other procedural steps. MAIN RESULTS: All infusion rates had equal analgesic efficacy, as shown by comparable pain scores, number of rescue boluses, and number of patients requiring rescue analgesia. Excessive sedation was associated with the highest remifentanil rate such that Group R75 patients were significantly more sedated than Groups R25 or R50 at selective procedural steps (P < 0.05). More Group R75 patients (6\\/15) required remifentanil rate reduction than did patients from Group R50 (1\\/15) or Group R25 (0\\/14), P < 0.01, most commonly because of respiratory depression. CONCLUSIONS: For the insertion or removal of long-term central venous access devices, all three remifentanil infusion rates proved to be equally analgesic

[Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane].

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Bischoff, P; Plümer, L; Scholz, J; Drögemeier, K; von Knobelsdorff, G; Schulte am Esch, J

1998-01-01

Electrophysiological parameters are well-suited to detect changes in cerebral function. The present study investigates whether balanced anaesthesia with remifentanil during nociceptive stimulation is associated with changes in clinical and electrophysiological parameters indicating inadequate depth of anaesthesia. Following IRB approval and written informed consent, 23 patients (ASA: I; age: 36 +/- 11) scheduled for elective gynaecological laparoscopy were included in the study. Without any premedication, anaesthesia was induced with remifentanil (1.0 microgram/kg bolus injection), propofol (0.5 mg/kg added by repetitive (10 mg) bolus injections every 10 s until unconciousness) and vecuronium (0.1 mg/kg). Following endotracheal intubation (normoventilation: PetCO2: 36 bis 38 mmHg), remifentanil infusion was started with continuous doses of 0.5 microgram/kg/min over 5 minutes and maintained with 0.25 microgram/kg/min during surgery. Remifentanil was randomly combined with propofol (group 1: 100 micrograms/kg/min; n = 7), enflurane (group 2: 0.5 MAC; n = 8) or isoflurane (group 3: 0.5 MAC; n = 8). Monitoring included: heart rate (beats/min), mean arterial pressure (mmHg), oxygen saturation (%), endtidal CO2 (mmHg) and endtidal enflurane and isoflurane (%). EEG: 2-channel recordings of Fz versus mastoid and ECG (artefact control) during steady-state anaesthesia and surgery. Following fast-fourier-transformation (4 s; 256/s; 0.5 to 35.0 Hz), spectral power densities were calculated for the selected frequency bands. Auditory evoked potentials (AEP; middle latency) were registered simultaneously after binaural stimulation via head-phones click-stimulation (6 Hz; 75 dB above hearing threshold; 512 stimulations per average). Bandpass was 0.01 to 2.0 kHz. Na, Pa, Nb (latencies; ms) and peak-to-peak amplitudes (NaPa, PaNb; microV). EEG and AEP recording technique [15]. The study protocol included baseline values from pre-intubation, pre-surgery, the respective post

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A prospective, double-blinded, randomised controlled trial.

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Morue, Hélène I; Raj-Lawrence, Shalini; Saxena, Sarah; Delbaere, Anne; Engelman, Edgard; Barvais, Luc A

2018-04-30

Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. Controlled, randomised, prospective, double-blinded study. The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. Of the 132 women undergoing oocyte retrieval included, 121 completed the study. After randomisation, patients received either a ketamine infusion (40 μg kg min over 5 min followed by 2.5 μg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is

Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

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Ohri, Rachit; Wang, Jeffrey Chi-Fei; Blaskovich, Phillip D; Pham, Lan N; Costa, Daniel S; Nichols, Gary A; Hildebrand, William P; Scarborough, Nelson L; Herman, Clifford J; Strichartz, Gary R

2013-09-01

Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the

Postoperative nausea and vomiting (PONV) in outpatient repair of inguinal hernia.

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Palumbo, Piergaspare; Usai, Sofia; Amatucci, Chiara; Pulli, Valentina Taurisano; Illuminati, Giulio; Vietri, Francesco; Tellan, Guglielmo

2018-01-01

Nausea and vomiting are among the most frequent complications following anesthesia and surgery. Due to anesthesia seems to be primarily responsible for post operative nausea and vomiting (PONV) in Day Surgery facilities, the aim of the study is to evaluate how different methods of anesthesia could modify the onset of postoperative nausea and vomiting in a population of patients undergoing inguinal hernia repair. Ninehundredten patients, aged between 18 and 87 years, underwent open inguinal hernia repair. The PONV risk has been assessed according to Apfel Score. Local anesthetic infiltration, performed by the surgeon in any cases, has been supported by and analgo-sedation with Remifentanil in 740 patients; Fentanyl was used in 96 cases and the last 74 underwent deep sedation with Propofol . Among the 910 patients who underwent inguinal hernia repair, PONV occurred in 68 patients (7.5%). Among patients presenting PONV, 29 received Remifentanil, whereas 39 received Fentanyl. In the group of patients receiving Propofol, no one presented PONV. This difference is statistically significant (p < .01). Moreover, only 50 patients of the total sample received antiemetic prophylaxis, and amongst these, PONV occurred in 3 subjects. Compared to Remifentanil, Fentanyl has a major influence in causing PONV. Nonetheless, an appropriate antiemetic prophylaxis can significantly reduce this undesirable complication. Key words: Day Surgery, Fentanyl, Inguinal, Hernia repair, Nausea, Vomiting.

The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility.

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Morten Sejer Hansen

Full Text Available Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min in healthy volunteers.Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min., and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied.For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006.We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers.clinicaltrials.gov NCT02166164.

Effect of Mas-related gene (Mrg) receptors on hyperalgesia in rats with CFA-induced inflammation via direct and indirect mechanisms.

Science.gov (United States)

Jiang, Jianping; Wang, Dongmei; Zhou, Xiaolong; Huo, Yuping; Chen, Tingjun; Hu, Fenjuan; Quirion, Rémi; Hong, Yanguo

2013-11-01

Mas oncogene-related gene (Mrg) receptors are exclusively distributed in small-sized neurons in trigeminal and dorsal root ganglia (DRG). We investigated the effects of MrgC receptor activation on inflammatory hyperalgesia and its mechanisms. A selective MrgC receptor agonist, bovine adrenal medulla peptide 8-22 (BAM8-22) or melanocyte-stimulating hormone (MSH) or the μ-opioid receptor (MOR) antagonist CTAP was administered intrathecally (i.t.) in rats injected with complete Freund's adjuvant (CFA) in one hindpaw. Thermal and mechanical nociceptive responses were assessed. Neurochemicals were measured by immunocytochemistry, Western blot, ELISA and RT-PCR. CFA injection increased mRNA for MrgC receptors in lumbar DRG. BAM8-22 or MSH, given i.t., generated instant short and delayed long-lasting attenuations of CFA-induced thermal hyperalgesia, but not mechanical allodynia. These effects were associated with decreased up-regulation of neuronal NOS (nNOS), CGRP and c-Fos expression in the spinal dorsal horn and/or DRG. However, i.t. administration of CTAP blocked the induction by BAM8-22 of delayed anti-hyperalgesia and inhibition of nNOS and CGRP expression in DRG. BAM8-22 also increased mRNA for MORs and pro-opiomelanocortin, along with β-endorphin content in the lumbar spinal cord and/or DRG. MrgC receptors and nNOS were co-localized in DRG neurons. Activation of MrgC receptors suppressed up-regulation of pronociceptive mediators and consequently inhibited inflammatory pain, because of the activation of up-regulated MrgC receptors and subsequent endogenous activity at MORs. The uniquely distributed MrgC receptors could be a novel target for relieving inflammatory pain. © 2013 The British Pharmacological Society.

Remifentanil analgesia during laser treatment for retinopathy of prematurity: a practical approach in neonatal intensive care unit.

Science.gov (United States)

Demirel, Nihal; Bas, Ahmet Y; Kavurt, Sumru; Celik, Istemi H; Yucel, Husniye; Turkbay, Dursun; Hekimoğlu, Emre; Koc, Orhan

2014-11-01

Retinopathy of prematurity (ROP) is a significant cause of childhood blindness. The aim of this study is to determine the feasibility of remifentanil analgesia during laser treatment of ROP performed in the neonatal intensive care unit (NICU). Remifentanil was infused continuously during the procedure starting with a dose of 0.2 µg/kg/min and increased gradually to 0.6 µg/kg/min to provide an adequate level of analgesia. We enrolled 64 infants. Remifentanil was infused continuously at a mean rate of 0.4 ± 0.1 μg/kg/min. No major adverse effects were observed except in two patients with reversible bradycardia and hypotension. Premature infant pain profile (PIPP) scores revealed no pain. Patients with bronchopulmonary dysplasia had similar remifentanil dosage, intubation duration, and extubation time. Remifentanil analgesia for ROP treatment performed in the NICU by pediatricians is a safe and effective modality. This modality offers a practical solution in hospitals without readily available pediatric anesthetists. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy: comparison of adjuvant propofol and ketamine

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Mefkur Bakan

2014-06-01

Full Text Available OBJECTIVE:Laryngoscopy and stimuli inside the trachea cause an intense sympatho-adrenal response. Remifentanil seems to be the optimal opioid for rigid bronchoscopy due to its potent and short-acting properties. The purpose of this study was to compare bolus propofol and ketamine as an adjuvant to remifentanil-based total intravenous anesthesia for pediatric rigid bronchoscopy.MATERIALS AND METHODS:Forty children under 12 years of age who had been scheduled for a rigid bronchoscopy were included in this study. After midazolam premedication, a 1 µg/kg/min remifentanil infusion was started, and patients were randomly allocated to receive either propofol (Group P or ketamine (Group K as well as mivacurium for muscle relaxation. Anesthesia was maintained with a 1 µg/kg/min remifentanil infusion and bolus doses of propofol or ketamine. After the rigid bronchoscopy, 0.05 µg/kg/min of remifentanil was maintained until extubation. Hemodynamic parameters, emergence characteristics, and adverse events were evaluated.RESULTS:The demographic variables were comparable between the two groups. The decrease in mean arterial pressure from baseline values to the lowest values during rigid bronchoscopy was greater in Group P (p= 0.049, while the reduction in the other parameters and the incidence of adverse events were comparable between the two groups. The need for assisted or controlled mask ventilation after extubation was higher in Group K.CONCLUSION:Remifentanil-based total intravenous anesthesia with propofol or ketamine as an adjuvant drug along with controlled ventilation is a viable technique for pediatric rigid bronchoscopy. Ketamine does not provide a definite advantage over propofol with respect to hemodynamic stability during rigid bronchoscopy, while propofol seems more suitable during the recovery period.

The effect of granisetron dexamethasone combination on postoperative nausea and vomiting in gynecological operations

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Ziya Kaya

2010-06-01

Full Text Available Objectives: Postoperative nausea and vomiting (PONV is one of the most frequent adverse effects of anesthesia. PONV postpones hospital stays and also delays recover and getting better, of the patients. The objective of the current study is to compare efficacy of prophylactic granisetron(40 μ/kg + dexamethasone (4 mg combination against PONV in different anesthesia models.Materials and Methods: 72 patients with an age range of 18-72 years and ASA 1 or 2 were enrolled in the present study. The patients were assigned as group 1 propofol-remifentanil (P-R, group 2 propofol- nitrous oxide (P-N2O, group 3 sevoflurane- nitrous oxide (S-N2O and group 4 sevoflurane-remifentanyl-air (S-R+H. Inductions of the patients in all groups were made with intravenous 2-3 mg/kg propofol, 1μ/kg remifentanil and 0.2 mg/kg cis-atracurium. 4 mg of dexamethasone by bolus and 40 μ/kg of granisetron by infusion were administered to the patients in all groups after induction. During the last 10 minutes of the operation, 1mg/kg tramadol was administered.Postoperative nausea and vomiting, VAS scores, and additional antiemetic needs were recorded during postoperative 48 hours.Results: Postoperative 48 hours follow up revealed that PONV was seen 27%, 16%, 38%, 48% frequencies in (P+R, (P+ N2O, (S+ N2O, (S+R+H groups, respectively.While antiemetic requirement was not observed in (P+ N2O and (S+ N2O groups, the patients in (P+R and (S+R+H groups needed additional antiemetic drugs with a frequency of 5.5% and 11% respectively.Conclusion: Granisetron, dexamethasone combination in different anesthetic models did not reveal significant difference in terms of postoperative nausea, vomiting, and additional antiemetic usage.

An Allometric Model of Remifentanil Pharmacokinetics and Pharmacodynamics

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Eleveld, Douglas J.; Proost, Johannes H.; Vereecke, Hugo; Absalom, Anthony R.; Olofsen, Erik; Vuyk, Jaap; Struys, Michel M. R. F.

Background: Pharmacokinetic and pharmacodynamic models are used to predict and explore drug infusion schemes and their resulting concentration profiles for clinical application. Our aim was to develop a pharmacokinetic-pharmacodynamic model for remifentanil that is accurate in patients with a wide

Intraoperative hyperventilation vs remifentanil during electrocorticography for epilepsy surgery - a case report

DEFF Research Database (Denmark)

Kjaer, Troels W; Madsen, F F; Moltke, F B

2010-01-01

different brain regions in the same patient. METHODS: Hyperventilation and ultra short acting opioid remifentanil were used separately as intraoperative precipitatants of seizure patterns, while recording from subdural and intraventricular electrodes in a patient with temporal lobe epilepsy. Two different...... ictal onset zones appeared in response to hyperventilation and remifentanil. Both zones were resected and the patient has remained essentially seizure free for 1 year. Furthermore, this is the first description of hyperventilation used as an intraoperative seizure precipitant in human focal epilepsy....

Prediction of immediate postoperative pain using the analgesia/nociception index: a prospective observational study.

Science.gov (United States)

Boselli, E; Bouvet, L; Bégou, G; Dabouz, R; Davidson, J; Deloste, J-Y; Rahali, N; Zadam, A; Allaouchiche, B

2014-04-01

The analgesia/nociception index (ANI) is derived from heart rate variability, ranging from 0 (maximal nociception) to 100 (maximal analgesia), to reflect the analgesia/nociception balance during general anaesthesia. This should be correlated with immediate postoperative pain in the post-anaesthesia care unit (PACU). The aim of this study was to evaluate the performance of ANI measured at arousal from general anaesthesia to predict immediate postoperative pain on arrival in PACU. Two hundred patients undergoing ear, nose, and throat or lower limb orthopaedic surgery with general anaesthesia using an inhalational agent and remifentanil were included in this prospective observational study. The ANI was measured immediately before tracheal extubation and pain intensity was assessed within 10 min of arrival in PACU using a 0-10 numerical rating scale (NRS). The relationship between ANI and NRS was assessed using linear regression. A receiver-operating characteristic (ROC) curve was used to evaluate the performance of ANI to predict NRS>3. A negative linear relationship was observed between ANI immediately before extubation and NRS on arrival in PACU. Using a threshold of 3 were both 86% with 92% negative predictive value, corresponding to an area under the ROC curve of 0.89. The measurement of ANI immediately before extubation after inhalation-remifentanil anaesthesia was significantly associated with pain intensity on arrival in PACU. The performance of ANI for the prediction of immediate postoperative pain is good and may assist physicians in optimizing acute pain management. ClinicalTrials.gov NCT01796249.

Extended release local anesthetic agents in a postoperative arthritic pain model.

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Ickowicz, Diana E; Golovanevski, Ludmila; Haze, Amir; Domb, Abraham J; Weiniger, Carolyn F

2014-01-01

Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Antihyperalgesic effects of dexketoprofen and tramadol in a model of postoperative pain in mice - effects on glial cell activation.

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Romero-Alejo, Elizabeth; Puig, Margarita M; Romero, Asunción

2016-08-01

To define likely targets (i.e. glia) and protocols (analgesic combinations) to improve postoperative pain outcomes and reduce chronic pain after surgery. Specifically, to assess the antihyperalgesic effects of the dexketoprofen : tramadol (DEX : TRM) combination, exploring the implication of glial activation. In a mouse model of postincisional pain, we evaluated mechanical nociceptive thresholds (Von Frey) for 21 days postoperatively. We assessed DEX and TRM alone and combined (1 : 1 ratio) on postoperative hyperalgesia (POH, day 1) and delayed latent pain sensitisation (substantiated by a naloxone challenge; PS, day 21). The interactions were analysed using isobolograms, and concomitant changes in spinal glial cell activation were measured. On day 1, DEX completely blocked POH, whereas TRM induced 32% inhibition. TRM, but not DEX, partially (47%) protected against PS, at 21 days. Co-administration of DEX : TRM (1 : 1 ratio) showed additivity for antihyperalgesia. Both drugs and their combination totally inhibited surgery-induced microglia activation on day 1, but had no effect on surgery-induced astrocyte activation (1 day) or re-activation after naloxone (21 days). The DEX : TRM combination could have clinical advantages: a complete prevention of POH after surgery, together with a substantial (48%) inhibition of the development of PS by TRM. Microglia, but not astrocyte activation, could play a relevant role in the development of postoperative pain hypersensitivity. © 2016 Royal Pharmaceutical Society.

Comparison of the effects of two anesthesia maintenance methods by remifentanil or halothane on endoscopic sinus surgery condition

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Seyed mojtaba Karimi

2008-07-01

Full Text Available Introduction: Endoscopic surgery is a new standard method of treatment for chronic sinusitis. During this operation even small amount of bleeding may reduce the visual field of surgeon significantly and make the procedure troublesome. In this study we have compared the operative condition between patients who receive either remifentanil or halothane for general anesthesia. Materials and Methods: Endoscopic sinus surgery was performed in 60 patents. Pre- medication was done by fentanil and midazolam and induction was done by propofol and atracurium. Halothane or remifentanil was used in two groups of patients respectively for anesthesia maintenance. Monitoring was performed during anesthesia. Bleeding volume was measured and operation field condition was assessed by the surgeon. Results: Personal characteristics such as age and sex were the same in both groups. Intra- operative systolic blood pressures was significantly lower in remifentanil group but diastolic and mean blood pressure and heart rate didn’t change after induction and during maintenance in both groups. Recovery time in remifentanil group was also significantly shorter than halothane group. Finally bleeding volume was lower and operation field condition was better significantly in remifentanil group. Conclusion: Remifentanil is a good choice to maintain an ideal anesthesia for endoscopic sinus surgery.    

The effects of an intraperitoneal single low dose of ketamine in attenuating the postoperative skin/muscle incision and retraction-induced pain related to the inhibition of N-methyl-D-aspartate receptors in the spinal cord.

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Shen, Yu; Xu, Li; Liu, Ming; Lei, Yishan; Gu, Xiaoping; Ma, Zhengliang

2016-03-11

Chronic postoperative pain (CPOP) is a common clinical problem which might be related to central sensitization. It has been widely accepted that NMDA (N-methyl-D-aspartate) receptors are among the triggers of central sensitization. Ketamine is a non-competitive NMDA receptor antagonist that is widely used in alleviating postoperative pain, but its effect on CPOP has been rarely reported. In the present study, the skin/muscle incision and retraction (SMIR) model was used to investigate the role of NMDARs in chronic postoperative pain and the effect of an intraperitoneal single low dose ketamine (10mg/kg) of attenuating SMIR-induced CPOP. We assessed pain behaviours after a SMIR operation by paw withdrawal threshold (PWMT) and paw withdrawal latency (PWMTL). Western blotting were performed to examine the role of NMDARs in SMIR-induced CPOP and the effect of ketamine on the expression and phosphorylation of NMDARs. The SMIR operation induced long-lasting mechanical hyperalgesia, and the up-regulation of phosphorylated NMDARs and total NMDARs at the spinal level. A single intraperitoneal administration of low dose ketamine (10mg/kg) during surgery alleviated pain behaviors and inhibited the up-regulation of phosphorylated NMDARs and total NMDARs. Our datas suggested that NMDARs play important roles in SMIR-induced CPOP. A single intraperitoneal low dose of ketamine could attenuate SMIR-induced CPOP, which might be associated with the inhibition of NMDARs. Our finding might provide a new, simple method of addressing CPOP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of pectoral nerve block on postoperative pain and quality of recovery in patients undergoing breast cancer surgery: A randomised controlled trial.

Science.gov (United States)

Kamiya, Yoshinori; Hasegawa, Miki; Yoshida, Takayuki; Takamatsu, Misako; Koyama, Yu

2018-03-01

In recent years, thoracic wall nerve blocks, such as the pectoral nerve (PECS) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery. The effect of PECS block on quality of recovery (QoR) after breast cancer surgery has not been evaluated. To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery. Randomised controlled study. A tertiary hospital. Sixty women undergoing breast cancer surgery between April 2014 and February 2015. The patients were randomised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25% after induction of anaesthesia (PECS group) or a saline mock block (control group). The patients answered a 40-item QoR questionnaire (QoR-40) before and 1 day after breast cancer surgery. Numeric Rating Scale score for postoperative pain, requirement for intra-operative propofol and remifentanil, and QoR-40 score on postoperative day 1. PECS block combined with propofol-remifentanil anaesthesia significantly improved the median [interquartile range] pain score at 6 h postoperatively (PECS group 1 [0 to 2] vs. Control group 1 [0.25 to 2.75]; P = 0.018]. PECS block also reduced propofol mean (± SD) estimated target blood concentration to maintain bispectral index (BIS) between 40 and 50 (PECS group 2.65 (± 0.52) vs. Control group 3.08 (± 0.41) μg ml; P PECS group 10.5 (± 4.28) vs. Control group 10.4 (± 4.68) μg kg h; P = 0.95). PECS block did not improve the QoR-40 score on postoperative day 1 (PECS group 182 [176 to 189] vs. Control group 174.5 [157.75 to 175]). In patients undergoing breast cancer surgery, PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil, due to the inability of the PECS block to reach the internal mammary area. Further, PECS

Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

DEFF Research Database (Denmark)

Pedersen, J L; Rung, G W; Kehlet, H

1997-01-01

BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....... The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds...... between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. CONCLUSION: Sympathetic nerve block did not change...

Demarcation of secondary hyperalgesia zones

DEFF Research Database (Denmark)

Ringsted, Thomas K; Enghuus, Casper; Petersen, Morten A

2015-01-01

of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). NEW METHOD: The study was a two.......0001). No day-to-day or observer-to-observer differences in SHAs were observed. Intraclass correlation coefficients, in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability between observers. COMPARISON WITH EXISTING METHODS: No standardized approach in SHA-assessment has hitherto been...... presented. CONCLUSIONS: This is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used....

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

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Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

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Masocha Willias

2010-12-01

Full Text Available Abstract Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p. to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg had no significant activity, minocycline (25 to 100 mg/kg produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg and a selective COX-2 inhibitor, CAY10404 (10 mg/kg had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg or minocycline (50 mg/kg did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH limb paw pressure ratios and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg or

Remifentanil kan i særlige tilfælde anvendes som alternativ til epiduralanalgesi til fødende

DEFF Research Database (Denmark)

Ravn, Toke; Afshari, Arash

2011-01-01

Epidural analgesia remains the gold standard during labour, but is contraindicated in several clinical settings due to increased risk of serious complications. There are few effective alternatives to epidural analgesia. However, there is an increasing interest for the use of remifentanil...... as a labour analgesic. In this focused review, we describe the effect, dose and safety of remifentanil for the mother and fetus/neonate. Remifentanil appears to have a potential as labour analgesic. Careful monitoring of the parturient and the newborn is advised....

Remifentanil at induction of general anesthesia for cesarean section: Double blind,randomized clinical trial

OpenAIRE

Behdad, Shekoufeh; Ayatollahi, Vida; Harrazi, Hamid; Nazemian, Naderali; Heiranizadeh, Najmeh; Baghianimoghadam, Behnam

2013-01-01

Introduction: Remifentanil, with its rapid activity onset and short duration of action, may be more effective than other opioids for providing hemodynamic stability during obstetric anesthesia. However, there is some evidence of adverse effects on neonatal respiratory function. We investigated maternal and fetal effects of Remifentanil during cesarean section surgery. Methods: Eighteen women with singleton term pregnancies, and physical class status of I or II as defined by the American Socie...

Andrographolide Inhibits Mechanical and Thermal Hyperalgesia in a Rat Model of HIV-Induced Neuropathic Pain

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Zhihua Yi

2018-06-01

Full Text Available Aim: In this study, we investigated whether andrographolide (Andro can alleviate neuropathic pain induced by HIV gp120 plus ddC treatment and the mechanism of its action.Methods: The paw withdrawal threshold and the paw withdrawal latency were observed to assess pain behaviors in all groups of the rats, including control group, control combined with Andro treatment group, sham group, gp120 combined with ddC treatment group, gp120 plus ddC combined with A438079 treatment group, and gp120 plus ddC combined with Andro treatment by intrathecally injecting at a dose of 25 μg/20 μl group. The protein expression levels of the P2X7 receptor, tumor necrosis factor-α-receptor (TNFα-R, interleukin-1β (IL-1β, IL-10, phospho-extracellular regulated protein kinases (ERK (p-ERK in the L4–L6 dorsal root ganglia (DRG were measured by western blotting. Real-time quantitative polymerase chain reaction was used to test the mRNA expression level of the P2X7 receptor. Double-labeling immunofluorescence was used to identify the co-localization of the P2X7 receptor with glial fibrillary acidic protein (GFAP in DRG. Molecular docking was performed to identify whether the Andro interacted perfectly with the rat P2X7 (rP2X7 receptor.Results: Andro attenuated the mechanical and thermal hyperalgesia in gp120+ddC-treated rats and down-regulated the P2X7 receptor mRNA and protein expression in the L4–L6 DRGs of gp120+ddC-treated rats. Additionally, Andro simultaneously decreased the expression of TNFα-R and IL-1β protein, increased the expression of IL-10 protein in L4–L6 DRGs, and inhibited the activation of ERK signaling pathways. Moreover, Andro decreased the co-expression of GFAP and the P2X7 receptor in the SGCs of L4–L6 DRG on 14th day after surgery.Conclusion: Andro decreased the hyperalgesia induced by gp120 plus ddC.

Pharmacological interaction between oxcarbazepine and two COX inhibitors in a rat model of inflammatory hyperalgesia.

Science.gov (United States)

Stepanović-Petrović, Radica M; Tomić, Maja A; Vučković, Sonja M; Poznanović, Goran; Ugrešić, Nenad D; Prostran, Milica Š; Bošković, Bogdan

2011-01-01

Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The combination of different drugs activates both central and peripheral pain inhibitory pathways to induce additive or synergistic antinociception, and this interaction may allow lower doses of each drug combined and improve the safety profile, with lower side-effects. This study aimed to examine the effects of oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model of inflammatory hyperalgesia, and determine the type of interaction between drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in a fixed-dose fractions of the ED₅₀ and the type of interaction was determined by isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120 mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose-dependent anti-hyperalgesia in carrageenan-injected rats. ED₅₀ values (mean±SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17±3.65, 47.07±10.27 and 13.05±1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations induced significant and dose-dependent anti-hyperalgesia. Isobolographic analysis revealed that oxcarbazepine exerts a synergistic interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs in combination. In contrast, there was an additive interaction with etodolac. Synergistic interaction of oxcarbazepine with ibuprofen and its additive interaction with etodolac provide new information about the combination pain treatment and could be explored further in patients with inflammatory pain. Adverse effect analysis of the combinations is necessary to verify possible clinical use of the mixtures. Copyright �

Analysis of Memory Formation during General Anesthesia (Propofol/Remifentanil) for Elective Surgery Using the Process-dissociation Procedure.

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Hadzidiakos, Daniel; Horn, Nadja; Degener, Roland; Buchner, Axel; Rehberg, Benno

2009-08-01

There have been reports of memory formation during general anesthesia. The process-dissociation procedure has been used to determine if these are controlled (explicit/conscious) or automatic (implicit/unconscious) memories. This study used the process-dissociation procedure with the original measurement model and one which corrected for guessing to determine if more accurate results were obtained in this setting. A total of 160 patients scheduled for elective surgery were enrolled. Memory for words presented during propofol and remifentanil general anesthesia was tested postoperatively by using a word-stem completion task in a process-dissociation procedure. To assign possible memory effects to different levels of anesthetic depth, the authors measured depth of anesthesia using the BIS XP monitor (Aspect Medical Systems, Norwood, MA). Word-stem completion performance showed no evidence of memory for intraoperatively presented words. Nevertheless, an evaluation of these data using the original measurement model for process-dissociation data suggested an evidence of controlled (C = 0.05; 95% confidence interval [CI] 0.02-0.08) and automatic (A = 0.11; 95% CI 0.09-0.12) memory processes (P memory processes was obtained. The authors report and discuss parallel findings for published data sets that were generated by using the process-dissociation procedure. Patients had no memories for auditory information presented during propofol/remifentanil anesthesia after midazolam premedication. The use of the process-dissociation procedure with the original measurement model erroneously detected memories, whereas the extended model, corrected for guessing, correctly revealed no memory.

Differences in maternal temperature during labour with remifentanil patient-controlled analgesia or epidural analgesia: a randomised controlled trial

NARCIS (Netherlands)

Douma, M.R.; Stienstra, R.; Middeldorp, J.M.; Arbous, M.S.; Dahan, A

2015-01-01

BACKGROUND: Epidural analgesia and remifentanil patient-controlled analgesia are two popular techniques for the treatment of labour pain, each with its own efficacy and toxicity. METHODS: Parturients requesting analgesia were randomly assigned to either patient-controlled intravenous remifentanil or

Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial

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Freeman Liv M

2012-07-01

Full Text Available Abstract Background Pain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments. Methods/design The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia. Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief. Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity, mode of delivery and maternal and neonatal side effects. The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared. Discussion This study, considering cost

Comparison between local anaesthesia with remifentanil and total intravenous anaesthesia for operative hysteroscopic procedures in day surgery

DEFF Research Database (Denmark)

Majholm, B; Bartholdy, J; Clausen, H V

2012-01-01

BACKGROUND: /st>This study aimed at comparing total i.v. anaesthesia (TIVA) with monitored anaesthesia care (MAC) during day-surgery operative hysteroscopy regarding: operation time, time to mobilization and discharge, and patient satisfaction. METHODS: /st>Ninety-one healthy women were randomized...... to MAC with paracervical local anaesthesia and remifentanil or to TIVA with propofol and remifentanil. Time from arrival to leaving the operating theatre, time from arrival in the recovery room to mobilization and discharge readiness, and patient satisfaction with MAC and TIVA were observed. RESULTS: /st.......003). CONCLUSIONS: /st>Paracervical local anaesthesia combined with remifentanil is suitable for operative hysteroscopy in day surgery....

Depth of anaesthesia monitoring in obese patients: a randomized study of propofol-remifentanil

DEFF Research Database (Denmark)

Meyhoff, C S; Henneberg, S W; Jørgensen, B G

2009-01-01

BACKGROUND: In obese patients, depth of anaesthesia monitoring could be useful in titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia monitoring would reduce recovery time and use of anaesthetics in obese patients receiving propofol and remifentanil. METHODS: We investig......BACKGROUND: In obese patients, depth of anaesthesia monitoring could be useful in titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia monitoring would reduce recovery time and use of anaesthetics in obese patients receiving propofol and remifentanil. METHODS: We...... investigated 38 patients with a body mass index >or=30 kg/m(2) scheduled for an abdominal hysterectomy. Patients were randomized to either titration of propofol and remifentanil according to a cerebral state monitor (CSM group) or according to usual clinical criteria (control group). The primary end point.......04). During surgery, when the cerebral state index was continuously between 40 and 60, the corresponding optimal propofol infusion rate was 10 mg/kg/h based on ideal body weight. CONCLUSION: No significant reduction in time to eye opening could be demonstrated when a CSM was used to titrate propofol...

Efficacy and side effects of intravenous remifentanil patient-controlled analgesia used in a stepwise approach for labour: an observational study.

Science.gov (United States)

Tveit, T O; Halvorsen, A; Seiler, S; Rosland, J H

2013-01-01

Remifentanil has a suitable pharmacological profile for labour analgesia. In this prospective, observational study, intravenous patient-controlled analgesia with remifentanil, using stepwise bolus doses without background infusion, was examined during the first and second stages of labour. Outcomes were pain reduction, maternal satisfaction, maternal and neonatal side effects and remifentanil metabolism in the neonate. Parturients with normal term singleton pregnancies were recruited. The initial remifentanil bolus dose was 0.15 μg/kg, increasing in steps of 0.15 μg/kg, with a 2-min lock-out. Pain scores using a 100 mm visual analogue scale, systolic and diastolic blood pressures, respiratory rate and maternal sedation were recorded every 15 min. Maternal oxygen saturation and heart rate were monitored continuously. Neonatal data included Apgar scores, clinical examination, naloxone use, resuscitation, umbilical cord blood gases and remifentanil concentrations. Forty-one parturients were enrolled. Pain scores were significantly reduced in the first 3 h of patient-controlled analgesia use compared to baseline, and at the end of the first and second stages of labour (Panalgesia. The mean highest dose of remifentanil was 0.7 μg/kg [range 0.3-1.05]. Ninety-three percent of patients were satisfied with their analgesia. The lowest oxygen saturation was 91% and the lowest respiratory rate was 9 breaths/min. Eleven parturients (27%) received supplemental oxygen due to oxygen saturations neonatal data reassuring. Remifentanil intravenous patient-controlled analgesia provides adequate pain relief and high maternal satisfaction during the first and second stages of labour. Maternal sedation and respiratory depression may occur, but no serious neonatal side effects were recorded. Careful monitoring is mandatory. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Survey of Intravenous Remifentanil Use for Labor Analgesia at Academic Medical Centers in the United States.

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Aaronson, Jaime; Abramovitz, Sharon; Smiley, Richard; Tangel, Virginia; Landau, Ruth

2017-04-01

Remifentanil is most commonly offered when neuraxial labor analgesia is contraindicated. There is no consensus regarding the optimal administration, dosing strategy, or requirements for maternal monitoring, which may pose a patient safety issue. This exploratory survey evaluated the current practices regarding remifentanil use for labor analgesia at academic centers in the United States. Of 126 obstetric anesthesia directors surveyed, 84 (67%) responded. In 2014 to 2015, an estimated 36% (95% confidence interval: 25.7-46.3) of centers used remifentanil, most of which did so less than 5 times. Some serious maternal and neonatal respiratory complications occurred, emphasizing that clinical protocols and adequate monitoring are key to ensure maternal and neonatal safety.

Time course of primary and secondary hyperalgesia after heat injury to the skin

DEFF Research Database (Denmark)

Møiniche, S; Dahl, J B; Kehlet, H

1993-01-01

the injury in any volunteer. These findings suggest post-injury development of secondary hyperalgesia to be a dynamic process, closely related in time to a peripheral nociceptive input, with reversal to normal when the peripheral lesion disappears. These observations may be relevant to the concept of "pre......We have examined the time course of, and relationship between, primary and secondary hyperalgesia after thermal injury to the skin in humans. Burn injuries (15 x 25 mm rectangular thermode, 49 degrees C, 5 min) were produced in eight healthy, unmedicated male volunteers, on the medial side...... of the right calf, on two occasions at least 8 days apart. Heat pain detection thresholds (HPDT), heat pain tolerance (HPT), mechanical pain detection threshold (MPDT) and the intensity of burn-injury induced erythema (skin erythema index, SEI) were assessed inside the burn injury. HPT was assessed only in one...

Repeated forced swim stress enhances CFA-evoked thermal hyperalgesia and affects the expressions of pCREB and c-Fos in the insular cortex.

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Imbe, H; Kimura, A; Donishi, T; Kaneoke, Y

2014-02-14

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. The insular (IC) and anterior cingulate cortices (ACC) are the regions exhibiting most reliable pain-related activity. And the IC and ACC play an important role in pain modulation via the descending pain modulatory system. In the present study we examined the expression of phospho-cAMP response element-binding protein (pCREB) and c-Fos in the IC and ACC after forced swim stress (FS) and complete Freund's adjuvant (CFA) injection to clarify changes in the cerebral cortices that affect the activity of the descending pain modulatory system in the rats with stress-induced hyperalgesia. FS (day 1, 10min; days 2-3, 20min) induced an increase in the expression of pCREB and c-Fos in the anterior IC (AIC). CFA injection into the hindpaw after the FS shows significantly enhanced thermal hyperalgesia and induced a decrease in the expression of c-Fos in the AIC and the posterior IC (PIC). Quantitative image analysis showed that the numbers of c-Fos-immunoreactive neurons in the left AIC and PIC were significantly lower in the FS+CFA group (L AIC, 95.9±6.8; L PIC, 181.9±23.1) than those in the naive group (L AIC, 151.1±19.3, pCFA-induced thermal hyperalgesia through dysfunction of the descending pain modulatory system. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Remifentanil in a patient with Huntington's chorea - case report ...

African Journals Online (AJOL)

Relatively few published case reports related to the anaesthetic management of Huntington's chorea (HC) exist. At the time of surgery no publications were found related to remifentanil's use in patients with HC. This case report describes the management of a confirmed HC patient requiring urgent decompression of a spinal ...

Is heat pain detection threshold associated with the area of secondary hyperalgesia following brief thermal sensitization? A study of healthy volunteers - design and detailed plan of analysis.

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Hansen, Morten Sejer; Wetterslev, Jørn; Pipper, Christian Bressen; Asghar, Mohammad Sohail; Dahl, Jørgen Berg

2016-05-31

Several factors are believed to influence the development and experience of pain. Human clinical pain models are central tools, in the investigation of basic physiologic pain responses, and can be applied in patients as well as in healthy volunteers. Each clinical pain model investigates different aspects of the human pain response. Brief thermal sensitization induces a mild burn injury, resulting in development of primary hyperalgesia at the site of stimulation, and secondary hyperalgesia surrounding the site of stimulation. Central sensitization is believed to play an important role in the development of secondary hyperalgesia; however, a possible association of secondary hyperalgesia following brief thermal sensitization and other heat pain models remains unknown. Our aim with this study is to investigate how close the heat pain detection threshold is associated with the size of the area of secondary hyperalgesia induced by the clinical heat pain model: Brief thermal sensitization. We aim to include 120 healthy participants. The participants will be tested on two separate study days with the following procedures: i) Brief thermal sensitization, ii) heat pain detection threshold and iii) pain during thermal stimulation. Additionally, the participants will be tested with the Pain Catastrophizing Scale and Hospital Anxiety and Depression Scale questionnaires. We conducted statistical simulations based on data from our previous study, to estimate an empirical power of 99.9 % with α of 0.05. We define that an R(2) heat stimulation, and thus may be a biomarker of an individual's pain sensitivity. The number of studies investigating secondary hyperalgesia is growing; however basic knowledge of the physiologic aspects of secondary hyperalgesia in humans is still incomplete. We therefore find it interesting to investigate if HPDT, a known quantitative sensory test, is associated with areas of secondary hyperalgesia following brief thermal sensitization Clinicaltrials

Postoperative recovery profile after elective abdominal hysterectomy: a prospective, observational study of a multimodal anaesthetic regime

DEFF Research Database (Denmark)

Jensen, Kenneth; Kehlet, Henrik; Lund, Claus M

2009-01-01

insufficiency and time of discharge readiness. RESULTS: The structured regime consisting of total intravenous anaesthesia (propofol-remifentanil), well defined fluid administration, prophylactic antiemetics (dexamethasone, ondansetron, droperidol), weak analgesics (celecoxib, paracetamol) and intraoperative......BACKGROUND AND OBJECTIVE: To evaluate the applicability, effectiveness, immediate postoperative complaints and requirements for a postanaesthesia care unit stay after elective abdominal hysterectomy under a well defined, multimodal anaesthetic regime. METHODS: Observational study of 145 consecutive......, was seen in 52%. CONCLUSION: We conclude that a structured multimodal anaesthetic regime is feasible in daily clinical practice and advantageous, and that postoperative pain and oxygen requirements (to sustain an SpO2 >92%) are the major determinants for length of stay in the postanaesthesia care unit...

Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.

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Marco Sisignano

Full Text Available Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs. However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.

Propofol-remifentanil or sevoflurane for children undergoing magnetic resonance imaging?

DEFF Research Database (Denmark)

Pedersen, N A; Jensen, Anne Gert; Kilmose, L

2013-01-01

Magnetic resonance imaging (MRI) of children is generally performed under sedation or with general anaesthesia (GA), but the ideal regimen has not been found. The aim of this study was to see if propofol-remifentanil would be a suitable alternative for the maintenance of anaesthesia...

The effects of secondhand smoke on postoperative pain and fentanyl consumption.

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Aydogan, Mustafa Said; Ozturk, Erdogan; Erdogan, Mehmet Ali; Yucel, Aytac; Durmus, Mahmut; Ersoy, Mehmet Ozcan; Colak, Cemil

2013-08-01

Although the need for increased postoperative analgesia in smokers has been described, the effect of secondhand smoke on postoperative analgesia requirements has not been studied. We examined the effects of secondhand smoke on fentanyl consumption and postoperative pain. In this study, 101 patients (American Society of Anesthesiology physical status I and II) who underwent abdominal hysterectomy were divided into 3 groups according to history of exposure to cigarette smoke as per medical records which was retrospectively confirmed by measurement of serum cotinine: smokers (n = 28), nonsmokers (n = 31), and secondhand smokers (n = 32). All patients received propofol-remifentanil total intravenous anesthesia and used fentanyl patient controlled analgesia for postoperative pain. The fentanyl consumption visual analogue scale-pain intensity (VAS-PI) score and side effects were recorded in the postanesthesia care unit (PACU) and at 2, 4, 6, and 24 h after surgery. Fentanyl consumption at all the evaluation time points was significantly higher in secondhand smokers than in nonsmokers (P secondhand smokers was lower than that in smokers in the PACU and at 24 h (P secondhand smokers than in nonsmokers (P effects such as nausea, vomiting, and dizziness (P > 0.05). Secondhand smoking was associated with increased postoperative fentanyl consumption, and increased VAS-PI scores. These findings may be beneficial for managing postoperative pain in secondhand smokers.

Dose of rocuronium for rapid tracheal intubation following remifentanil 2 μg kg-1 and propofol 2 mg kg-1.

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Oh, Ah-Young; Cho, Suk-Ju; Seo, Kwang-Suk; Ryu, Jung-Hee; Han, Sung-Hee; Hwang, Jung-Won

2013-09-01

Full relaxation is not mandatory for successful tracheal intubation. We tried to find the dose of rocuronium that gave acceptable intubation conditions in a rapid sequence intubation with remifentanil and propofol. A dose-finding study of rocuronium using a modified Dixon's up-and-down method. A single tertiary care teaching hospital. Patients undergoing elective surgery under general anaesthesia. After premedication with midazolam and glycopyrrolate, anaesthesia was induced using remifentanil 2 μg kg and propofol 2 mg kg, and a predetermined dose of rocuronium was administered. The dose of rocuronium was determined by a modified Dixon's up-and-down method starting from 0.8 mg kg with an interval of 0.1 or 0.05 mg kg. Intubation was performed 60 s after the start of the rocuronium injection. Intubation conditions were graded as excellent, good or poor. Excellent or good were regarded as clinically acceptable. A dose of rocuronium needed for acceptable intubation condition in 50% of patients (ED50) during rapid tracheal intubation after induction of anaesthesia with remifentanil and propofol. Twenty-eight patients were enrolled to obtain six crossovers. The ED50 of rocuronium was 0.20 mg kg (95% confidence interval, CI 0.17 to 0.23 mg kg) by a modified Dixon's up-and-down method. After induction of anaesthesia with remifentanil 2 μg kg and propofol 2 mg kg, the ED50 of rocuronium for acceptable intubation condition was 0.20 mg kg (95% CI, 0.17 to 0.23 mg kg) for rapid sequence intubation. Thus, we recommend that the intubation dose should be 0.8 mg kg. Clinical trial registration KCT0000094.

The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical hyperalgesia in patients with neuromyelitis optica.

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Hannah L Pellkofer

Full Text Available Recurrent myelitis is one of the predominant characteristics in patients with neuromyelitis optica (NMO. While paresis, visual loss, sensory deficits, and bladder dysfunction are well known symptoms in NMO patients, pain has been recognized only recently as another key symptom of the disease. Although spinal cord inflammation is a defining aspect of neuromyelitis, there is an almost complete lack of data on altered somatosensory function, including pain. Therefore, eleven consecutive patients with NMO were investigated regarding the presence and clinical characteristics of pain. All patients were examined clinically as well as by Quantitative Sensory Testing (QST following the protocol of the German Research Network on Neuropathic Pain (DFNS. Additionally, plasma endocannabinoid levels and signs of chronic stress and depression were determined. Almost all patients (10/11 suffered from NMO-associated neuropathic pain for the last three months, and 8 out of 11 patients indicated relevant pain at the time of examination. Symptoms of neuropathic pain were reported in the vast majority of patients with NMO. Psychological testing revealed signs of marked depression. Compared to age and gender-matched healthy controls, QST revealed pronounced mechanical and thermal sensory loss, strongly correlated to ongoing pain suggesting the presence of deafferentation-induced neuropathic pain. Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat hyperalgesia was highly correlated to the time since last relapse of NMO. Patients with NMO exhibited significant mechanical and thermal dysesthesia, namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover, they presented frequently with either abnormal mechanical hypoalgesia or hyperalgesia, which depended significantly on plasma levels of the endogenous cannabinoid 2-arachidonoylglycerole (2-AG. These data emphasize the high prevalence of neuropathic pain and hyperalgesia

Adenosine for postoperative analgesia: A systematic review and meta-analysis.

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Xin Jin

Full Text Available Perioperative infusion of adenosine has been suggested to reduce the requirement for inhalation anesthetics, without causing serious adverse effects in humans. We conducted a meta-analysis of randomized controlled trials evaluating the effect of adenosine on postoperative analgesia.We retrieved articles in computerized searches of Scopus, Web of Science, PubMed, EMBASE, and Cochrane Library databases, up to July 2016. We used adenosine, postoperative analgesia, and postoperative pain(s as key words, with humans, RCT, and CCT as filters. Data of eligible studies were extracted, which included pain scores, cumulative opioid consumption, adverse reactions, and vital signs. Overall incidence rates, relative risk (RR, and 95% confidence intervals (CI were calculated employing fixed-effects or random-effects models, depending on the heterogeneity of the included trials.In total, 757 patients from 9 studies were included. The overall effect of adenosine on postoperative VAS/VRS scores and postoperative opioid consumption was not significantly different from that of controls (P >0.1. The occurrence of PONV and pruritus was not statistically significantly different between an adenosine and nonremifentanil subgroup (P >0.1, but the rate of PONV occurrence was greater in the remifentanil subgroup (P 0.1.Adenosine has no analgesic effect or prophylactic effect against PONV, but reduce systolic blood pressure and heart rates. Adenosine may benefit patients with hypertension, ischemic heart disease, and tachyarrhythmia, thereby improving cardiac function.

Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

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Zhiyong Wang

2017-01-01

Full Text Available Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP, a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI. The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

Effect of riluzole on acute pain and hyperalgesia in humans

DEFF Research Database (Denmark)

Hammer, N A; Lillesø, J; Pedersen, J L

1999-01-01

Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. Therefore, we have examined the acute analgesic effect of riluzole in a human model of inflammatory pain induced by a thermal...... injury on the distal leg (47 degrees C, 7 min, 12.5 cm2) in 20 healthy volunteers. Hyperalgesia to mechanical and heat stimuli were examined by von Frey hairs and thermodes. We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days...

Incidence of persistent postoperative pain after hepatectomies with 2 regimes of perioperative analgesia containing ketamine.

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Masgoret, Paula; Gomar, Carmen; Tena, Beatriz; Taurá, Pilar; Ríos, José; Coca, Miquel

2017-04-01

Studies designed to assess persistent postoperative pain (PPP) incidence after hepatectomies are lacking. Our aim was to assess PPP incidence 6 months after hepatectomies with intravenous (IV) or epidural (EPI) analgesia containing ketamine.Prospective observational comparative study between 2 cohorts of patients submitted to hepatectomy. Patients received 1 of 2 analgesic regimes containing ketamine: EPI group or IV group. Visual analog scale (VAS), Neuropathic Pain Symptom Inventory (NPSI), Pain Catastrophizing Scale (PCS), and quantitative sensorial testing (QST: to determine area of hyperalgesia/allodynia) were assessed preoperatively and postoperatively at 2 h, 24 h, 7 days, 1 month, and 6 months. VAS ≥ 1 at 1 and 6 months was considered indicative of PPP and VAS > 3 was considered as not controlled pain. Side effects and complications were registered.Forty-four patients were included: 23 in EPI group and 21 in IV group. Patients in IV group were older and had more comorbidities. No patient presented VAS > 3 at 1 or 6 months. VAS ≥ 1 at 1 and 6 months was 36.4% and 22.7%, respectively. No differences in VAS, NPSI, or PCS were found between groups. Allodynia/hyperalgesia area did not differ between groups and was infrequent and slight. Pain pressure threshold in the wound vertical component was significantly higher in EPI group after 7 days. IV group showed more cognitive side effects.Incidence of PPP at 6 months after open hepatectomies with EPI or IV analgesia containing ketamine was lower than previously reported for other abdominal surgeries.Ketamine influence on low PPP incidence and hyperalgesia cannot be discarded.

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles

Science.gov (United States)

Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-01-01

Abstract Background: Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Methods: Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Results: Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events. PMID:27930531

Generalized deep-tissue hyperalgesia in patients with chronic low-back pain

DEFF Research Database (Denmark)

O'Neill, Søren; Manniche, Claus; Graven-Nielsen, Thomas

2007-01-01

be demonstrated in a group of patients with chronic low-back pain with intervertebral disc herniation. Twelve patients with MRI confirmed lumbar intervertebral disc herniation and 12 age and sex matched controls were included. Subjects were exposed to quantitative nociceptive stimuli to the infraspinatus...... in the anterior tibialis muscle compared to controls. In conclusion, generalized deep-tissue hyperalgesia was demonstrated in chronic low-back pain patients with radiating pain and MRI confirmed intervertebral disc herniation, suggesting that this central sensitization should also be addressed in the pain......Some chronic painful conditions including e.g. fibromyalgia, whiplash associated disorders, endometriosis, and irritable bowel syndrome are associated with generalized musculoskeletal hyperalgesia. The aim of the present study was to determine whether generalized deep-tissue hyperalgesia could...

GABAergic mechanisms are involved in the antihyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory hyperalgesia.

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Stepanović-Petrović, Radica M; Tomić, Maja A; Vucković, Sonja M; Kocev, Nikola; Ugresić, Nenad D; Prostran, Milica S; Bosković, Bogdan

2008-01-01

The purpose of this study was to investigate the involvement of GABAergic mechanisms in the antihyperalgesic effect of carbamazepine and oxcarbazepine by examining the effect of bicuculline (GABA(A) receptor antagonist) on these effects of antiepileptic drugs. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: (1) the development of hyperalgesia induced by Con A; (2) the effects of carbamazepine/oxcarbazepine on Con A-induced hyperalgesia, and (3) the effects of bicuculline on the carbamazepine/oxcarbazepine antihyperalgesia. Intraperitoneally injected bicuculline (0.5-1 mg/kg, i.p.) exhibited significant suppression of the systemic antihyperalgesic effects of carbamazepine (27 mg/kg, i.p.) and oxcarbazepine (80 mg/kg, i.p.). When applied intraplantarly, bicuculline (0.14 mg/paw, i.pl.) did not produce any change in the peripheral antihyperalgesic effects of carbamazepine (0.14 mg/paw, i.pl.) and oxcarbazepine (0.5 mg/paw, i.pl.). Bicuculline alone did not produce an intrinsic effect in the paw-pressure test. These results indicate that the antihyperalgesic effects of carbamazepine and oxcarbazepine against inflammatory hyperalgesia involve in part the GABAergic inhibitory modulation of pain transmission at central, but not at peripheral sites, which is mediated via GABA(A) receptor activation. Copyright 2008 S. Karger AG, Basel.

Comparative evaluation of the cerebral state index/sup TM/ and bispectral index/sup TM/ monitoring during propofol-remifentanil anesthesia for open heart surgery

International Nuclear Information System (INIS)

Shahbazi, S.; Saem, J.

2007-01-01

The Cerebral State index (CSI) is a new index based on electroencephalogram to monitor depth of anesthesia. Transferring guidelines for titration of the Bispectral index (BIS) to the CSI depends on their compatibility. We compared the relationship between BIS and CSI values during propofol-remifentanil anesthesia. Forty one adult patients about to have open heart surgeries were enrolled. The skin was prepped and electrodes of both monitors were applied according to the manufacturers recommendations. The anesthesia was induced by midazolam, propofol, remifentanil and pancuronium and maintained by propofol and remifentanil and 50% nitrous oxide in oxygen. The BIS and CSI values were recorded in 37 pre-determined milestones during the operation and the anesthetic drugs were adjusted according to clinical signs of light anesthesia regardless of the CSI or BIS values. The BIS and CSI values decreased progressively from pre induction values of 93.15 (55-100) and 88.86 (52-100) to post induction values of 38.72 (16-71) and 40.27 (5-69), respectively. These values showed good linear correlation during laryngoscopy, before and after surgical incision and during CPB; R=0.695 with determination coefficient of 0.483. We found a good correlation between BIS and CSI values. Our results might serve as a blue print for a rational translation of BIS into CSI values. (author)

Does naloxone reinstate secondary hyperalgesia in humans after resolution of a burn injury?

DEFF Research Database (Denmark)

Pereira, Manuel P; Werner, Mads U; Ringsted, Thomas K

2013-01-01

Development of secondary hyperalgesia following a cutaneous injury is a centrally mediated, robust phenomenon. The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear. Recent animal studies, carried out after the resolution of inflammatory pain...

Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency

DEFF Research Database (Denmark)

Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna

2017-01-01

Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would...... to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids......, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean...

The influence of various anesthesia techniques on postoperative recovery and discharge criteria among geriatric patients

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Dilsen Ornek

2010-01-01

Full Text Available OBJECTIVE: We aim to compare selective spinal anesthesia and general anesthesia with regard to postoperative recovery and fast-track eligibility in day surgeries. MATERIALS AND METHOD: Sixty geriatric outpatient cases, with ASA II-III physical status and requiring shortduration transurethral intervention, were enrolled in the study. The cases were split into 2 groups: as general anesthesia (Group GA and selective spinal anesthesia (Group SSA. Group GA (n = 30 received propofol 2 mg kg-1 (until loss of eyelash reflex, remifentanil induction 0.5-1 µg kg-1, and laryngeal mask. Maintenance was achieved by 4-6% desflurane in 60% N2O and 40% O2 along with remifentanil infusion at 0.05 µg /kg-1 /min-1. Drugs were discontinued after the withdrawal of the ureteroscope, and extubation was carried out with 100% O2. Group SSA (n = 30 received 0.5% spinal anesthesia via L4-5 space by 0.5% hyperbaric bupivacaine 5 mg. Anesthesia preparation time, time to surgical anesthesia level, postoperative fast-tracking, and time to White-Song recovery score of 12, were noted. In the operating room, we evaluated hemodynamics, nausea/vomiting, surgeon and patient satisfaction with anesthesia, perioperative midazolam-fentanyl administration, postoperative pain, and discharge time. RESULTS: Anesthesia preparation time, length of surgery, anesthesia-related time in the operating room, time to sit, and time to walk were significantly low in Group GA (p < 0.05, whereas time to fast-track eligibility, length of stay in the PACU, discharge time, and other parameters were similar in both of the groups. CONCLUSION: While anesthesia preparation time, length of surgery, start time of surgery, time to sit, and time to walk were shorter in the General Anesthesia group, time to fast-track eligibility, phase 1 recovery time, and discharge time were similar among patients subjected to selective spinal anesthesia.

Aberrant TRPV1 expression in heat hyperalgesia associated with trigeminal neuropathic pain.

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Urano, Hiroko; Ara, Toshiaki; Fujinami, Yoshiaki; Hiraoka, B Yukihiro

2012-01-01

Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1) in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL) model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP) were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

Remifentanil analgesia during external cephalic version for breech presentation in nulliparous women at term

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Wang, Zhi-Hong; Yang, Yi; Xu, Gui-Ping

2017-01-01

Abstract Background: The aim of the study was to assess the efficacy and safety of remifentanil for pain relief during external cephalic version (ECV) for breech presentation in nulliparous women at term. Methods: A total of 144 nulliparous women with singleton breech presentation were randomly divided into the intervention group and the placebo group, with 72 subjects in each group. The subjects in the intervention group received remifentanil (infused at 0.1 μg kg–1 min–1 with demand boluses of 0.1 μg/kg), whereas those in the placebo group were given saline placebo. This study was conducted from May 2013 to April 2016. The outcomes measures include pain (measured with the visual analog scale, VAS), success rate of ECV, maternal satisfaction for ECV, and adverse events. Results: A total of 137 participants completed the study. The intervention with remifentanil showed greater efficacy than did placebo in decreasing the VAS score immediately after ECV (intervention group 4.3 ± 2.2 vs placebo group 6.4 ± 2.5, P < 0.01). A significant difference in the ECV success rate was also found between the 2 groups (intervention group 56.9% vs placebo group 38.9%, P = 0.03). In addition, a significant difference in the satisfaction score was also detected (intervention group 9.3 ± 0.9 vs placebo group 6.7 ± 1.2, P < 0.01). The observed adverse events were similar between the 2 groups. Conclusion: This study shows that remifentanil could decrease pain, improve the ECV success rate, and improve satisfaction in nulliparous women at term during the period of ECV. Furthermore, it is also well tolerated with few adverse events. PMID:28296735

Cold hyperalgesia as a prognostic factor in whiplash associated disorders: a systematic review.

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Goldsmith, Robert; Wright, Chris; Bell, Sarah F; Rushton, Alison

2012-10-01

To review and critically evaluate the existing literature for the prognostic value of cold hyperalgesia in Whiplash Associated Disorders (WAD). Embase, PsycINFO, and Medline databases were systematically searched (from inception to 20th September 2011) for prospective studies investigating a prognostic ability for cold hyperalgesia in WAD. Reference lists and lead authors were cross-referenced. Two independent reviewers selected studies, and consensus was achieved via a third reviewer. The risk of bias in identified studies was systematically evaluated by two reviewers using previously published guidance. The influences of seven potential covariates of cold hyperalgesia were considered. Quantitative synthesis was planned and homogeneity assessed. A modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to qualitatively assess trials. The review screened 445 abstracts, from these 20 full text studies were retrieved and assessed for eligibility. Six prospective studies on four cohorts were identified and reviewed. Findings from all four cohorts supported cold hyperalgesia as a prognostic factor in WAD. There is moderate evidence supporting cold hyperalgesia as a prognostic factor for long-term pain and disability outcome in WAD. Further validation of the strength of this relationship and the influence of covariates are required. The mechanism for this relationship is unknown. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of Remifentanil with Liquid Chromatography-Tandem Mass Spectrometry and an Extensive Stability Investigation in EDTA Whole Blood and Acidified EDTA Plasma

NARCIS (Netherlands)

Koster, Remco A.; Vereecke, Hugo E. M.; Greijdanus, Ben; Touw, Daan J.; Struys, Michel M. R. F.; Alffenaar, Jan Willem C.

BACKGROUND: Remifentanil is a mu-opioid receptor agonist that was developed as a synthetic opioid for use in anesthesia and intensive care medicine. Remifentanil is rapidly metabolized in both blood and tissues, which results in a very short duration of action. Even after blood sampling,

[Effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients after target-controlled induction].

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Zheng, Xiaochun; Wan, Liling; Gao, Fei; Chen, Jianghu; Tu, Wenshao

2017-08-12

To observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS). Fifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO 12 ), Pizhixia (AT 4 ), and Shenmen (TF 4 ) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5μg/L and increased by 0.3μg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0μg/L and increased by 0.3μg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T 0 (entering into the operation room), T 1 (losing consciousness) and T 2 (pain relief), the plasma and effect site concentrations of propofol at T 1 , the plasma and effect site concentrations of remifentanil at T 2 . After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time. At T 1 and T 2 , MAP and HR of the observation group were higher than those of the control group ( P effect site concentrations of propofol in the observation group were significantly lower than those in the control group

Increased pain relief with remifentanil does not improve the success rate of external cephalic version: a randomized controlled trial.

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Burgos, Jorge; Pijoan, José I; Osuna, Carmen; Cobos, Patricia; Rodriguez, Leire; Centeno, María del Mar; Serna, Rosa; Jimenez, Antonia; Garcia, Eugenia; Fernandez-Llebrez, Luis; Melchor, Juan C

2016-05-01

Our objective was to compare the effect of two pain relief methods (remifentanil vs. nitrous oxide) on the success rate of external cephalic version. We conducted a randomized open label parallel-group controlled single-center clinical trial with sequential design, at Cruces University Hospital, Spain. Singleton pregnancies in noncephalic presentation at term that were referred for external cephalic version were assigned according to a balanced (1:1) restricted randomization scheme to analgesic treatment with remifentanil or nitrous oxide during the procedure. The primary endpoint was external cephalic version success rate. Secondary endpoints were adverse event rate, degree of pain, cesarean rate and perinatal outcomes. The trial was stopped early after the second interim analysis due to a very low likelihood of finding substantial differences in efficacy (futility). The external cephalic version success rate was the same in the two arms (31/60, 51.7%) with 120 women recruited, 60 in each arm. The mean pain score was significantly lower in the remifentanil group (3.2 ± 2.4 vs. 6.0 ± 2.3; p external cephalic version-related complications. There was a trend toward a higher frequency of adverse effects in the remifentanil group (18.3% vs. 6.7%, p = 0.10), with a significantly higher incidence rate (21.7 events/100 women vs. 6.7 events/100 women with nitrous oxide, p = 0.03). All reported adverse events were mild and reversible. Remifentanil for analgesia decreased external cephalic version-related pain but did not increase the success rate of external cephalic version at term and appeared to be associated with an increased frequency of mild adverse effects. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Effect-site concentration of remifentanil for preventing cough during emergence in elderly patients undergoing nasal surgery: a comparison with adult patients

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Yoo JY

2016-09-01

Full Text Available Ji Young Yoo,1 Jong Yeop Kim,1 Hyun Jeong Kwak,2 Dong Chul Lee,2 Go Wun Kim,1 Sook Young Lee,1 Yun Jeong Chae1 1Department of Anaesthesiology and Pain Medicine, Ajou University School of Medicine, Suwon, 2Department of Anaesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon, Korea Purpose: Prevention of cough during emergence after nasal surgery is important for avoiding surgical site bleeding. We investigated the remifentanil effect-site concentration in 50% (EC50 of the elderly patients undergoing nasal surgery for smooth emergence without cough and compared it with that of adult patients.Methods: Twenty-two elderly (aged 65–80 years and 25 adult patients (aged 20–60 years with an American Society of Anesthesiologists physical status I/II undergoing nasal surgery were enrolled. Anesthesia was maintained with sevoflurane and remifentanil. Remifentanil EC50 and EC95 for preventing cough were determined using the modified Dixon’s up-and-down method and isotonic regression with bootstrapping approach. Recovery profiles were also recorded.Results: With Dixon’s up-and-down method, the EC50 of remifentanil in elderly patients (2.40±0.25 ng/mL was not significantly different from that of adults (2.33±0.30 ng/mL (P=0.687. With isotonic regression, the EC95 of remifentanil in elderly patients (3.32 [95% confidence interval: 3.06–3.38] ng/mL was not significantly different from that of adults (3.30 [95% confidence interval: 2.96–3.37] ng/mL. However, eye opening time (14.1±3.8 vs 12.0±2.9 seconds, extubation time (17.2±4.1 vs 14.0±3.0 seconds, and postanesthesia care unit duration (44.5±7.6 vs 38.7±3.4 minutes in elderly patients were significantly longer than those in adults (P<0.05.Conclusion: Remifentanil EC50 for preventing cough after nasal surgery with sevoflurane anesthesia did not differ between elderly and adult patients. However, delayed awakening and respiratory adverse events may warrant attention

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles: A consort compliant article.

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Kim, Dong-Ho; Choi, June Young; Kim, Byoung-Gook; Hwang, Jin-Young; Park, Seong-Joo; Oh, Ah-Young; Jeon, Young-Tae; Ryu, Jung-Hee

2016-12-01

Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy. Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively. Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events.

Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.

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Ohri, Rachit; Wang, Jeffery Chi-Fei; Pham, Lan; Blaskovich, Phillip D; Costa, Daniel; Nichols, Gary; Hildebrand, William; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary R

2014-01-01

Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery. Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days. Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated

Effect of propofol and remifentanil on cerebral perfusion and oxygenation in pigs

DEFF Research Database (Denmark)

Mikkelsen, Mai Louise Grandsgaard; Ambrus, Rikard; Miles, James Edward

2016-01-01

The objective of this review is to evaluate the existing literature with regard to the influence of propofol and remifentanil total intravenous anaesthesia (TIVA) on cerebral perfusion and oxygenation in healthy pigs. Anaesthesia has influence on cerebral haemodynamics and it is important not onl...

Effect of a high-dose target-controlled naloxone infusion on pain and hyperalgesia in patients following groin hernia repair: study protocol for a randomized controlled trial

DEFF Research Database (Denmark)

Pereira, Manuel Pedro; Utke Werner, Mads; Berg Dahl, Joergen

2015-01-01

no volunteer developed significant secondary hyperalgesia after the placebo infusion. In order to consistently demonstrate latent sensitization in humans, a pain model inducing deep tissue inflammation, as used in animal studies, might be necessary. The aim of the present study is to examine whether a high......-dose target-controlled naloxone infusion can reinstate pain and hyperalgesia following recovery from open groin hernia repair and thus consistently demonstrate opioid-mediated latent sensitization in humans. METHODS/DESIGN: Patients submitted to unilateral, primary, open groin hernia repair will be included...

Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

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Kopruszinski, Caroline M; Reis, Renata C; Bressan, Elisangela; Reeh, Peter W; Chichorro, Juliana G

2015-09-05

Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects. Copyright © 2015. Published by Elsevier B.V.

Analysis of clothing and urine from Moscow theatre siege casualties reveals carfentanil and remifentanil use.

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Riches, James R; Read, Robert W; Black, Robin M; Cooper, Nicholas J; Timperley, Christopher M

2012-01-01

On October 26, 2002, Russian Special Forces deployed a chemical aerosol against Chechen terrorists to rescue hostages in the Dubrovka theatre. Its use confirmed Russian military interest in chemicals with effects on personnel and caused 125 deaths through a combination of the aerosol and inadequate medical care. This study provides evidence from liquid chromatography-tandem mass spectrometry analysis of extracts of clothing from two British survivors, and urine from a third survivor, that the aerosol comprised a mixture of two anaesthetics--carfentanil and remifentanil--whose relative proportions this study was unable to identify. Carfentanil and remifentanil were found on a shirt sample and a metabolite called norcarfentanil was found in a urine sample. This metabolite probably originated from carfentanil.

Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats.

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Hofford, Rebecca S; Chow, Jonathan J; Beckmann, Joshua S; Bardo, Michael T

2017-12-01

Opioid abuse is a major problem around the world. Identifying environmental factors that contribute to opioid abuse and addiction is necessary for decreasing this epidemic. In rodents, environmental enrichment protects against the development of low dose stimulant self-administration, but studies examining the effect of enrichment and isolation (compared to standard housing) on the development of intravenous opioid self-administration have not been conducted. The present study investigated the role of environmental enrichment on self-administration of the short-acting μ-opioid remifentanil. Rats were raised in an enriched condition (Enr), standard condition (Std), or isolated condition (Iso) beginning at 21 days of age and were trained to lever press for 1 or 3 μg/kg/infusion remifentanil in young adulthood. Acquisition of self-administration and responding during increasing fixed ratio requirements were assessed, and a dose-response curve was generated. In all phases, Enr rats lever pressed significantly less than Std and Iso rats, with Enr rats pressing between 9 and 40% the amount of Iso rats. Enr rats did not acquire remifentanil self-administration when trained with 1 μg/kg/infusion, did not increase responding over increasing FR when trained at either dose, and their dose-response curves were flattened compared to Std and Iso rats. When expressed as economic demand curves, Enr rats displayed a decrease in both essential value (higher α) and reinforcer intensity (Q 0 ) compared to Std and Iso rats at the 1 μg/kg/infusion training dose. Environmental enrichment reduced remifentanil intake, suggesting that social and environmental novelty may protect against opioid abuse.

Remifentanil: o regime de infusão faz diferença na prevenção das respostas circulatórias à intubação traqueal? Remifentanil: ¿el régimen de infusión es la diferencia en la prevención de las respuestas circulatorias a la intubación traqueal? Remifentanil: does the infusion regimen make a difference in the prevention of hemodynamic responses to tracheal intubation?

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Fernando Squeff Nora

2007-06-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: Os opióides em doses elevadas diminuem a resposta circulatória à intubação traqueal. Entretanto, o lento perfil de recuperação dos opióides tradicionais pode limitar a utilização em altas doses. O remifentanil possui tempo de início e de término de ação rápidos e previsíveis, o que o diferencia dos demais. O objetivo primário deste estudo foi verificar a hipótese de que não há necessidade de iniciar a administração de remifentanil antes da indução com o propofol. MÉTODO: Foram avaliados 30 pacientes, divididos em dois grupos, que receberam anestesia geral venosa total. No Grupo 1, a infusão de remifentanil (0,3 µg.kg-1.min-1 foi iniciada dois minutos antes da indução e, no Grupo 2, juntamente com a indução. Foram avaliadas as pressões arteriais sistólica, diastólica e média (PAS, PAD, PAM, freqüência cardíaca (FC, concentrações no local efetor de propofol (CEF-prop e de remifentanil (CEF-remi em três momentos: basal (M0; após a perda do contato verbal (M1; e após a intubação traqueal (M2. RESULTADOS: As pressões arteriais apresentaram reduções significativas em ambos os grupos, em M1 e M2. A CEF-remi foi maior no Grupo 1, em M1 e maior, no Grupo 2, em M2 (p JUSTIFICATIVA Y OBJETIVOS: Los opioides en dosis elevadas disminuyen la respuesta circulatoria a la intubación traqueal. Sin embargo, el lento perfil de recuperación de los opioides tradicionales puede limitar la utilización en altas dosis. El remifentanil posee tiempo de inicio y de término de acción rápidos y previsibles, lo que lo diferencia de los demás. El objetivo primario de este estudio fue verificar la hipótesis de que no hay necesidad de iniciar la administración de remifentanil antes de la inducción con el propofol. MÉTODO: Fueron evaluados 30 pacientes, divididos en dos grupos, que recibieron anestesia general intravenosa total. En el Grupo 1, la infusión de remifentanil (0,3 µg.kg-1.min-1 se

Influence of clonidine and ketamine on m-RNA expression in a model of opioid-induced hyperalgesia in mice.

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Henning Ohnesorge

Full Text Available We investigated the influence of morphine and ketamine or clonidine in mice on the expression of genes that may mediate pronociceptive opioid effects.C57BL/6 mice received morphine injections thrice daily using increasing doses (5-20 mg∙kg(-1 for 3 days (sub-acute, n=6 or 14 days (chronic, n=6 and additionally either s-ketamine (5 mg∙kg(-1, n=6 or clonidine (0.1 mg∙kg(-1, n=6. Tail flick test and the assessment of the mechanical withdrawal threshold of the hindpaw was performed during and 4 days after cessation of opioid treatment. Upon completion of the behavioural testing the mRNA-concentration of the NMDA receptor (NMDAR1 and β-arrestin 2 (Arrb2 were measured by PCR.Chronic opioid treatment resulted in a delay of the tail flick latency with a rapid on- and offset. Simultaneously the mice developed a static mechanical hyperalgesia with a delayed onset that that outlasted the morphine treatment. Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Coadministration of s-ketamine or clonidine resulted in a reversal of the mechanical hyperalgesia and inhibited the normalization of NMDAR1 mRNA expression but had no effect on the expression of Arrb2 mRNA.In the model of chronic morphine therapy the antinociceptive effects of morphine are represented by the thermal analgesia while the proniceptive effects are represented by the mechanical hyperalgesia. The results indicate that the regulation of the expression of NMDAR1 and Arrb2 may be associated to the development of OIH in mice.The results indicate that co-administration of clonidine or ketamine may influence the underlying mechanisms of OIH.

Pretreatment with remifentanil, fentanyl, or lidocaine to prevent withdrawal after rocuronium using venous occlusion technique in children and adolescents: a prospective randomized placebo-controlled double-blind study.

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Abu-Halaweh, S A; Aloweidi, A K; Qudaisat, I Y; Al-Hussami, M O; Al Zaben, K R; Abu-Halaweh, A S

2014-12-01

Pain caused by intravenous injection of the muscle relaxant rocuronium bromide is common in children and adolescents. The cause of this unwanted effect is still unclear, and different pretreatment drugs have been administered in attempts to alleviate this side effect, with varying degrees of success. This study used a 60-s venous occlusion technique to evaluate the effectiveness of pretreatment with lidocaine, fentanyl, or remifentanil in preventing pain-induced withdrawal caused by intravenous injection of rocuronium bromide during the induction of general anesthesia. One hundred and one child and adolescent patients, ASA Ι-II, requiring various surgical procedures under general anesthesia with muscle relaxation and mechanical ventilation, were enrolled. Patients were allocated randomly using computer-generated randomization into one of four pretreatment groups: a remifentanil group (1 µg/kg, n = 25), fentanyl group (1 µg/kg, n = 26), lidocaine 1% group (0.5 mg/kg, n = 25), and normal saline group (n = 25). Drug doses were prepared in normal saline to a total volume of 5 ml. Venous occlusion was applied 10 cm above the venous access site. Pretreatment drugs were injected and retained for 60 s at the site of injection by an anesthetist blinded to group allocation. After release of the tourniquet, rocuronium (0.5 mg/kg) was then injected over 5 s, and withdrawal was recorded by another anesthetist blinded to group allocation. Descriptive statistics, analysis of variance, and a chi-squared test were used to statistically analyze the results as appropriate. Compared to normal saline, all other pretreatment groups scored a significantly lower mean of withdrawal response (P rocuronium injection. Remifentanil was superior to fentanyl in suppressing the withdrawal response caused by rocuronium injection (P rocuronium injection in children and adolescents. Lidocaine was superior to remifentanil which, in turn, was more effective than fentanyl.

Patient controlled analgesia with remifentanil versus epidural analgesia in labour : randomised multicentre equivalence trial

NARCIS (Netherlands)

Freeman, Liv M; Bloemenkamp, Kitty W; Franssen, Maureen T; Papatsonis, Dimitri N; Hajenius, Petra J; Hollmann, Markus W; Woiski, Mallory D; Porath, Martina; van den Berg, Hans J; van Beek, Erik; Borchert, Odette W H M; Schuitemaker, Nico; Sikkema, J Marko; Kuipers, A H M; Logtenberg, Sabine L M; van der Salm, Paulien C M; Oude Rengerink, Katrien; Lopriore, Enrico; van den Akker-van Marle, M Elske; le Cessie, Saskia; van Lith, Jan M; Struys, Michel M; Mol, Ben Willem J; Dahan, Albert; Middeldorp, Johanna M; Oude Rengerink, K

2015-01-01

OBJECTIVE: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. DESIGN: Multicentre randomised controlled equivalence trial. SETTING: 15 hospitals in the Netherlands. PARTICIPANTS: Women with an

Patient controlled analgesia with remifentanil versus epidural analgesia in labour : randomised multicentre equivalence trial

NARCIS (Netherlands)

Freeman, Liv M.; Bloemenkamp, Kitty W.; Franssen, Maureen T.; Papatsonis, Dimitri N.; Hajenius, Petra J.; Hollmann, Markus W.; Woiski, Mallory D.; Porath, Martina; van den Berg, Hans J.; van Beek, Erik; Borchert, Odette W. H. M.; Schuitemaker, Nico; Sikkema, J. Marko; Kuipers, A. H. M.; Logtenberg, Sabine L. M.; van der Salm, Paulien C. M.; Rengerink, Katrien Oude; Lopriore, Enrico; van den Akker-van Marle, M. Elske; le Cessie, Saskia; van Lith, Jan M.; Struys, Michel M.; Mol, Ben Willem J.; Dahan, Albert; Middeldorp, Johanna M.

2015-01-01

Objective To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Design Multicentre randomised controlled equivalence trial. Setting 15 hospitals in the Netherlands. Participants Women with an

Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial

NARCIS (Netherlands)

Freeman, L.M.; Bloemenkamp, K.W.; Franssen, M.T.; Papatsonis, D.N.; Hajenius, P.J.; Hollmann, M.W.; Woiski, M.D.; Porath, M.; Berg, H.J. van den; Beek, E. van; Borchert, O.W.; Schuitemaker, N.; Sikkema, J.M.; Kuipers, A.H.; Logtenberg, S.L.; Salm, P.C. van der; Oude Rengerink, K.; Lopriore, E.; Akker-van Marle, M.E. van den; Cessie, S. le; Lith, J.M. van; Struys, M.M.; Mol, B.W.; Dahan, A; Middeldorp, J.M.

2015-01-01

OBJECTIVE: To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. DESIGN: Multicentre randomised controlled equivalence trial. SETTING: 15 hospitals in the Netherlands. PARTICIPANTS: Women with an

Dexmedetomidine versus Remifentanil for Sedation during Awake Fiberoptic Intubation

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Davide Cattano

2012-01-01

Full Text Available This study compared remifentanil and dexmedetomidine as awake fiberoptic intubation (AFOI anesthetics. Thirty-four adult ASA I-III patients were enrolled in a double-blinded randomized pilot study to receive remifentanil (REM or dexmedetomidine (DEX for sedation during AFOI (nasal and oral. Thirty patients completed the study and received 2 mg midazolam IV and topical anesthesia. The REM group received a loading dose of 0.75 mcg/kg followed by an infusion of 0.075 mcg/kg/min. The DEX group received a loading dose of 0.4 mcg/kg followed by an infusion of 0.7 mcg/kg/hr. Time to sedation, number of intubation attempts, Ramsay sedation scale (RSS score, bispectral index (BIS, and memory recall were recorded. All thirty patients were successfully intubated by AFOI (22 oral intubations/8 nasal. First attempt success rate with AFOI was higher in the REM group than the DEX group, 72% and 38% (P=0.02, respectively. The DEX group took longer to attain RSS of ≥3 and to achieve BIS <80, as compared to the REM group. Postloading dose verbal recall was poorer in the DEX group. Dexmedetomidine seems a useful adjunct for patients undergoing AFOI but is dependent on dosage and time. Further studies in the use of dexmedetomidine for AFOI are warranted.

Labour pain with remifentanil patient-controlled analgesia versus epidural analgesia : a randomised equivalence trial

NARCIS (Netherlands)

Logtenberg, Slm; Oude Rengerink, K; Verhoeven, C J; Freeman, L M; van den Akker, Esa; Godfried, M B; van Beek, E; Borchert, Owhm; Schuitemaker, N; van Woerkens, Ecsm; Hostijn, I; Middeldorp, J M; van der Post, J A; Mol, B W

OBJECTIVE: To distinguish satisfaction with pain relief using remifentanil patient-controlled analgesia (RPCA) compared with epidural analgesia (EA) in low-risk labouring women. DESIGN: Randomised controlled equivalence trial. SETTING: Eighteen midwifery practices and six hospitals in the

Prediction of Bispectral Index during Target-controlled Infusion of Propofol and Remifentanil: A Deep Learning Approach.

Science.gov (United States)

Lee, Hyung-Chul; Ryu, Ho-Geol; Chung, Eun-Jin; Jung, Chul-Woo

2018-03-01

The discrepancy between predicted effect-site concentration and measured bispectral index is problematic during intravenous anesthesia with target-controlled infusion of propofol and remifentanil. We hypothesized that bispectral index during total intravenous anesthesia would be more accurately predicted by a deep learning approach. Long short-term memory and the feed-forward neural network were sequenced to simulate the pharmacokinetic and pharmacodynamic parts of an empirical model, respectively, to predict intraoperative bispectral index during combined use of propofol and remifentanil. Inputs of long short-term memory were infusion histories of propofol and remifentanil, which were retrieved from target-controlled infusion pumps for 1,800 s at 10-s intervals. Inputs of the feed-forward network were the outputs of long short-term memory and demographic data such as age, sex, weight, and height. The final output of the feed-forward network was the bispectral index. The performance of bispectral index prediction was compared between the deep learning model and previously reported response surface model. The model hyperparameters comprised 8 memory cells in the long short-term memory layer and 16 nodes in the hidden layer of the feed-forward network. The model training and testing were performed with separate data sets of 131 and 100 cases. The concordance correlation coefficient (95% CI) were 0.561 (0.560 to 0.562) in the deep learning model, which was significantly larger than that in the response surface model (0.265 [0.263 to 0.266], P deep learning model-predicted bispectral index during target-controlled infusion of propofol and remifentanil more accurately compared to the traditional model. The deep learning approach in anesthetic pharmacology seems promising because of its excellent performance and extensibility.

[Effect of rocuronium administration rate and remifentanil on prevention of rocuronium injection pain in pediatric cases].

Science.gov (United States)

Şimşek Ülkü, Hatice; Güneş, Yasemin; Ilgınel, Murat; Biricik, Ebru; Karacaer, Feride

2017-10-01

In this study, we aimed to determine the effect of remifentanil administration prior to slow and fast rocuronium infusion on hemodynamic changes and rocuronium injection pain in pediatric patients. In total, 120 5-15-year-old ASA score I/II pediatric patients were included in the study. Group A: slow rocuronium injection-saline; group B: slow rocuronium injection (0.6 mg/kg IV)-remifentanyl; group C: fast rocuronium injection-saline; and group D: fast rocuronium injection-remifentanyl. Withdrawal movement after rocuronium injection was recorded based on a 3-point response to withdrawal score. Hemodynamic parameters were recorded. One minute after rocuronium injection, HR values were found to be lower in remifentanil groups (p: 0.0001; 101.4±22.1, p: 0.003; 99.8±18.3 in group B and D, respectively) compared with those in placebo groups (p: 0.025; 107.4±21.7, p: 0.012; 114.0±16.4 in group A and C, respectively). With respect to the response to withdrawal scores, unresponsiveness rates were the highest in group B (66.7%) and group D (70%). The number of non-responder patients was 9 in saline-administered groups (group A and C), whereas it was 20 and 21 in remifentanil-administered groups (group B and D, respectively). Generalized responses were observed predominantly in groups A (20%) and C (20%). Generalized responses were highest in groups A (20%, n=6) and C (20%, n=6). There was no impact of infusion speed on rocuronium injection pain in pediatric cases, whereas it is concluded that remifentanil administration prior to rocuronium injection considerably reduced rocuronium injection pain regardless of injection speed and without serious hemodynamic changes.

Cold Pain Threshold Identifies a Subgroup of Individuals With Knee Osteoarthritis That Present With Multimodality Hyperalgesia and Elevated Pain Levels

OpenAIRE

Wright, Anthony; Benson, Heather A.E.; Will, Rob; Moss, Penny

2017-01-01

Objectives: Cold hyperalgesia has been established as an important marker of pain severity in a number of conditions. This study aimed to establish the extent to which patients with knee osteoarthritis (OA) demonstrate widespread cold, heat, and pressure hyperalgesia. OA participants with widespread cold hyperalgesia were compared with the remaining OA cohort to determine whether they could be distinguished in terms of hyperalgesia, pain report, pain quality, and physical function. Methods: A...

IB4(+) nociceptors mediate persistent muscle pain induced by GDNF.

Science.gov (United States)

Alvarez, Pedro; Chen, Xiaojie; Bogen, Oliver; Green, Paul G; Levine, Jon D

2012-11-01

Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1-10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E(2) at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.

Opioids and immunosupression in oncological postoperative patients

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José Luis Bonilla-García

Full Text Available Summary Introduction: Recent animal studies demonstrated immunosuppressive effects of opioid withdrawal resulting in a higher risk of infection. The aim of this study was to determine the impact of remifentanil discontinuation on Post-Anesthesia Care Unit (PACU-acquired infection after a schedule of sedoanalgesia of at least 6 days. Method: All patients over 18 years of age with a unit admission of more than 4 days were consecutively selected. The study population was the one affected by surgical pathology of any origin where sedation was based on any hypnotic and the opioid remifentanil was used as analgesic for at least 96 hours in continuous perfusion. Patients who died during admission to the unit and those with combined analgesia (peripheral or neuroaxial blocks were excluded. Bivariate analysis was performed to determine risk factors for infection acquired in the unit. A comparative study between periods of 6 days before and after the cessation of remifentanil was performed. Paired samples test and McNemar test was used for quantitative and categorical variables, respectively. Results: There were 1,789 patients admitted to the PACU during the study and the population eligible was constituted for 102 patients. The incidence rate of PACU-acquired infection was 38 per 1,000 PACU days. Ventilator-associated pneumonia was the most frequently diagnosed PACU-acquired infection. Pseudomona aeruginosa was the most frequently isolated microorganism. Hospital mortality was 36.27%. No statistically significant differences were seen in the incidence of HAI in cancer patients in relation to discontinuation of remifentanil (p=0.068. Conclusion: The baseline state of immunosuppression of cancer patients does not imply a higher incidence of HAI in relation to the interruption of remifentanil. It would be of interest to carry out a multicenter PACU study that included immunological patterns.

Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

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Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

2010-04-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

Intravenous Remifentanil Analgaesia for an Obstetric Patient with Type I Neurofibromatosis and a Factor V Leiden Mutation

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José L. Gálvez

2018-01-01

Full Text Available Type I neurofibromatosis is characterised by altered skin pigmentation and the growth of benign tumours, particularly along the peripheral nerves and central nervous system. We report a 36-year-old primigravida woman in labour who was admitted to the obstetric suite of the Hospital Sant Joan de Déu, Barcelona, Spain, in 2007 with hypothyroidism, type I neurofibromatosis and a factor V Leiden mutation. Due to a lack of cranial and spinal imaging data, an epidural was not indicated; instead, continuous intravenous remifentanil analgaesia was administered. The remifentanil infusion was self-titrated by the patient using a visual analogue scale, with the dosage ranging from 0.01 to 0.25 μg/kg/minute. Due to rotational dystocia, Kjelland-type forceps were used during the delivery. After birth, the infant was found to have Apgar scores of 9 and 10, with no maternal or neonatal adverse effects observed. Although still controversial, remifentanil may be a successful alternative for analgaesia in similar cases; however, the specific risks and benefits for each patient should be considered prior to administration.

Remifentanil for labour analgesia: a double-blinded, randomised controlled trial of maternal and neonatal effects of patient-controlled analgesia versus continuous infusion.

Science.gov (United States)

Shen, M K; Wu, Z F; Zhu, A B; He, L L; Shen, X F; Yang, J J; Feng, S W

2013-03-01

This trial aimed to compare the maternal and neonatal effects of remifentanil given by patient-controlled analgesia (PCA) or continuous infusion for labour analgesia. Patient controlled analgesia was administered using increasing stepwise boluses from 0.1 to 0.4 μg.kg(-1) (0.1 μg.kg(-1) increment, 2 min lockout, n = 30). Continuous infusion used rates from 0.05 to 0.2 μg.kg(-1) .min(-1) (0.05 μg.kg(-1) .min(-1) increment, n = 30). Dose increments were given on request. Women reported lowest pain scores (median (IQR [range]) of 3 (2-4 [2-5]) for PCA and 4 (3-5.25 [3-7]) for continuous infusion (p = 0.004) at 60 min after the beginning of analgesia. The mean (SD) remifentanil umbilical vein/maternal artery ratio in the PCA and infusion groups were 0.74 (0.45) vs 0.70 (0.52), respectively (p = 0.776). The mean (SD) umbilical artery/umbilical vein ratios were 0.31 (0.12) vs 0.26 (0.07), respectively (p = 0.088). Maternal and neonatal adverse reactions of remifentanil were similar between the two groups. The total remifentanil consumption (median (IQR [range]) during PCA administration was lower than continuous infusion, 1.34 (1.22-1.48 [0.89-1.69]) mg vs 1.49 (1.35-1.61 [1.12-1.70] mg; p = 0.011). The results suggest that remifentanil PCA provides better pain relief and similar placental transfer compared with continuous infusion. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Concomitant administration of nitrous oxide and remifentanil reduces oral tissue blood flow without decreasing blood pressure during sevoflurane anesthesia in rabbits.

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Kasahara, Masataka; Ichinohe, Tatsuya; Okamoto, Sota; Okada, Reina; Kanbe, Hiroaki; Matsuura, Nobuyuki

2015-06-01

To determine whether continuous administration of nitrous oxide and remifentanil—either alone or together—alters blood flow in oral tissues during sevoflurane anesthesia. Eight male tracheotomized Japanese white rabbits were anesthetized with sevoflurane under mechanical ventilation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), common carotid arterial blood flow (CCBF), tongue mucosal blood flow (TMBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF) were recorded in the absence of all test agents and after administration of the test agents (50 % nitrous oxide, 0.4 μg/kg/min remifentanil, and their combination) for 20 min. Nitrous oxide increased SBP, DBP, MAP, CCBF, BBF, MBF, UBF, and LBF relative to baseline values but did not affect HR or TMBF. Remifentanil decreased all hemodynamic variables except DBP. Combined administration of nitrous oxide and remifentanil recovered SBP, DBP, MAP, and CCBF to baseline levels, but HR and oral tissue blood flow remained lower than control values. Our findings suggest that concomitant administration of nitrous oxide and remifentanil reduces blood flow in oral tissues without decreasing blood pressure during sevoflurane anesthesia in rabbits.

Patient controlled analgesia with remifentanil versus epidural analgesia in labour: randomised multicentre equivalence trial

NARCIS (Netherlands)

Freeman, Liv M.; Bloemenkamp, Kitty W.; Franssen, Maureen T.; Papatsonis, Dimitri N.; Hajenius, Petra J.; Hollmann, Markus W.; Woiski, Mallory D.; Porath, Martina; van den Berg, Hans J.; van Beek, Erik; Borchert, Odette W. H. M.; Schuitemaker, Nico; Sikkema, J. Marko; Kuipers, A. H. M.; Logtenberg, Sabine L. M.; van der Salm, Paulien C. M.; Oude Rengerink, Katrien; Lopriore, Enrico; van den Akker-van Marle, M. Elske; le Cessie, Saskia; van Lith, Jan M.; Struys, Michel M.; Mol, Ben Willem J.; Dahan, Albert; Middeldorp, Johanna M.

2015-01-01

To determine women's satisfaction with pain relief using patient controlled analgesia with remifentanil compared with epidural analgesia during labour. Multicentre randomised controlled equivalence trial. 15 hospitals in the Netherlands. Women with an intermediate to high obstetric risk with an

Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats.

Science.gov (United States)

de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel

2016-01-01

Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals' nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3-L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals' nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression.

Remifentanil in the intensive care unit: tolerance and acute withdrawal syndrome after prolonged

NARCIS (Netherlands)

Delvaux, B.; Ryckwaert, Y.; Boven, van R.M.; Kock, M.; Capdevila, X.

2005-01-01

SEDATION in the intensive care unit should be minimized to reduce the duration of mechanical ventilation and its related complications.1 The drug regimen would ideally allow rapid awakening, to perform neurologic and respiratory evaluation on a daily basis.2,3 In this context, remifentanil, with its

Hyperalgesia in a human model of acute inflammatory pain: a methodological study

DEFF Research Database (Denmark)

Pedersen, J L; Kehlet, H

1998-01-01

as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...

The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide.

Science.gov (United States)

Mao, Xiaoyan; Wang, Yuedong; Carter, Andrew V; Zhen, Xuechu; Guo, Sun-Wei

2011-10-01

Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.

Avaliação da hiperalgesia e alterações histológicas do gânglio da raiz dorsal induzidas pelo núcleo pulposo Evaluation of hyperalgesia and histological changes of dorsal root ganglion induced by nucleus pulposus

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André Luiz de Souza Grava

2010-01-01

estruturas do gânglio da raiz dorsal e apresentaram aumento da intensidade nos períodos mais longos de observação.OBJECTIVE: To evaluate hyperalgesia and histological changes of dorsal root ganglia induced by nucleus pulposus (NP contact. METHODS: Twenty Wistar rats were used, divided into two experimental groups. In one of the groups, a fragment of the autologous NP was removed from the sacroccocigeal region and deposited on the L5 dorsal root ganglia. In the control group, the NP was removed from the sacrococcygeal region, L5 dorsal root ganglia were exposed and covered by a piece of adipous fat tissue. Hyperalgesia was evaluated by the von Frey electronic test and Hargreaves test, and histological changes of the dorsal root ganglia by HE staining and immunohistochemistry using iNOS. The evaluation of hyperalgesia and histological changes of the dorsal root ganglia were performed on the third postoperative day and after 1, 3, 5, and 7 weeks. RESULTS: NP induced higher intensity mechanical and thermal hyperalgesia. Dorsal root ganglia in contact with nucleus pulposus presented histological changes and the intensity of these changes were proportional to the length of time in contact. The expression of iNOS was higher in the glial cells in contact with the nucleus pulposus. CONCLUSION: The contact of nucleus pulposus with dorsal root ganglia induced histological changes and mechanical and thermal hyperalgesia. These changes were more intense after longer period of evaluation.

Computerized tests to evaluate recovery of cognitive function after deep sedation with propofol and remifentanil for colonoscopy.

Science.gov (United States)

Borrat, Xavier; Ubre, Marta; Risco, Raquel; Gambús, Pedro L; Pedroso, Angela; Iglesias, Aina; Fernandez-Esparrach, Gloria; Ginés, Àngels; Balust, Jaume; Martínez-Palli, Graciela

2018-03-27

The use of sedation for diagnostic procedures including gastrointestinal endoscopy is rapidly growing. Recovery of cognitive function after sedation is important because it would be important for most patients to resume safe, normal life soon after the procedure. Computerized tests have shown being accurate descriptors of cognitive function. The purpose of the present study was to evaluate the time course of cognitive function recovery after sedation with propofol and remifentanil. A prospective observational double blind clinical study conducted in 34 young healthy adults undergoing elective outpatient colonoscopy under sedation with the combination of propofol and remifentanil using a target controlled infusion system. Cognitive function was measured using a validated battery of computerized cognitive tests (Cogstate™, Melbourne, Australia) at different predefined times: prior to starting sedation (Tbaseline), and then 10 min (T10), 40 min (T40) and 120 min (T120) after the end of colonoscopy. Tests included the assessment of psychomotor function, attention, visual memory and working memory. All colonoscopies were completed (median time: 26 min) without significant adverse events. Patients received a median total dose of propofol and remifentanil of 149 mg and 98 µg, respectively. Psychomotor function and attention declined at T10 but were back to baseline values at T40 for all patients. The magnitude of psychomotor task reduction was large (d = 0.81) however 100% of patients were recovered at T40. Memory related tasks were not affected 10 min after ending sedation. Cognitive impairment in attention and psychomotor function after propofol and remifentanil sedation was significant and large and could be easily detected by computerized cognitive tests. Even though, patients were fully recovered 40 min after ending the procedure. From a cognitive recovery point of view, larger studies should be undertaken to propose adequate criteria for discharge

The RESPITE trial: remifentanil intravenously administered patient-controlled analgesia (PCA) versus pethidine intramuscular injection for pain relief in labour: study protocol for a randomised controlled trial.

Science.gov (United States)

Wilson, Matthew; MacArthur, Christine; Gao Smith, Fang; Homer, Leanne; Handley, Kelly; Daniels, Jane

2016-12-12

The commonest opioid used for pain relief in labour is pethidine (meperidine); however, its effectiveness has long been challenged and the drug has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. Over a third of women receiving pethidine require an epidural due to inadequate pain relief. Epidural analgesia increases the risk of an instrumental vaginal delivery and its associated effects. Therefore, there is a clear need for a safe, effective, alternative analgesic to pethidine. Evidence suggests that remifentanil patient-controlled analgesia (PCA) reduces epidural conversion rates compared to pethidine; however, no trial has yet investigated this as a primary endpoint. We are, therefore, comparing pethidine intramuscular injection to remifentanil PCA in a randomised controlled trial. Women in established labour, requesting systemic opioid pain relief, will be randomised to either intravenously administered remifentanil PCA (intervention) or pethidine intramuscular injection (control) in an unblinded, 1:1 individual randomised trial. Following informed consent, 400 women in established labour, who request systemic opioid pain relief, from NHS Trusts across England will undergo a minimised randomisation by a computer or automated telephone system to either pethidine or remifentanil. In order to balance the groups this minimisation is based on four parameters; parity (nulliparous versus multiparous), maternal age (Asian (Pakistani/Indian/Bangladeshi) versus Other) and induced versus spontaneous labour. The effectiveness of pain relief provided by each technique will be recorded every 30 min after time zero, until epidural placement, delivery or transfer to theatre, quantified by Visual Analogue Scale. Incidence of maternal side effects including sedation, delivery mode, foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breastfeeding within the first hour of birth

[Stress-induced hyperalgesia (SIH) as a consequence of emotional deprivation and psychosocial traumatization in childhood : Implications for the treatment of chronic pain].

Science.gov (United States)

Egle, U T; Egloff, N; von Känel, R

2016-12-01

It is now widely recognized that in many chronic pain syndromes the intensity and severity of individually perceived pain does not correlate consistently with the degree of peripheral nervous system tissue damage or with the intensity of primary afferent or spinal nociceptive neurone activity. In particular, stress and anxiety exert modulatory influences on pain depending on the nature, duration and intensity of the stressor and developmental influences on the maturation of the stress as well as the pain system. In some chronic pain syndromes, e. g. fibromyalgia, TMD or somatoform disorders, no nociceptive or neuropathic input is detectable. We summarise the studies investigating the neural substrates and neurobiological mechanisms of stress-induced hyperalgesia (SIH) in animals and humans. The review provides new perspectives and challenges for the current and future treatment of chronic pain.

Intradermal administration of magnesium sulphate and magnesium chloride produces hypesthesia to mechanical but hyperalgesia to heat stimuli in humans

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Ikemoto Tatsunori

2009-08-01

Full Text Available Abstract Background Although magnesium ions (Mg2+ are known to display many similar features to other 2+ charged cations, they seem to have quite an important and unique role in biological settings, such as NMDA blocking effect. However, the role of Mg2+ in the neural transmission system has not been studied as sufficiently as calcium ions (Ca2+. To clarify the sensory effects of Mg2+ in peripheral nervous systems, sensory changes after intradermal injection of Mg2+ were studied in humans. Methods Magnesium sulphate, magnesium chloride and saline were injected into the skin of the anterior region of forearms in healthy volunteers and injection-induced irritating pain ("irritating pain", for short, tactile sensation, tactile pressure thresholds, pinch-pain changes and intolerable heat pain thresholds of the lesion were monitored. Results Flare formation was observed immediately after magnesium sulphate or magnesium chloride injection. We found that intradermal injections of magnesium sulphate and magnesium chloride transiently caused irritating pain, hypesthesia to noxious and innocuous mechanical stimulations, whereas secondary hyperalgesia due to mechanical stimuli was not observed. In contrast to mechanical stimuli, intolerable heat pain-evoking temperature was significantly decreased at the injection site. In addition to these results, spontaneous pain was immediately attenuated by local cooling. Conclusion Membrane-stabilizing effect and peripheral NMDA-blocking effect possibly produced magnesium-induced mechanical hypesthesia, and extracellular cation-induced sensitization of TRPV1 channels was thought to be the primary mechanism of magnesium-induced heat hyperalgesia.

Secondary hyperalgesia phenotypes exhibit differences in brain activation during noxious stimulation

DEFF Research Database (Denmark)

Asghar, Mohammad Sohail; Pereira, Manuel Pedro; Werner, Mads Utke

2015-01-01

of the burn-injury) (p right (p = 0.001) and left caudate nucleus (p = 0.01) was detected....... To study differences in the propensity to develop central sensitization we examined differences in brain activity and anatomy according to individual phenotypical expression of secondary hyperalgesia by magnetic resonance imaging. Forty healthy volunteers received a first-degree burn-injury (47 °C, 7 min......, 9 cm(2)) on the non-dominant lower-leg. Areas of secondary hyperalgesia were assessed 100 min after the injury. We measured neuronal activation by recording blood-oxygen-level-dependent-signals (BOLD-signals) during mechanical noxious stimulation before burn injury and in both primary and secondary...

Rikkunshito prevents paclitaxel-induced peripheral neuropathy through the suppression of the nuclear factor kappa B (NFκB phosphorylation in spinal cord of mice.

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Junzo Kamei

Full Text Available Peripheral neuropathy is the major side effect caused by paclitaxel, a microtubule-binding antineoplastic drug. Paclitaxel-induced peripheral neuropathy causes a long-term negative impact on the patient's quality of life. However, the mechanism underlying paclitaxel-induced peripheral neuropathy is still unknown, and there is no established treatment. Ghrelin is known to attenuate thermal hyperalgesia and mechanical allodynia in chronic constriction injury of the sciatic nerve, and inhibit the activation of nuclear factor kappa B (NFκB in the spinal dorsal horn. Rikkunshito (RKT, a kampo medicine, increases the secretion of ghrelin in rodents and humans. Thus, RKT may attenuate paclitaxel-induced peripheral neuropathy by inhibiting phosphorylated NFκB (pNFκB in the spinal cord. We found that paclitaxel dose-dependently induced mechanical hyperalgesia in mice. Paclitaxel increased the protein levels of spinal pNFκB, but not those of spinal NFκB. NFκB inhibitor attenuated paclitaxel-induced mechanical hyperalgesia suggesting that the activation of NFκB mediates paclitaxel-induced hyperalgesia. RKT dose-dependently attenuated paclitaxel-induced mechanical hyperalgesia. Ghrelin receptor antagonist reversed the RKT-induced attenuation of paclitaxel-induced mechanical hyperalgesia. RKT inhibited the paclitaxel-induced increase in the protein levels of spinal pNFκB. Taken together, the present study indicates that RKT exerts an antihyperalgesic effect in paclitaxel-induced neuropathic pain by suppressing the activation of spinal NFκB.

Remifentanil analgesia during external cephalic version for breech presentation in nulliparous women at term: A randomized controlled trial.

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Wang, Zhi-Hong; Yang, Yi; Xu, Gui-Ping

2017-03-01

The aim of the study was to assess the efficacy and safety of remifentanil for pain relief during external cephalic version (ECV) for breech presentation in nulliparous women at term. A total of 144 nulliparous women with singleton breech presentation were randomly divided into the intervention group and the placebo group, with 72 subjects in each group. The subjects in the intervention group received remifentanil (infused at 0.1 μg kg min with demand boluses of 0.1 μg/kg), whereas those in the placebo group were given saline placebo. This study was conducted from May 2013 to April 2016. The outcomes measures include pain (measured with the visual analog scale, VAS), success rate of ECV, maternal satisfaction for ECV, and adverse events. A total of 137 participants completed the study. The intervention with remifentanil showed greater efficacy than did placebo in decreasing the VAS score immediately after ECV (intervention group 4.3 ± 2.2 vs placebo group 6.4 ± 2.5, P < 0.01). A significant difference in the ECV success rate was also found between the 2 groups (intervention group 56.9% vs placebo group 38.9%, P = 0.03). In addition, a significant difference in the satisfaction score was also detected (intervention group 9.3 ± 0.9 vs placebo group 6.7 ± 1.2, P < 0.01). The observed adverse events were similar between the 2 groups. This study shows that remifentanil could decrease pain, improve the ECV success rate, and improve satisfaction in nulliparous women at term during the period of ECV. Furthermore, it is also well tolerated with few adverse events.

Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

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Woolf Clifford J

2005-12-01

Full Text Available Abstract Background Pain is elicited by cold, and a major feature of many neuropathic pain states is that normally innocuous cool stimuli begin to produce pain (cold allodynia. To expand our understanding of cold induced pain states we have studied cold pain behaviors over a range of temperatures in several animal models of chronic pain. Results We demonstrate that a Peltier-cooled cold plate with ± 1°C sensitivity enables quantitative measurement of a detection withdrawal response to cold stimuli in unrestrained rats. In naïve rats the threshold for eliciting cold pain behavior is 5°C. The withdrawal threshold for cold allodynia is 15°C in both the spared nerve injury and spinal nerve ligation models of neuropathic pain. Cold hyperalgesia is present in the spared nerve injury model animals, manifesting as a reduced latency of withdrawal response threshold at temperatures that elicit cold pain in naïve rats. We also show that following the peripheral inflammation produced by intraplantar injection of complete Freund's adjuvant, a hypersensitivity to cold occurs. Conclusion The peltier-cooled provides an effective means of assaying cold sensitivity in unrestrained rats. Behavioral testing of cold allodynia, hyperalgesia and pain will greatly facilitate the study of the neurobiological mechanisms involved in cold/cool sensations and enable measurement of the efficacy of pharmacological treatments to reduce these symptoms.

The effect of propofol-remifentanil anesthesia on selected seizure quality indices in electroconvulsive therapy.

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Dinwiddie, Stephen H; Glick, David B; Goldman, Morris B

2012-07-01

Use of a short-acting opiate to potentiate anesthetic induction agents has been shown to increase seizure duration in electroconvulsive therapy (ECT), but little is known of the effect of this combination on indices of seizure quality. To determine whether anesthetic modality affects commonly provided indices of seizure quality. Twenty-five subjects were given propofol 2 mg/kg body weight for their first ECT session, at which time seizure threshold was titrated. Subjects thereafter alternated between that anesthetic regimen or propofol 0.5 mg/kg plus remifentanil 1 mcg/kg. Linear mixed models with random subject effect, adjusting for electrode placement, electrical charge, and number of treatments, were fit to estimate effect of anesthesia on seizure duration and several standard seizure quality indices (average seizure energy, time to peak electroencephalography (EEG) power, maximum sustained power, interhemispheric coherence, early and midictal EEG amplitude, and maximum sustained interhemispheric EEG coherence). Propofol-remifentanil anesthesia significantly lengthened seizure duration and was associated with longer time to reach maximal EEG power and coherence as well as maximal degree of interhemispheric EEG coherence. No effect was seen on early ictal amplitude or average seizure energy index. Propofol-remifentanil anesthesia prolongs seizure duration and has a significant effect on some, but not all, measures of seizure quality. This effect may be of some benefit in cases where adequate seizures are otherwise difficult to elicit. Varying anesthetic technique may allow more precise investigation of the relationships between and relative impacts of commonly used seizure quality indices on clinical outcomes and ECT-related cognitive side effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Enhanced brain responses to C-fiber input in the area of secondary hyperalgesia induced by high-frequency electrical stimulation of the skin.

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van den Broeke, Emanuel N; Mouraux, André

2014-11-01

High-frequency electrical stimulation (HFS) of the human skin induces an increase in both mechanical and heat pain sensitivity in the surrounding unconditioned skin. The aim of this study was to investigate the effect of HFS on the intensity of perception and brain responses elicited by the selective activation of C fibers. HFS was applied to the ventral forearm of 15 healthy volunteers. Temperature-controlled CO2 laser stimulation was used to activate selectively low-threshold C-fiber afferents without concomitantly activating Aδ-fiber afferents. These stimuli were detected with reaction times compatible with the conduction velocity of C fibers. The intensity of perception and event-related brain potentials (ERPs) elicited by thermal stimuli delivered to the surrounding unconditioned skin were recorded before (T0) and after HFS (T1: 20 min after HFS; T2: 45 min after HFS). The contralateral forearm served as a control. Mechanical hyperalgesia following HFS was confirmed by measuring the change in the intensity of perception elicited by mechanical punctate stimuli. HFS resulted in increased intensity of perception to mechanical punctate stimulation and selective C-fiber thermal stimulation at both time points. In contrast, the N2 wave of the ERP elicited by C-fiber stimulation (679 ± 88 ms; means ± SD) was enhanced at T1 but not at T2. The P2 wave (808 ± 105 ms) was unaffected by HFS. Our results suggest that HFS enhances the sensitivity to thermal C-fiber input in the area of secondary hyperalgesia. However, there was no significant enhancement of the magnitude of the C-fiber ERPs at T2, suggesting that quickly adapting C fibers do not contribute to this enhancement. Copyright © 2014 the American Physiological Society.

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

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Eiji Masaki

2016-03-01

Full Text Available Background: Brain-derived neurotrophic factor (BDNF from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Results: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. Conclusion: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials

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Carstensen, M; Møller, A M

2010-01-01

In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient......-controlled analgesia (PCA) for postoperative pain in order to clarify this controversy. Our primary aim was to compare the effectiveness and safety of postoperative administered ketamine in addition to opioid for i.v. PCA compared with i.v. PCA with opioid alone. Studies were identified from the Cochrane Library 2003...... of 4.5. Pain was assessed using visual analogue scales or verbal rating scales. Six studies showed significant improved postoperative analgesia with the addition of ketamine to opioids. Five studies showed no significant clinical improvement. For thoracic surgery, the addition of ketamine to opioid...

S-ketamine modulates hyperalgesia in patients with chronic pancreatitis pain

NARCIS (Netherlands)

Bouwense, S.A.W.; Buscher, H.C.J.L.; Goor, H. van; Wilder-Smith, O.H.G.

2011-01-01

BACKGROUND AND OBJECTIVES: Upper abdominal pain is a dominant feature of chronic pancreatitis. A key phenomenon in this context is hyperalgesia, typically associated with N-methyl-d-aspartate receptor activation. This exploratory study evaluates acute effects of S-ketamine, a noncompetitive

Total intravenous anesthesia using remifentanil in extracorporeal shock wave lithotripsy (ESWL). Comparison of two dosages: a randomized clinical trial.

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Cannata, F; Spinoglio, A; Di Marco, P; Luzi, M; Canneti, A; Ricciuti, G; Reale, C

2014-01-01

Extracorporeal Shock Wave Lithotripsy is usually performed in day surgery setting, consequently people who undergo to this procedure need a safe and fast recovery. Conscious sedation with remifentanil can relieve from pain and keep patients in touch with anaesthesiologists. Few publications tell about infusion rates administered to perform this procedure7. The aim of this study is to assess which is the most appropriate infusion rate. Patients were randomly assigned to two groups. Two different infusion rates were compared: 0,05 mcg/kg/min, GROUP A (N.=114), vs. 0.1 µg/kg/min, GROUP B (N.=114). Patients' vital signs, additional analgesic requests, PONV (postoperative nausea and vomiting) and other side effects were registered. The deepness of sedation and patient's satisfaction were evaluated referring to Obsever's Assessment of Alertness and Sedation scale (O/ASS) and using a Likert's scale respectively. Pain intensity was assessed with a 11-points VAS (visual analogue scale). Differences between groups were analyzed using Student t test for independent variables. The χ2 test was used to analyze categorical variables. The study enrolled 228 patients and assigned them to two groups (N.=114). No significant differences were found regarding Likert's scale values (P=0.20), additional analgesic request (P=0.30) and mean VAS values (P>0.05) between the two groups. The difference between the two groups about PONV, hypotension, oxygen desaturation and respiratory depression was statistically significant (P<0.05), as a matter of fact in group A these side effects occurred less frequently. The fifth degree of O/ASS was estimated in about 1.61±0.19 min and 2.987±0.20 min in group A and in group B respectively (P<0.05). According with previous results remifentanil at the infusion rate of 0.05 µg/kg/min provides an effective analgesia, causing a lower incidence of side effect than 0.1 µg/kg/min, granting a fast and safe recovery.

Imatinib-induced postoperative periorbital purpura: GASP (Gleevec-Associated Surgical Purpura) in a woman with imatinib-treated chronic myelogenous leukemia.

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Anzalone, C Lane; Cohen, Philip R; Kurzrock, Razelle; Cortes, Jorge E

2014-01-15

Imatinib mesylate is a selective tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukemia. Ocular side effects of imatinib include periorbital edema, which may become so severe as to obstruct the visual field. The purpose of this case study is to describe the clinical characteristics of imatinib- induced postoperative periorbital purpura. We retrospectively reviewed the medical literature using PubMed, searching the terms edema, Gleevec, imatinib, periorbital, postoperative and purpura. Patient reports and previous reviews of the subject were critically assessed and the salient features are presented. Three patients have undergone surgery to reduce the imatinib-induced periorbital edema; two of these individuals have developed imatinib-induced postoperative periorbital purpura. We recommend discontinuing imatinib usage one week prior to periorbital surgery and not resuming therapy until the eighth postoperative day.

Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia

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Khodayari-Rostamabad, Ahmad; Olesen, Søren S; Graversen, Carina

2015-01-01

-theoretical measures and experimental pain tests were seen. CONCLUSIONS:: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative...

Generalized Hyperalgesia in Children and Adults Diagnosed With Hypermobility Syndrome and Ehlers-Danlos Syndrome Hypermobility Type: A Discriminative Analysis.

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Scheper, M C; Pacey, V; Rombaut, L; Adams, R D; Tofts, L; Calders, P; Nicholson, L L; Engelbert, R H H

2017-03-01

Lowered pressure-pain thresholds have been demonstrated in adults with Ehlers-Danlos syndrome hypermobility type (EDS-HT), but whether these findings are also present in children is unclear. Therefore, the objectives of the study were to determine whether generalized hyperalgesia is present in children with hypermobility syndrome (HMS)/EDS-HT, explore potential differences in pressure-pain thresholds between children and adults with HMS/EDS-HT, and determine the discriminative value of generalized hyperalgesia. Patients were classified in 1 of 3 groups: HMS/EDS-HT, hypermobile (Beighton score ≥4 of 9), and healthy controls. Descriptive data of age, sex, body mass index, Beighton score, skin laxity, and medication usage were collected. Generalized hyperalgesia was quantified by the average pressure-pain thresholds collected from 12 locations. Confounders collected were pain locations/intensity, fatigue, and psychological distress. Comparisons between children with HMS/EDS-HT and normative values, between children and adults with HMS/EDS-HT, and corrected confounders were analyzed with multivariate analysis of covariance. The discriminative value of generalized hyperalgesia employed to differentiate between HMS/EDS-HT, hypermobility, and controls was quantified with logistic regression. Significantly lower pressure-pain thresholds were found in children with HMS/EDS-HT compared to normative values (range -22.0% to -59.0%; P ≤ 0.05). When applying a threshold of 30.8 N/cm 2 for males and 29.0 N/cm 2 for females, the presence of generalized hyperalgesia discriminated between individuals with HMS/EDS-HT, hypermobility, and healthy controls (odds ratio 6.0). Children and adults with HMS/EDS-HT are characterized by hypermobility, chronic pain, and generalized hyperalgesia. The presence of generalized hyperalgesia may indicate involvement of the central nervous system in the development of chronic pain. © 2016, American College of Rheumatology.

Subjects with Knee Osteoarthritis Exhibit Widespread Hyperalgesia to Pressure and Cold.

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Penny Moss

Full Text Available Hyperalgesia to mechanical and thermal stimuli are characteristics of a range of disorders such as tennis elbow, whiplash and fibromyalgia. This study evaluated the presence of local and widespread mechanical and thermal hyperalgesia in individuals with knee osteoarthritis, compared to healthy control subjects. Twenty-three subjects with knee osteoarthritis and 23 healthy controls, matched for age, gender and body mass index, were recruited for the study. Volunteers with any additional chronic pain conditions were excluded. Pain thresholds to pressure, cold and heat were tested at the knee, ipsilateral heel and ipsilateral elbow, in randomized order, using standardised methodology. Significant between-groups differences for pressure pain and cold pain thresholds were found with osteoarthritic subjects demonstrating significantly increased sensitivity to both pressure (p = .018 and cold (p = .003 stimuli, compared with controls. A similar pattern of results extended to the pain-free ipsilateral ankle and elbow indicating widespread pressure and cold hyperalgesia. No significant differences were found between groups for heat pain threshold, although correlations showed that subjects with greater sensitivity to pressure pain were also likely to be more sensitive to both cold pain and heat pain. This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may play a role in ongoing arthritic pain for some patients.

Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation.

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Sharma, Neelam; Arora, Sandeep; Madan, Jitender

2018-02-01

Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

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Sluka, K A; Wright, A

2001-01-01

Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.

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Rui-Yun Bi

Full Text Available Temporomandibular disorders (TMDs have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7 plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ. Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored.Estrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ, the G protein coupled estrogen receptor (GPR30, and Nav1.7 in TG were examined using immunohistofluorescence.Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

NARCIS (Netherlands)

The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

2008-01-01

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

NARCIS (Netherlands)

The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

Cold Pain Threshold Identifies a Subgroup of Individuals With Knee Osteoarthritis That Present With Multimodality Hyperalgesia and Elevated Pain Levels.

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Wright, Anthony; Benson, Heather A E; Will, Rob; Moss, Penny

2017-09-01

Cold hyperalgesia has been established as an important marker of pain severity in a number of conditions. This study aimed to establish the extent to which patients with knee osteoarthritis (OA) demonstrate widespread cold, heat, and pressure hyperalgesia. OA participants with widespread cold hyperalgesia were compared with the remaining OA cohort to determine whether they could be distinguished in terms of hyperalgesia, pain report, pain quality, and physical function. A total of 80 participants with knee OA and 40 matched healthy, pain-free controls participated. OA participants completed a washout of their usual medication. Quantitative sensory testing was completed at 3 sites using standard methods. Cold pain threshold (CPT) and heat pain thresholds (HPT) were tested using a Peltier thermode and pressure pain thresholds (PPT) using a digital algometer. All participants completed the short-form health survey questionnaire and OA participants completed the PainDETECT, Western Ontario and McMaster Universities Osteoarthritis Index of the Knee (WOMAC), and pain quality assessment scale questionnaires. OA participants demonstrated widespread cold hyperalgesia (Ppain, decreased function, and more features of neuropathic pain. This study identified a specific subgroup of patients with knee OA who exhibited widespread, multimodality hyperalgesia, more pain, more features of neuropathic pain, and greater functional impairment. Identification of patients with this pain phenotype may permit more targeted and effective pain management.

The influence of norepinephrine and phenylephrine on cerebral perfusion and oxygenation during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia in piglets

DEFF Research Database (Denmark)

Mikkelsen, Mai Louise Grandsgaard; Ambrus, Rikard; Rasmussen, Rune

2018-01-01

of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation). Results During propofol......–remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0......–remifentanil–dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group. Conclusions Cerebral partial pressure of oxygen measured by Licox...

Exploring the potential effect of Ocimum sanctum in vincristine-induced neuropathic pain in rats

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Jaggi Amteshwar

2010-01-01

Full Text Available Abstract The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p. for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.

[The Influence of Flurbiprofen on the Frequency of Postoperative Shivering].

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Urabe, Tomoaki; Nakanuno, Ryuichi; Hayase, Kazuma; Takata, Nanako; Senami, Masaki

2015-10-01

Many methods to prevent postoperative shivering (POS) has been reported. However, there are few reports demonstrating the effect of flurbiprofen on POS which affects the set point in the thermocenter of the hypothalamus. One hundred and forty six patients undergoing lung lobectomy or segmentectomy under video-assisted thoracic surgery were divided into a flurbiprofen-treated group (Group F) and a non-treated group (Group N). We retrospectively investigated the incidence of POS associated with total intravenous anesthesia with epidural anesthesia compared with or without flurbiprofen. We weighed the incidence of POS against age, body mass index, the effective site concentration of fentanyl on extubation, the mean dose of remifentanil, the minimum rectal temperature, the surgical duration and total hemorrhage volume based on the anesthetic chart Chi-square and Student t-test were used for statistical analysis. Although the surgical duration in Group F was shorter than that in Group N (223±83 vs. 165±80 (min), Pflurbiprofen has a possible beneficial effect in preventing POS.

Inguinal hernia repair in day surgery: the role of MAC (Monitored Anesthesia Care) with remifentanil

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USAI, S.; AMATUCCI, C.; PEROTTI, B.; RUGGERI, L.; ILLUMINATI, G.; TELLAN, G.

2017-01-01

Background The extension of indications for procedures in a Day Surgery (DS) setting has led to changes in the anesthetic and surgical treatment of Inguinal Hernias (IH). According to the recommendations of the European Hernia Society, the treatment of IH in DS units should be performed under Monitored Anesthesia Care (MAC). Patients and methods 960 patients underwent IH repairs over a period of 24 months. The patients were randomly divided into two groups: R (remifentanil) and F (fentanyl); the group F was considered as a control group. The exclusion criteria in both group were: morbid obesity (BMI>40 or BMI>35 in association with high blood pressure or diabetes); coagulopathy; OSAS (obstructive sleep apnea syndrome) with AHI >10; cardiovascular, respiratory, renal, hepatic or metabolic disease; history of substances abuse; GERD-related esophagitis (gastro-esophageal reflux disease); chronic analgesic use; allergy to local anesthetic and ASA>III. Patients reported their level of pain on a verbal numeric scale (VNS), with scores ranging from 0 to 10. For each patient systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation (SpO2) were recorded. The results are presented as the mean value ± standard deviations; statistical analysis was performed using Student’s t-test. Results Amongst the 960 procedures, complications or side effects related to the anesthetic techniques didn’t occur; no procedure-related complications requiring mechanical ventilation support were reported. Our research focused on evaluating remifentanil effectiveness in pain control and its impact on hemodynamic stability and respiratory function. There was a significant difference between the two groups with regard to the VNS. Conclusions Remifentanil, is an excellent drug for pain control during intra-operative procedures, that allows an optimal hemodynamic stability for IH repairs in a DS setting, due to its

Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

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GURPREET KAUR

2015-03-01

Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome

International Nuclear Information System (INIS)

Heymann, Steve; Bourgier, Céline; Delaloge, Suzette; Rahal, Arslane; Caron, Olivier; Frebourg, Thierry; Barreau, Lise; Pachet, Corinne; Mathieu, Marie-Christine; Marsiglia, Hugo

2010-01-01

There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies. We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies. Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy. These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy

Bromodomain-containing Protein 4 Activates Voltage-gated Sodium Channel 1.7 Transcription in Dorsal Root Ganglia Neurons to Mediate Thermal Hyperalgesia in Rats.

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Hsieh, Ming-Chun; Ho, Yu-Cheng; Lai, Cheng-Yuan; Wang, Hsueh-Hsiao; Lee, An-Sheng; Cheng, Jen-Kun; Chau, Yat-Pang; Peng, Hsien-Yu

2017-11-01

Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. Male Sprague-Dawley rats received hind paw injections of complete Freund's adjuvant to induce hyperalgesia. The dorsal root ganglia were examined to detect changes in bromodomain-containing protein 4 expression and the activation of genes involved in the expression of voltage-gated sodium channel 1.7, which is a key pain-related ion channel. The intraplantar complete Freund's adjuvant injections resulted in thermal hyperalgesia (4.0 ± 1.5 s; n = 7). The immunohistochemistry and immunoblotting results demonstrated an increase in the bromodomain-containing protein 4-expressing dorsal root ganglia neurons (3.78 ± 0.38 fold; n = 7) and bromodomain-containing protein 4 protein levels (2.62 ± 0.39 fold; n = 6). After the complete Freund's adjuvant injection, histone H3 protein acetylation was enhanced in the voltage-gated sodium channel 1.7 promoter, and cyclin-dependent kinase 9 and phosphorylation of RNA polymerase II were recruited to this area. Furthermore, the voltage-gated sodium channel 1.7-mediated currents were enhanced in neurons of the complete Freund's adjuvant rats (55 ± 11 vs. 19 ± 9 pA/pF; n = 4 to 6 neurons). Using bromodomain-containing protein 4-targeted antisense small interfering RNA to the complete Freund's adjuvant-treated rats, the authors demonstrated a reduction in the expression of bromodomain-containing protein 4 (0.68 ± 0.16 fold; n = 7), a reduction in thermal hyperalgesia (7.5 ± 1.5 s; n = 7), and a reduction in the increased voltage-gated sodium channel 1.7 currents (21 ± 4 pA/pF; n = 4 to 6 neurons). Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is

Short-term pre- and post-operative stress prolongs incision-induced pain hypersensitivity without changing basal pain perception.

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Cao, Jing; Wang, Po-Kai; Tiwari, Vinod; Liang, Lingli; Lutz, Brianna Marie; Shieh, Kun-Ruey; Zang, Wei-Dong; Kaufman, Andrew G; Bekker, Alex; Gao, Xiao-Qun; Tao, Yuan-Xiang

2015-12-02

Chronic stress has been reported to increase basal pain sensitivity and/or exacerbate existing persistent pain. However, most surgical patients have normal physiological and psychological health status such as normal pain perception before surgery although they do experience short-term stress during pre- and post-operative periods. Whether or not this short-term stress affects persistent postsurgical pain is unclear. In this study, we showed that pre- or post-surgical exposure to immobilization 6 h daily for three consecutive days did not change basal responses to mechanical, thermal, or cold stimuli or peak levels of incision-induced hypersensitivity to these stimuli; however, immobilization did prolong the duration of incision-induced hypersensitivity in both male and female rats. These phenomena were also observed in post-surgical exposure to forced swimming 25 min daily for 3 consecutive days. Short-term stress induced by immobilization was demonstrated by an elevation in the level of serum corticosterone, an increase in swim immobility, and a decrease in sucrose consumption. Blocking this short-term stress via intrathecal administration of a selective glucocorticoid receptor antagonist, RU38486, or bilateral adrenalectomy significantly attenuated the prolongation of incision-induced hypersensitivity to mechanical, thermal, and cold stimuli. Our results indicate that short-term stress during the pre- or post-operative period delays postoperative pain recovery although it does not affect basal pain perception. Prevention of short-term stress may facilitate patients' recovery from postoperative pain.

Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia

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Kobayashi Kimiko

2008-04-01

Full Text Available Abstract Background Honeybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK in the generation of BV-induced pain hypersensitivity. Results We found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38 was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn. Conclusion The results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.

Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

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Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

2015-01-01

The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was αpain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Trigeminal purinergic P2X4 receptor involved in experimental occlusal interference-induced hyperalgesia in rat masseter muscle].

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Xu, Xiaoxiang; Cao, Ye; Ding, Tingting; Fu, Kaiyuan; Xie, Qiufei

2016-03-01

To explore the expression of purinergic p2X4 receptor (P2X4R) in trigeminal ganglion of rats after occlusal interference. Investigation of peripheral receptor mechanism of occlusal interference-induced masticatory muscle pain will aid the development of drug intervention against this condition. Experimental occlusal interference was established by application of 0.4 mm metal crown to the upper right first molar of male Sprague-Dawley rats. Real-time PCR assay was used to investigate P2X4R mRNA level in trigeminal ganglion in rats with occlusal interference for 3, 7, 10 and 14 days and in control rats without occlusal interference (n=5 in each). Retrograde labelling combining immunofluorescence was performed to evaluate the percentage of P2X4R-positive cells in masseter afferent neurons (n=5 in each group). Graded concentrations of P2XR antagonist TNP-ATP (0.1, 10, 125, 250, 500 μmol/L) or saline (n=5 in each group) was administrated in right masseter and the mechanical sensitivity of bilateral masseters was measured before occlusal interference application, before the injection, and 30 min as well as 60 min after the injection. Compared with control rats (P2X4R mRNA: right side: 1.00±0.26, left side: 0.94± 0.21; percentage of P2X4R-positive masseter afferents: right side: [64.3±6.3]%, left side: [67.7±5.8]%), the level of P2X4R mRNA in bilateral trigeminal ganglia (right side: 5.98±3.56; left side: 5.06±2.88) of rats with occlusal interference for 7 days up-regulated (Pocclusal interference-induced masseter hyperalgesia.

Target-controlled infusion of remifentanil with or without flurbiprofen axetil in sedation for extracorporeal shock wave lithotripsy of pancreatic stones: a prospective, open-label, randomized controlled trial.

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Yang, Yu-Guang; Hu, Liang-Hao; Chen, Hui; Li, Bo; Fan, Xiao-Hua; Li, Jin-Bao; Wang, Jia-Feng; Deng, Xiao-Ming

2015-11-07

Extracorporeal shock wave lithotripsy (ESWL) is an effective therapeutic method used to treat patients with pancreatic stones. However, the anesthesia for this procedure has been underappreciated, with minimal reports of these procedures in certain case series with general or epidural anesthesia. A cohort of 60 patients who elected to undergo ESWL in order to treat pancreatic stones for the first time were randomly selected and divided into two groups. One group of patients received target controlled infusion (TCI) of remifentanil, while the other group of patients received TCI of remifentanil plus a bolus of flurbiprofen axetil (a cyclooxygenase inhibitor) (Rem group and Rem + Flu group, n = 30 for each group). The Dixon's up-and-down method was used to calculate the half maximum effective concentration (EC50) of remifentanil. Visual analogue scales of pain, Ramsay sedation scale, hemodynamic changes, and adverse events were also recorded. The EC50 of remifentanil was calculated to be 4.0 ng/ml (95 % confidential interval: 3.84 ng/ml, 4.16 ng/ml) and 2.76 ng/ml (95 % confidential interval: 2.63 ng/ml, 2.89 ng/ml) in the Rem group and Rem + Flu group respectively (p flurbiprofen axetil provided satisfactory analgesia and sedation for ESWL of pancreatic stones with less adverse events. (Clinicaltrial.gov: NCT01998217 ; registered on November 19, 2013).

Capsaicin-induced neurogenic inflammation in pig skin: A behavioural study

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di Giminiani, Pierpaolo; Petersen, Lars Jelstrup; Herskin, Mette S

2014-01-01

Topical capsaicin is a well-established model of experimental hyperalgesia. Its application to the study of animals has been limited to few species. The effect of topical capsaicin on hyperalgesia in porcine skin was evaluated as part of a study of inflammatory pain in the pig. Two experiments were...... carried out on pigs of 27 ± 5 kg (n = 8) and 57 ± 3 kg (n = 16). Thermal and mechanical noxious stimuli were provided (CO2 laser and Pressure Application Measurement device) to assess avoidance behaviours. Capsaicin induced significant thermal hyperalgesia in the smaller pigs (P

Transcutaneous electrical nerve stimulation on Yongquan acupoint reduces CFA-induced thermal hyperalgesia of rats via down-regulation of ERK2 phosphorylation and c-Fos expression.

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Yang, Lin; Yang, Lianxue; Gao, Xiulai

2010-07-01

Activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and its involvement in regulating gene expression in spinal dorsal horn, cortical and subcortical neurons by peripheral noxious stimulation contribute to pain hypersensitivity. Transcutaneous electrical nerve stimulation (TENS) is a treatment used in physiotherapy practice to promote analgesia in acute and chronic inflammatory conditions. In this study, a total number of 114 rats were used for three experiments. Effects of complete Freund's adjuvant (CFA)-induced inflammatory pain hypersensitivity and TENS analgesia on ERK1/2 phosphorylation and c-Fos protein expression were examined by using behavioral test, Western blot, and immunostaining methods. We found that CFA injection caused an area of localized swelling, erythema, hypersensitivity to thermal stimuli, the decreased response time of hind paw licking (HPL), as well as upregulation of c-Fos protein expression and ERK2 phosphorylation in the ipsilateral spinal dorsal horn and the contralateral primary somatosensory area of cortex and the amygdala of rats. TENS on Yongquan acupoint for 20 min produced obvious analgesic effects as demonstrated with increased HPL to thermal stimuli of CFA-treated rats. In addition, TENS application suppressed the CFA-induced ERK2 activation and c-Fos protein expression. These results suggest that down-regulation of ERK2 phosphorylation and c-Fos expression were involved in TENS inhibition on CFA-induced thermal hyperalgesia of rats.

A novel and selective poly (ADP-ribose polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

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Lauren E Ta

Full Text Available Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose polymerase (PARP inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888 would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice.An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p. injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment.Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

A novel and selective poly (ADP-ribose) polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

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Ta, Lauren E; Schmelzer, James D; Bieber, Allan J; Loprinzi, Charles L; Sieck, Gary C; Brederson, Jill D; Low, Philip A; Windebank, Anthony J

2013-01-01

Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice. An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment. Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy.

Local cooling does not prevent hyperalgesia following burn injury in humans

DEFF Research Database (Denmark)

Werner, Mads U; Lassen, Birgit Vibeke; Pedersen, Juri L

2002-01-01

One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti-inflammato......One of the oldest methods of pain relief following a burn injury is local application of ice or cold water. Experimental data indicate that cooling may also reduce the severity of tissue injury and promote wound healing, but there are no controlled studies in humans evaluating the anti...... and mechanical detection thresholds, thermal and mechanical pain responses, area of secondary hyperalgesia), first degree burn injuries were induced on both calves by contact thermodes (12.5 cm(2), 47 degrees C for 7 min). Eight minutes after the burn injury, contact thermodes (12.5 cm(2)) were again applied...... on the burns. One of the thermodes cooled the burn (8 degrees C for 30 min) whereas the other thermode was a non-active dummy on the control burn. Inflammatory and sensory variables were followed for 160 min after end of the cooling procedure. The burn injury induced significant increases in skin temperature...

Effects of Daily Morphine Administration and Deprivation on Choice and Demand for Remifentanil and Cocaine in Rhesus Monkeys

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Wade-Galuska, Tammy; Galuska, Chad M.; Winger, Gail

2011-01-01

Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or…

Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy

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Liu Xian-Guo

2011-03-01

Full Text Available Abstract Long-term potentiation (LTP in nociceptive spinal pathways shares several features with hyperalgesia and has been proposed to be a cellular mechanism of pain amplification in acute and chronic pain states. Spinal LTP is typically induced by noxious input and has therefore been hypothesized to contribute to acute postoperative pain and to forms of chronic pain that develop from an initial painful event, peripheral inflammation or neuropathy. Under this assumption, preventing LTP induction may help to prevent the development of exaggerated postoperative pain and reversing established LTP may help to treat patients who have an LTP component to their chronic pain. Spinal LTP is also induced by abrupt opioid withdrawal, making it a possible mechanism of some forms of opioid-induced hyperalgesia. Here, we give an overview of targets for preventing LTP induction and modifying established LTP as identified in animal studies. We discuss which of the various symptoms of human experimental and clinical pain may be manifestations of spinal LTP, review the pharmacology of these possible human LTP manifestations and compare it to the pharmacology of spinal LTP in rodents.

Association of occlusal interference-induced masseter muscle hyperalgesia and P2X3 receptors in the trigeminal subnucleus caudalis and midbrain periaqueductal gray.

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Sun, Shuzhen; Qi, Dong; Yang, Yingying; Ji, Ping; Kong, Jingjing; Wu, Qingting

2016-03-02

P2X3 receptor plays a role in nociception transmission of orofacial pain in temporomandibular disorder patients. A previous study found that P2X3 receptors in masseter muscle afferent neurons and the trigeminal ganglia were involved in masseter muscle pain induced by inflammation caused by chemical agents or eccentric muscle contraction. In this study, we attempted to investigate changes in P2X3 receptors in the trigeminal subnucleus caudalis (Vc) and midbrain periaqueductal gray (PAG) in relation to the hyperalgesia of masseter muscles induced by occlusal interference. Experimental occlusal interference by crown application was established in 30 rats and another 30 rats were treated as sham controls. On days 1, 3, 7, 14, and 28 after crown application, the mechanical pain threshold was examined by von-Frey filaments. The expression of the P2X3 receptor in Vc and PAG was investigated by immunohistochemistry and quantitative PCR. We found that mechanical pain threshold of bilateral masseter muscles decreased significantly after occlusal interference, which remained for the entire experimental period. The mRNA expression of the P2X3 receptor increased significantly and the number of P2X3R-positive neurons increased markedly in Vc and PAG accordingly. These results indicate that the upregulated expression of P2X3 receptors in Vc and PAG may contribute toward the development of orofacial pain induced by occlusal interference and P2X3 receptors in the PAG may play a key role in the supraspinal antiociception effect.

The use of alfaxalone and remifentanil total intravenous anesthesia in a dog undergoing a craniectomy for tumor resection.

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Warne, Leon N; Beths, Thierry; Fogal, Sandra; Bauquier, Sébastien H

2014-11-01

A 7-year-old castrated border collie dog was anesthetised for surgical resection of a hippocampal mass. Anesthesia was maintained using a previously unreported TIVA protocol for craniectomy consisting of alfaxalone and remifentanil. Recovery was uneventful, and the patient was discharged from hospital. We describe the anesthetic management of this case.

Topical gabapentin gel alleviates allodynia and hyperalgesia in the chronic sciatic nerve constriction injury neuropathic pain model.

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Shahid, M; Subhan, F; Ahmad, N; Ali, G; Akbar, S; Fawad, K; Sewell, R D E

2017-04-01

Systemic gabapentin is a mainstay treatment for neuropathic pain though there are side-effects. Localized therapy may curtail such side-effects so a topical gabapentin dermal application was examined in the chronic constriction injury (CCI) model of neuropathic pain. Partial denervation CCI was achieved by rat sciatic nerve ligation. Gabapentin gel (10% w/w) was applied three times daily on the ipsilateral or contralateral plantar surface of the hind-paw, whereas in a concurrent systemic study, gabapentin was intraperitoneally administered daily (75 mg/kg) for 30 days. Tests for static- and dynamic-mechano-allodynia [paw withdrawal threshold (PWT) to von Frey filament application and latency (PWL) to light brushing], cold-allodynia [paw withdrawal duration (PWD) to acetone], heat- (PWL and PWD) and mechano-hyperalgesia (PWD to pin prick) were utilized to assess pain, whereas effects on locomotion (open field) and motor balance (rotarod and footprint analysis) were measured on days 5-30 post surgery. Topical application of gabapentin gel ipsilaterally but not contralaterally alleviated CCI-induced static- (days 10-30) and dynamic-allodynia (days 15-30), suppressed cold-allodynia (days 10-30), heat- (days 15-30) and mechano-hyperalgesia (days 5-30) indicating a local action. Systemic gabapentin exhibited similar pain profiles but was associated with motor impairment. The gabapentin gel formulation afforded desirable neuropathic pain alleviating effects devoid of unwanted systemic side-effects. These outcomes disclose an expedient pharmacological validation of the effectiveness of topical gabapentin gel against an extensive range of nociceptive stimulus modalities utilizing the CCI-induced neuropathic pain model. They also advocate further clinical studies on topical gabapentin with regard to certain neuropathic pain syndromes. Systemic gabapentin neuropathic pain management carries side-effects ostensibly preventable by localized therapy. This study validates the

The administration sequence of propofol and remifentanil does not affect the ED50 and ED95 of rocuronium in rapid sequence induction of anesthesia: a double-blind randomized controlled trial.

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Ozcelik, M; Guclu, C; Bermede, O; Baytas, V; Altay, N; Karahan, M A; Erdogan, B; Can, O

2016-04-01

The topic of drug administration sequence in rapid sequence induction (RSI) is still an object of interest in terms of rocuronium effectiveness. The aim of this prospective, randomized trial was to evaluate the effect of administration sequence of propofol and remifentanil on ED50 and ED95 of rocuronium in a RSI model. Eighty-four patients were randomized into Group Remifentanil (Group R, n = 43), where induction of general anesthesia started with remifentanil (2 µg/kg) and followed by propofol (2 mg/kg) and rocuronium administrations; and Group Propofol (Group P, n = 41), where induction of general anesthesia started with propofol and followed by remifentanil and rocuronium. First patients in each group were paralyzed by 0.8 mg/kg rocuronium. In case of acceptable intubation as evaluated according to the criteria described by Viby-Mogensen et al, rocuronium dose was decreased by 0.1 mg/kg for the next patient; otherwise, rocuronium dose was increased by 0.1 mg/kg. After three crossover points, increments or decrements in rocuronium dosage were set to 0.05 mg/kg. The process was repeated until a total of ten crossover points were obtained. The ED50 and ED95 doses of rocuronium were similar in Group R (0.182 mg/kg, and 0.244 mg/kg, respectively) and Group P (0.121 mg/kg, and 0.243 mg/kg, respectively) according to 95% CI of the estimates. There was no statistically significant difference in terms of clinically acceptable intubation conditions between the two groups (56.1% in Group R vs. 59% in Group P, p = 0.795). The choice of administration sequence of propofol and remifentanil does not have an impact on estimated ED50 and ED95 of rocuronium in providing acceptable intubation conditions in the RSI technique.

Mechanical nociception thresholds in lame sows: evidence of hyperalgesia as measured by two different methods.

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Nalon, E; Maes, D; Piepers, S; van Riet, M M J; Janssens, G P J; Millet, S; Tuyttens, F A M

2013-11-01

Lameness is a frequently occurring, painful condition of breeding sows that may result in hyperalgesia, i.e., an increased sensitivity to pain. In this study a mechanical nociception threshold (MT) test was used (1) to determine if hyperalgesia occurs in sows with naturally-occurring lameness; (2) to compare measurements obtained with a hand-held probe and a limb-mounted actuator connected to a digital algometer; and (3) to investigate the systematic left-to-right and cranial-to-caudal differences in MT. Twenty-eight pregnant sows were investigated, of which 14 were moderately lame and 14 were not lame. Over three testing sessions, repeated measurements were taken at 5 min intervals on the dorsal aspects of the metatarsi and metacarpi of all limbs. The MT was defined as the force in Newtons (N) that elicited an avoidance response, and this parameter was found to be lower in limbs affected by lameness than in normal limbs (Ptesting sessions (P<0.001), as well as between days (P<0.001). The findings provide evidence that lame sows experience hyperalgesia. Systematic differences between forelimb and hindlimb MT must be taken into account when such assessments are performed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pyrrolidine dithiocarbamate inhibits superoxide anion-induced pain and inflammation in the paw skin and spinal cord by targeting NF-κB and oxidative stress.

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Pinho-Ribeiro, Felipe A; Fattori, Victor; Zarpelon, Ana C; Borghi, Sergio M; Staurengo-Ferrari, Larissa; Carvalho, Thacyana T; Alves-Filho, Jose C; Cunha, Fernando Q; Cunha, Thiago M; Casagrande, Rubia; Verri, Waldiceu A

2016-06-01

We evaluated the effect of pyrrolidine dithiocarbamate (PDTC) in superoxide anion-induced inflammatory pain. Male Swiss mice were treated with PDTC and stimulated with an intraplantar or intraperitoneal injection of potassium superoxide, a superoxide anion donor. Subcutaneous PDTC treatment attenuated mechanical hyperalgesia, thermal hyperalgesia, paw oedema and leukocyte recruitment (neutrophils and macrophages). Intraplantar injection of superoxide anion activated NF-κB and increased cytokine production (IL-1β, TNF-α and IL-10) and oxidative stress (nitrite and lipid peroxidation levels) at the primary inflammatory foci and in the spinal cord (L4-L6). PDTC treatment inhibited superoxide anion-induced NF-κB activation, cytokine production and oxidative stress in the paw and spinal cord. Furthermore, intrathecal administration of PDTC successfully inhibited superoxide anion-induced mechanical hyperalgesia, thermal hyperalgesia and inflammatory response in peripheral foci (paw). These results suggest that peripheral stimulus with superoxide anion activates the local and spinal cord oxidative- and NF-κB-dependent inflammatory nociceptive mechanisms. PDTC targets these events, therefore, inhibiting superoxide anion-induced inflammatory pain in mice.

The effect of pre-emptive gabapentin on anaesthetic and analgesic requirements in patients undergoing rhinoplasty: A prospective randomised study

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Eman Ramadan Salama

2018-01-01

Full Text Available Background and Aims: Hypotensive anaesthesia is necessary in rhinoplasty for better visualisation of surgical field and reduction of surgery time. Gabapentin is a new generation anticonvulsant with anti-hyperalgesic and anti-nociceptive properties. We aimed to investigate the effect of pre-operative administration of oral gabapentin (1200 mg on anaesthetic requirements and post-operative analgesic consumption and its role in hypotensive anaesthesia for rhinoplasty. Methods: Seventy adult patients undergoing rhinoplasty, were randomly allocated to two groups. Group I (G I (n = 35 received gabapentin 1.2 g and Group II (G II (n = 35 received oral placebo capsules 2 h before surgery. General anaesthesia was maintained with sevoflurane in oxygen-nitrous oxide to maintain bispectral index value between 40 and 60, and remifentanil infusion to keep mean arterial pressure (MAP at 55–60 mmHg. End-tidal sevoflurane concentration, intra-operative remifentanil consumption and time to intended MAP were recorded. Visual analogue scale (VAS scores, post-operative analgesic requirements and side effects for the first 24 h were recorded. Results: G I required significantly lower intra-operative remifentanil (G I = 0.8 ± 0.26 mg and G II = 1.7 ± 0.42 mg; P = 0.001 and end-tidal sevoflurane concentration, with reduced doses of post-operative tramadol and diclofenac sodium. Time to the intended MAP was significantly less in G I than G II (59.1 ± 12.3 vs. 73.6 ± 16.4, respectively, with P = 0.001. Conclusion: Pre-operative oral gabapentin significantly reduced intra-operative remifentanil and sevoflurane requirements during hypotensive anaesthesia along with decreased post-operative analgesic requirement.

Radiation-induced cancer of the esophagus after postoperative irradiation for breast cancer

International Nuclear Information System (INIS)

Ito, Ichiro; Miyaishi, Kazuo; Mitsuhashi, Norio; Ito, Jun; Inoue, Tomio

1978-01-01

Two cases of radiation-induced cancer of the esophagus after postoperative irradiation for breast cancer were reported. Latent period of case 1 (cervical esophagus) was 12 years, and case 2 (middle thoracic esophagus) was 16 years. Radiographically the lesions were both serrated, and histologically, case 1 was ''poorly differentiated'' and case 2 was ''moderately differentiated'' squamous cell carcinoma. Histological types of basic breast cancer were both papillotubular carcinomas. Previous irradiation doses were 4180 rads for case 1 and 1860 rads for case 2. The esophageal cancers were remarkably improved by radiation therapy. It should be emphasized that radiation therapy is useful for the radiation-induced cancer of the esophagus. (author)

Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.

Science.gov (United States)

Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna; Martusevicius, Robertas; Nikolajsen, Lone; Dahl, Jørgen Berg; Mathiesen, Ole

2017-03-01

Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg·h or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval -59 to -25), P ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.

Effects of a new foam formulation of ketoprofen lysine salt in experimental models of inflammation and hyperalgesia.

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Daffonchio, L; Bestetti, A; Clavenna, G; Fedele, G; Ferrari, M P; Omini, C

1995-05-01

The anti-inflammatory and analgesic profile of a new topical foam formulation of ketoprofen lysine salt (CAS 57469-78-0, Artrosilene Schiuma, KLS-foam) was characterized in comparison with marketed gel formulations containing KLS (KLS-gel) or diclofenac diethylammonium salt (DCF-gel). KLS-foam dose-dependently inhibited oedema formation and hyperalgesia induced by subplantar injection of carrageenan or substance P, being more potent than KLS-gel. At equieffective anti-inflammatory doses, KLS-foam provided a more pronounced analgesic effect than DCF-gel. KLS-foam also markedly inhibited exudate formation and prostaglandin production induced by subcutaneous implantation of carrageenan soaked sponges. In carrageenan induced paw inflammation, KLS-foam provided the same anti-inflammatory effect as orally administered KLS, but induced significantly less gastric damages. Oral administration of KLS resulted in sustained systemic absorption of ketoprofen, whereas after topical application of KLS-foam no appreciable ketoprofen plasma levels were detected. These data support the anti-inflammatory and particularly the analgesic effectiveness of the new foam formulation of KLS, a finding that, together with the high gastric tolerability, further emphasizes the usefulness of KLS-foam in the treatment of localized flogistic diseases and associated pain.

Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

OpenAIRE

Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

2009-01-01

While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia t...

Laminectomy-induced arachnoradiculitis: a postoperative serial MRI study

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Matsui, H [Departments of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan); Tsuji, H [Departments of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan); Kanamori, M [Departments of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan); Kawaguchi, Y [Departments of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan); Yudoh, K [Departments of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan); Futatsuya, R [Departments of Radiology, Toyama Medical and Pharmaceutical University, Faculty of Medicine, Toyama (Japan)

1995-11-01

Time-related changes of laminectomy-induced cauda equina adhesions were investigated by MRI in ten patients with degenerative spinal disease who underwent posterior surgery to the lumbar spine; seven had disc herniations and three spinal stenosis. Axial MRI was performed before and 3, 7, 21 and 42 days after surgery. Cauda equina adhesions were most severe at the laminectomised levels L3-4, L4-5 and L5-S1 (n = 16); partial adhesions were found in 9 of 16 levels at 6 weeks after surgery. At the L3-4 or L5-S1 levels (n = 14), the area of laminar exposure without laminectomy, the cauda equina adhesions continued 1 week after surgery, but thereafter resolved; only partial adhesions were seen at 5 of 14 levels 6 weeks after surgery. Shrinkage of the arachnoid sac was also found at the level of the laminectomy, but it re-expanded 3 weeks after surgery in all cases. Cauda equina adhesions and shrinkage of the sac were correlated closely with laminectomy, with or without discectomy, suggesting that an inflammatory process of deep wound healing may be involved in the mechanism of a laminectomy-induced arachnoradiculitis which may be correlated with postoperative leg symptoms. (orig.). With 7 figs., 1 tab.

Laminectomy-induced arachnoradiculitis: a postoperative serial MRI study

International Nuclear Information System (INIS)

Matsui, H.; Tsuji, H.; Kanamori, M.; Kawaguchi, Y.; Yudoh, K.; Futatsuya, R.

1995-01-01

Time-related changes of laminectomy-induced cauda equina adhesions were investigated by MRI in ten patients with degenerative spinal disease who underwent posterior surgery to the lumbar spine; seven had disc herniations and three spinal stenosis. Axial MRI was performed before and 3, 7, 21 and 42 days after surgery. Cauda equina adhesions were most severe at the laminectomised levels L3-4, L4-5 and L5-S1 (n = 16); partial adhesions were found in 9 of 16 levels at 6 weeks after surgery. At the L3-4 or L5-S1 levels (n = 14), the area of laminar exposure without laminectomy, the cauda equina adhesions continued 1 week after surgery, but thereafter resolved; only partial adhesions were seen at 5 of 14 levels 6 weeks after surgery. Shrinkage of the arachnoid sac was also found at the level of the laminectomy, but it re-expanded 3 weeks after surgery in all cases. Cauda equina adhesions and shrinkage of the sac were correlated closely with laminectomy, with or without discectomy, suggesting that an inflammatory process of deep wound healing may be involved in the mechanism of a laminectomy-induced arachnoradiculitis which may be correlated with postoperative leg symptoms. (orig.). With 7 figs., 1 tab

Alfaxalone or ketamine-medetomidine in cats undergoing ovariohysterectomy: a comparison of intra-operative parameters and post-operative pain.

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Kalchofner Guerrero, Karin S; Reichler, Iris M; Schwarz, Andrea; Jud, Rahel S; Hässig, Michael; Bettschart-Wolfensberger, Regula

2014-11-01

To compare post-operative pain in cats after alfaxalone or ketamine- medetomidine anaesthesia for ovariohysterectomy (OHE) and physiologic parameters during and after surgery. Prospective 'blinded' randomized clinical study. Twenty-one healthy cats. Cats were assigned randomly into two groups: Group A, anaesthesia was induced and maintained with alfaxalone [5 mg kg(-1) intravenously (IV) followed by boli (2 mg kg(-1) IV); Group MK, induction with ketamine (5 mg kg(-1) IV) after medetomidine (30 μg kg(-1) intramuscularly (IM)], and maintenance with ketamine (2 mg kg(-1) IV). Meloxicam (0.2 mg kg(-1) IV) was administered after surgery. Basic physiological data were collected. At time T = -2, 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, and 24 hours post-operatively pain was assessed by three methods, a composite pain scale (CPS; 0-24 points), a visual analogue scale (VAS 0-100 mm), and a mechanical wound threshold (MWT) device. Butorphanol (0.2 mg kg(-1) IM) was administered if CPS was scored ≥13. Data were analyzed using a general linear model, Kruskal-Wallis analyses, Bonferroni-Dunn test, unpaired t-test and Fisher's exact test as relevant. Significance was set at p ketamine-medetomidine was found to provide better post-surgical analgesia than alfaxalone in cats undergoing OHE; however, primary hyperalgesia developed in both groups. Alfaxalone is suitable for induction and maintenance of anaesthesia in cats undergoing OHE, but administration of additional sedative and analgesic drugs is highly recommended. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil.

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Prontera, Andrea; Baroni, Stefano; Marudi, Andrea; Valzania, Franco; Feletti, Alberto; Benuzzi, Francesca; Bertellini, Elisabetta; Pavesi, Giacomo

2017-01-01

Awake craniotomy allows continuous monitoring of patients' neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic-sedative medication is increasing. Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used.

Total intravenous anesthesia with propofol and remifentanil in a patient with MELAS syndrome -A case report-.

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Park, Jin Suk; Baek, Chong Wha; Kang, Hyun; Cha, Su Man; Park, Jung Won; Jung, Yong Hun; Woo, Young-Cheol

2010-04-01

A 23-year-old woman with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) underwent a laparoscopy-assisted appendectomy. MELAS syndrome is a multisystemic disease caused by mitochondrial dysfunction. General anesthesia has several potential hazards to patients with MELAS syndrome, such as malignant hyperthermia, hypothermia, and metabolic acidosis. In this case, anesthesia was performed with propofol, remifentanil TCI, and atracurium without any surgical or anesthetic complications. We discuss the anesthetic effects of MELAS syndrome.

Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A(1) receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway.

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Zhang, Xiao-Jun; Chen, Hong-Li; Li, Zhi; Zhang, Hong-Qi; Xu, Hong-Xi; Sung, Joseph J Y; Bian, Zhao-Xiang

2009-11-01

Paeoniflorin (PF), a chief active ingredient in the root of Paeonia lactiflora Pall (family Ranunculaceae), is effective in relieving colorectal distention (CRD)-induced visceral pain in rats with visceral hyperalgesia induced by neonatal maternal separation (NMS). This study aimed at exploring the underlying mechanisms of PF's analgesic effect on CRD-evoked nociceptive signaling in the central nervous system (CNS) and investigating whether the adenosine A(1) receptor is involved in PF's anti-nociception. CRD-induced visceral pain as well as phosphorylated-extracellular signal-regulated protein kinase (p-ERK) and phospho-cAMP response element-binding protein (p-CREB) expression in the CNS structures of NMS rats were suppressed by NMDA receptor antagonist dizocilpine (MK-801) and ERK phosphorylation inhibitor U0126. PF could similarly inhibit CRD-evoked p-ERK and c-Fos expression in laminae I-II of the lumbosacral dorsal horn and anterior cingulate cortex (ACC). PF could also reverse the CRD-evoked increased glutamate concentration by CRD as shown by dynamic microdialysis monitoring in ACC, whereas, DPCPX, an antagonist of adenosine A(1) receptor, significantly blocked the analgesic effect of PF and PF's inhibition on CRD-induced p-ERK and p-CREB expression. These results suggest that PF's analgesic effect is possibly mediated by adenosine A(1) receptor by inhibiting CRD-evoked glutamate release and the NMDA receptor dependent ERK signaling.

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I).

Science.gov (United States)

Huge, Volker; Lauchart, Meike; Förderreuther, Stefanie; Kaufhold, Wibke; Valet, Michael; Azad, Shahnaz Christina; Beyer, Antje; Magerl, Walter

2008-07-23

Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group. 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed. In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

Predictive performance of the 'Minto' remifentanil pharmacokinetic parameter set in morbidly obese patients ensuing from a new method for calculating lean body mass.

Science.gov (United States)

La Colla, Luca; Albertin, Andrea; La Colla, Giorgio; Porta, Andrea; Aldegheri, Giorgio; Di Candia, Domenico; Gigli, Fausto

2010-01-01

In a previous article, we showed that the pharmacokinetic set of remifentanil used for target-controlled infusion (TCI) might be biased in obese patients because it incorporates flawed equations for the calculation of lean body mass (LBM), which is a covariate of several pharmacokinetic parameters in this set. The objectives of this study were to determine the predictive performance of the original pharmacokinetic set, which incorporates the James equation for LBM calculation, and to determine the predictive performance of the pharmacokinetic set when a new method to calculate LBM was used (the Janmahasatian equations). This was an observational study with intraoperative observations and no follow-up. Fifteen morbidly obese inpatients scheduled for bariatric surgery were included in the study. The intervention included manually controlled continuous infusion of remifentanil during the surgery and analysis of arterial blood samples to determine the arterial remifentanil concentration, to be compared with concentrations predicted by either the unadjusted or the adjusted pharmacokinetic set. The statistical analysis included parametric and non-parametric tests on continuous variables and determination of the median performance error (MDPE), median absolute performance error (MDAPE), divergence and wobble. The median values (interquartile ranges) of the MDPE, MDAPE, divergence and wobble for the James equations during maintenance were -53.4% (-58.7% to -49.2%), 53.4% (49.0-58.7%), 3.3% (2.9-4.7%) and 1.4% h(-1) (1.1-2.5% h(-1)), respectively. The respective values for the Janmahasatian equations were -18.9% (-24.2% to -10.4%), 20.5% (13.3-24.8%), 2.6% (-0.7% to 4.5%) and 1.9% h(-1) (1.4-3.0% h(-1)). The performance (in terms of the MDPE and MDAPE) of the corrected pharmacokinetic set was better than that of the uncorrected one. The predictive performance of the original pharmacokinetic set is not clinically acceptable. Use of a corrected LBM value in morbidly obese

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

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Su Lin

2011-11-01

Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

Transcutaneous electrical nerve stimulation attenuates CFA-induced hyperalgesia and inhibits spinal ERK1/2-COX-2 pathway activation in rats.

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Fang, Jun-Fan; Liang, Yi; Du, Jun-Ying; Fang, Jian-Qiao

2013-06-15

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacologic treatment for pain relief. In previous animal studies, TENS effectively alleviated Complete Freund's Adjuvant (CFA)- or carrageenan-induced inflammatory pain. Although TENS is known to produce analgesia via opioid activation in the brain and at the spinal level, few reports have investigated the signal transduction pathways mediated by TENS. Prior studies have verified the importance of the activation of extracellular signal-regulated kinase (ERK) signal transduction pathway in the spinal cord dorsal horn (SCDH) in acute and persistent inflammatory pains. Here, by using CFA rat model, we tested the efficacy of TENS on inhibiting the expressions of p-ERK1/2 and of its downstream cyclooxygenase-2 (COX-2) and the level of prostaglandin E2 (PGE2) at spinal level. Rats were randomly divided into control, model and TENS groups, and injected subcutaneously with 100 μl CFA or saline in the plantar surface of right hind paw. Rats in the TENS group were treated with TENS (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 to 2 mA, lasting for 30 min each time) at 5 h and 24 h after injection. Paw withdrawal thresholds (PWTs) were measured with dynamic plantar aesthesiometer at 3d before modeling and 5 h, 6 h, and 25 h after CFA injection. The ipsilateral sides of the lumbar spinal cord dosral horns were harvested for detecting the expressions of p-ERK1/2 and COX-2 by western blot analysis and qPCR, and PGE2 by ELISA. CFA-induced periphery inflammation decreased PWTs and increased paw volume of rats. TENS treatment significantly alleviated mechanical hyperalgesia caused by CFA. However, no anti-inflammatory effect of TENS was observed. Expression of p-ERK1/2 protein and COX-2 mRNA was significantly up-regualted at 5 h and 6 h after CFA injection, while COX-2 and PGE2 protein level only increased at 6 h after modeling. Furthermore, the high expression of p-ERK1

Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration?

DEFF Research Database (Denmark)

Sjøgren, P; Thunedborg, L P; Christrup, Lona Louring

1998-01-01

Recently, clinical reports have suggested a relationship between the occurrence of hyperalgesia, allodynia and/or myoclonus and treatment with high doses of morphine in humans. Although few clinical descriptions of these phenomena are available, experimental work supports the notion that high dos...

Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I.

Directory of Open Access Journals (Sweden)

Volker Huge

Full Text Available BACKGROUND: Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS. In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST in comparison to an age and gender matched control group. METHODS: 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT, the heat and cold pain thresholds (HPT; CPT and the occurrence of paradoxical heat sensation (PHS were observed. RESULTS: In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb. CONCLUSIONS: We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

Bilateral hand/wrist heat and cold hyperalgesia, but not hypoesthesia, in unilateral carpal tunnel syndrome.

Science.gov (United States)

de la Llave-Rincón, Ana Isabel; Fernández-de-las-Peñas, César; Fernández-Carnero, Josué; Padua, Luca; Arendt-Nielsen, Lars; Pareja, Juan A

2009-10-01

The aim of the current study was to evaluate bilaterally warm/cold detection and heat/cold pain thresholds over the hand/wrist in patients with carpal tunnel syndrome (CTS). A total of 25 women with strictly unilateral CTS (mean 42 +/- 10 years), and 20 healthy matched women (mean 41 +/- 8 years) were recruited. Warm/cold detection and heat/cold pain thresholds were assessed bilaterally over the carpal tunnel and the thenar eminence in a blinded design. Self-reported measures included both clinical pain history (intensity, location and area) and Boston Carpal Tunnel Questionnaire. No significant differences between groups for both warm and cold detection thresholds in either carpal tunnel or thenar eminence (P > 0.5) were found. Further, significant differences between groups, but not between sides, for both heat and cold pain thresholds in both the carpal tunnel and thenar eminence were found (all P < 0.001). Heat pain thresholds (P < 0.01) were negatively correlated, whereas cold pain thresholds (P < 0.001) were positively correlated with hand pain intensity and duration of symptoms. Our findings revealed bilateral thermal hyperalgesia (lower heat pain and reduced cold pain thresholds) but not hypoesthesia (normal warm/cold detection thresholds) in patients with strictly unilateral CTS when compared to controls. We suggest that bilateral heat and cold hyperalgesia may reflect impairments in central nociceptive processing in patients with unilateral CTS. The bilateral thermal hyperalgesia associated with pain intensity and duration of pain history supports a role of generalized sensitization mechanisms in the initiation, maintenance and spread of pain in CTS.

Postoperative Ileus in the Elderly

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Chih-Peng Tu

2014-03-01

Full Text Available Postoperative ileus is among the most common complications after surgery. Aging is associated with an increased colonic transit time, and anesthetic disturbance to colonic motility is often aggravated in the elderly. Postoperative ileus increases morbidity, prolongs the length of hospital stay, and constitutes a significant economic burden on the healthcare system. Multimodal enhanced recovery protocols, or fast-track surgeries, have been developed to improve postoperative recovery. Patient education, avoidance of perioperative fluid overload, selective use of nasogastric decompression, early ambulation, adopting a minimally invasive approach, early initiation of clear fluids, and gum chewing are all possible measures to reduce postoperative ileus. Thoracic epidural anesthesia is a well-established technique to hasten recovery, whereas insufficient data are available to ascertain the safety and efficacy of opioid-sparing analgesia in the elderly. The evidence is clear that traditional prokinetic medications are not helpful in the treatment or prevention of postoperative ileus. Early results suggest that alvimopan is a promising agent to reverse opioid-induced ileus. Since postoperative ileus is a multifactorial condition, a concerted effort is therefore necessary to prevent or decrease the duration of postoperative ileus using multimodal strategies.

Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

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Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

2014-01-01

The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

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Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

2014-09-01

Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

Pre-emptive oral dexmethorphan reduces fentanyl-induced cough as well as immediate postoperative adrenocortico-tropic hormone and growth hormone level

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Avik Mukherjee

2011-01-01

Full Text Available Background : Fentanyl-induced cough is not always benign and brief and can be remarkably troublesome, spasmodic, and explosive. Dextromethorphan, an opioid derivative with an antitussive action, may be effective in reducing the fentanyl-induced cough. Dextromethorphan, a N-methyl D aspartate receptor antagonist, may have some effect on diminishing the stress response to surgery. This study was undertaken to determine whether preoperative dextromethorphan could effectively attenuate its incidence, severity, and effect on postoperative stress hormone levels. Materials and Methods : Three hundred and twenty patients of American society of anesthesiologists I-II, aged 18-60 years, undergoing elective laparoscopic cholecystectomy or appendicectomy were randomly allocated into two groups (Group C, control; Group D, dextromethorphan consisting of 160 patients each. Patients in Group D received dextromethorphan 40 mg orally and in Group C received placebo tablets 60 minutes before induction of anesthesia. The incidence of cough was recorded for 1 minute after fentanyl injection and graded as none (0, mild (1-2, moderate (3-5, and severe (>5 cough. Blood samples were collected for estimation of stress hormone levels before surgery and again at 1 hour and 24 hours postoperatively and compared. The appearance of adverse reactions was recorded. Results : The incidence of reflex fentanyl cough was lower in dextromethorphan group (3.9% in comparison to placebo (59.8%. Five patients developed mild and one moderate cough in the dextromethorphan group. In the control group, 31 patients developed mild, 29 moderate, and 32 severe cough. The stress hormones were significantly higher at 1 hour and 24 hours postoperatively in both groups in comparison to its preoperative values. However, at 1 hour postoperatively, adrenocorticotropic hormone, epinephrine, and growth hormone values were significantly low in the dextromethorphan group (61.5 ± 21.1 pg/ ml, 142.1 ± 11

Reduced anaesthetic requirements and postoperative analgesics in patients undergoing laparoscopic cholecystectomy: premedication with intravenous paracetamol versus ketorolac, a double blind and randomised clinical trial.

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Medina-Vera, A J; Novoa, L M

2017-02-01

To compare the effects of premedication with intravenous paracetamol versus ketorolac, in decreasing intraoperative anaesthetic and postoperative opioid analgesics requirements in patients undergoing laparoscopic cholecystectomy. An experimental, prospective, comparative, double blind, and randomised clinical trial was conducted to determine intraoperative opioid requirements, and pain and analgesic requirements in the postoperative period in 100 healthy patients undergoing laparoscopic cholecystectomy. They were randomised into 2 groups: Group 1: pre-medicated with paracetamol 1g, and Group 2: with ketorolac 30mg (both administered intravenously 30minutes prior to surgery). There were no statistically significant differences between groups as regards intraoperative remifentanil use (Group 1: 0.0739±0.016μg/kg/min, Group 2: 0.0741±0.018μg/kg/min). The number of patients in Group 2 that had values of VAS>4 points (22.4%) was lower than in Group 1 (28.6%), but with no statistically significant difference. Of the patients who needed postoperative opioid rescue, most required a single rescue and application of analgesics during hospitalisation, that prevailed between 3 and 12hours, without any significant differences between groups. No adverse effects were observed in the study sample. Paracetamol 1g IV given preoperatively decreased anaesthetic requirements and the need for postoperative analgesics similar to the preoperative administration of ketorolac 30mg IV. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats

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Angela Maria Sousa

2015-06-01

Full Text Available BACKGROUND AND OBJECTIVES: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. METHODS: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 µg or 0.9% NaCl, rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. RESULTS: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. CONCLUSIONS: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors.

Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients.

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Kim, Sung-Hoon; Jin, Seok-Joon; Karm, Myong-Hwan; Moon, Young-Jin; Jeong, Hye-Won; Kim, Jae-Won; Ha, Seung-Il; Kim, Joung-Uk

2016-08-01

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

A case of likely radiation-induced synchronous esophageal and skin carcinoma following post-operative radiation for breast cancer

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Kanogawa, Naoya; Shimada, Hideaki; Kainuma, Osamu; Cho, Akihiro; Yamamoto, Hiroshi; Itami, Makiko; Nagata, Matsuo

2009-01-01

A 71-year-old woman was admitted in January 2008 with on upper thoracic esophageal squamous cell carcinoma and a right chest wall skin tumor. When she was 32 years old, she had a radical mastectomy for right breast cancer and received postoperative radiation. Due to the presence of lung adhesions, trans-thoracic esophagectomy could not be done; thus, a blunt dissection was performed. She was discharged on the 19 th postoperative day. On pathology, a pT2N0M0 (pStage II) esophageal tumor was diagnosed. A resection of her skin tumor underwent 79 days after the esophageal surgery; on pathology, the skin tumor was diagnosed as a basal cell carcinoma. Since the esophageal tumor and the skin tumor occurred in the same area that had received radiation therapy, these tumors were diagnosed as being radiation-induced secondary tumors. In the English language medical literature, several reports of radiation-induced esophageal cancer occurring as a second cancer after radiotherapy for breast cancer have been published. Radiation-induced esophageal cancer rates may increase in Japan given the number of women who previously received radiotherapy for breast cancer. (author)

Calotropis procera Latex-Induced Inflammatory Hyperalgesia—Effect of Antiinflammatory Drugs

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Raman Sehgal

2005-01-01

Full Text Available The milky white latex of plant Calotropis procera produces inflammation of the skin and mucous membranes on accidental exposure. It produces edema on local administration due to the release of histamine and prostaglandins and is associated with hyperalgesia. In the present study we have evaluated the antiedematous and analgesic activity of antiinflammatory drugs against inflammatory response induced by dried latex (DL of C procera in rat paw edema model. An aqueous extract of DL of C procera was injected into the subplantar surface of the rat paw and the paw volume was measured by a plethysmometer at 0, 1, 2, 6, 12, and 24 hours. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test, compression test, and observing the grooming behavior. The inhibitory effect of diclofenac and rofecoxib on edema formation and hyperalgesic response was compared with cyproheptadine (CPH. DL-induced edema formation was maximum at 2 hours that was associated with decreased pain threshold, functional impairment, and grooming. Treatment with antiinflammatory drugs and CPH significantly attenuated the edematous response and grooming, increased the pain threshold, and improved functional parameters. Both antiinflammatory and antiserotonergic drugs significantly inhibited the hyperalgesia associated with DL-induced paw edema. Rofecoxib was found to be superior than diclofenac and was as effective as CPH in ameliorating the hyperalgesia. However, it was found to be less effective than CPH in attenuating edema formation.

Analgesic effects of ultrasound-guided transverse abdominis plane block using different volumes and concentrations of local analgesics after laparoscopic cholecystectomy.

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Şahin, Ayça Sultan; Ay, Necmiye; Şahbaz, Nuri Alper; Akay, Mehlika Kocabaş; Demiraran, Yavuz; Derbent, Abdurrahim

2017-02-01

Objective To evaluate the effects of an ultrasound-guided transverse abdominis plane (US-TAP) block used for postoperative pain relief by comparing the efficacy of two different volumes/concentrations of the local anaesthetic bupivacaine in patients undergoing laparoscopic cholecystectomies. Methods This randomized study enrolled patients undergoing laparoscopic cholecystectomies. They were randomized to two groups: group A received a 20 ml US-TAP block (50 mg bupivacaine +10 ml saline solution) and group B received a 30 ml US-TAP block (50 mg bupivacaine + 20 ml saline solution). The intraoperative consumption of remifentanil, the requirement for postoperative rescue analgesics, patient satisfaction scores, postoperative complications, and postoperative pain as measured by a visual analogue scale at 20 min, 12 h, and 24 h were recorded. Results A total of 60 patients enrolled in the study. There were no differences between the two groups with respect to demographic characteristics, duration of anaesthesia and patient satisfaction scores. The intraoperative consumption of remifentanil, postoperative VAS scores (20 min, 12 h and 24 h) and the requirement for postoperative analgesics were all significantly lower in group B who received a larger volume but a lower concentration of local anaesthetic solution compared with group A. Conclusion A US-TAP block can form part of a balanced postoperative analgesic regimen following laparoscopic cholecystectomy.

Cutaneous C-polymodal fibers lacking TRPV1 are sensitized to heat following inflammation, but fail to drive heat hyperalgesia in the absence of TPV1 containing C-heat fibers

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Koerber H Richard

2010-09-01

Full Text Available Abstract Background Previous studies have shown that the TRPV1 ion channel plays a critical role in the development of heat hyperalgesia after inflammation, as inflamed TRPV1-/- mice develop mechanical allodynia but fail to develop thermal hyperalgesia. In order to further investigate the role of TRPV1, we have used an ex vivo skin/nerve/DRG preparation to examine the effects of CFA-induced-inflammation on the response properties of TRPV1-positive and TRPV1-negative cutaneous nociceptors. Results In wildtype mice we found that polymodal C-fibers (CPMs lacking TRPV1 were sensitized to heat within a day after CFA injection. This sensitization included both a drop in average heat threshold and an increase in firing rate to a heat ramp applied to the skin. No changes were observed in the mechanical response properties of these cells. Conversely, TRPV1-positive mechanically insensitive, heat sensitive fibers (CHs were not sensitized following inflammation. However, results suggested that some of these fibers may have gained mechanical sensitivity and that some previous silent fibers gained heat sensitivity. In mice lacking TRPV1, inflammation only decreased heat threshold of CPMs but did not sensitize their responses to the heat ramp. No CH-fibers could be identified in naïve nor inflamed TRPV1-/- mice. Conclusions Results obtained here suggest that increased heat sensitivity in TRPV1-negative CPM fibers alone following inflammation is insufficient for the induction of heat hyperalgesia. On the other hand, TRPV1-positive CH fibers appear to play an essential role in this process that may include both afferent and efferent functions.

[Post-operative pain after ultrasound transversus abdominis plane block versus trocar site infiltration in laparoscopic nephrectomy: a prospective study].

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Araújo, Ana M; Guimarães, Joana; Nunes, Catarina S; Couto, Paula S; Amadeu, Eduarda

Transversus abdominis plane (TAP) block is useful in reducing post-operative pain in laparoscopic nephrectomy compared to placebo. The purpose of this work is to compare post-operative pain and recovery after TAP block or trocar site infiltration (TSI) in this surgery. A prospective, single blinded study on patients scheduled for laparoscopic nephrectomy. Patients were assigned to two groups: TSI Group: trocar site infiltration at the end of surgery; TAP Group: unilateral ultrasound-guided TAP block after induction. Sevoflurane and remifentanil, in a target controlled infusion mode, were used for maintenance of general anesthesia. Before the end of surgery paracetamol, tramadol and morphine were administered. Visual analogue scale (VAS 0-100mm) at rest and with cough was applied in three moments: in recovery room (T1 at admission and T2 before discharge) and 24h after surgery (T3). Pain scores with incentive spirometer were also evaluated at T3. In recovery, morphine was administered as a rescue drug whenever VAS>30mm. Time to oral intake, chair sitting, ambulation and length of hospital stay were evaluated 24h after surgery. Student's t-test and Chi-square test, and linear regression models. A p-value0.05). VAS at rest (TAP vs. TSI groups) was: T1=33±29 vs. 39±32, T2=10±9 vs. 17±18 and T3=7±12 vs. 10±18. VAS with cough (TAP vs. TSI groups) was: T1=51±34 vs. 45±32, T2=24±24 vs. 33±23 and T3=20±23 vs. 23±23. VAS with incentive spirometer (TAP vs. TSI groups) was: T3=21±27 vs. 21±25. Intraoperative remifentanil consumption was similar between TAP (0.16±0.07mcg.kg -1 .min -1 ) and TSI (0.18±0.9mcg.kg -1 .min -1 ) groups. There were no differences in opioid consumption between TAP (4.4±3.49mg) and TSI (6.87±4.83mg) groups during recovery. Functional recovery parameters were not statistically different between groups. Multimodal analgesia with TAP block did not show a significant clinical benefit compared with trocar site infiltration in laparoscopic

Post-operative pain after ultrasound transversus abdominis plane block versus trocar site infiltration in laparoscopic nephrectomy: a prospective study

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Ana M. Araújo

Full Text Available Abstract Background Transversus abdominis plane (TAP block is useful in reducing post-operative pain in laparoscopic nephrectomy compared to placebo. The purpose of this work is to compare post-operative pain and recovery after TAP block or trocar site infiltration (TSI in this surgery. Methods A prospective, single blinded study on patients scheduled for laparoscopic nephrectomy. Patients were assigned to two groups: TSI Group: trocar site infiltration at the end of surgery; TAP Group: unilateral ultrasound-guided TAP block after induction. Sevoflurane and remifentanil, in a target controlled infusion mode, were used for maintenance of general anesthesia. Before the end of surgery paracetamol, tramadol and morphine were administered. Visual analogue scale (VAS 0-100 mm at rest and with cough was applied in three moments: in recovery room (T1 at admission and T2 before discharge and 24 h after surgery (T3. Pain scores with incentive spirometer were also evaluated at T3. In recovery, morphine was administered as a rescue drug whenever VAS > 30 mm. Time to oral intake, chair sitting, ambulation and length of hospital stay were evaluated 24 h after surgery. Statistical analysis: Student's t-test and Chi-square test, and linear regression models. A p-value 0.05. VAS at rest (TAP vs. TSI groups was: T1 = 33 ± 29 vs. 39 ± 32, T2 = 10 ± 9 vs. 17 ± 18 and T3 = 7 ± 12 vs. 10 ± 18. VAS with cough (TAP vs. TSI groups was: T1 = 51 ± 34 vs. 45 ± 32, T2 = 24 ± 24 vs. 33 ± 23 and T3 = 20 ± 23 vs. 23 ± 23. VAS with incentive spirometer (TAP vs. TSI groups was: T3 = 21 ± 27 vs. 21 ± 25. Intraoperative remifentanil consumption was similar between TAP (0.16 ± 0.07 mcg.kg-1.min-1 and TSI (0.18 ± 0.9 mcg.kg-1.min-1 groups. There were no differences in opioid consumption between TAP (4.4 ± 3.49 mg and TSI (6.87 ± 4.83 mg groups during recovery. Functional recovery parameters were not statistically different between groups. Conclusions Multimodal

Early postoperative cognitive dysfunction and postoperative delirium after anaesthesia with various hypnotics: study protocol for a randomised controlled trial - The PINOCCHIO trial

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Spinelli Allison

2011-07-01

Full Text Available Abstract Background Postoperative delirium can result in increased postoperative morbidity and mortality, major demand for postoperative care and higher hospital costs. Hypnotics serve to induce and maintain anaesthesia and to abolish patients' consciousness. Their persisting clinical action can delay postoperative cognitive recovery and favour postoperative delirium. Some evidence suggests that these unwanted effects vary according to each hypnotic's specific pharmacodynamic and pharmacokinetic characteristics and its interaction with the individual patient. We designed this study to evaluate postoperative delirium rate after general anaesthesia with various hypnotics in patients undergoing surgical procedures other than cardiac or brain surgery. We also aimed to test whether delayed postoperative cognitive recovery increases the risk of postoperative delirium. Methods/Design After local ethics committee approval, enrolled patients will be randomly assigned to one of three treatment groups. In all patients anaesthesia will be induced with propofol and fentanyl, and maintained with the anaesthetics desflurane, or sevoflurane, or propofol and the analgesic opioid fentanyl. The onset of postoperative delirium will be monitored with the Nursing Delirium Scale every three hours up to 72 hours post anaesthesia. Cognitive function will be evaluated with two cognitive test batteries (the Short Memory Orientation Memory Concentration Test and the Rancho Los Amigos Scale preoperatively, at baseline, and postoperatively at 20, 40 and 60 min after extubation. Statistical analysis will investigate differences in the hypnotics used to maintain anaesthesia and the odds ratios for postoperative delirium, the relation of early postoperative cognitive recovery and postoperative delirium rate. A subgroup analysis will be used to categorize patients according to demographic variables relevant to the risk of postoperative delirium (age, sex, body weight and to the

Estudo prospectivo das repercussões de baixas doses de remifentanil na função sinoatrial e na condução e refratariedade cardíaca Estudio prospectivo de las repercusiones de bajas dosis de remifentanil en la función sinoatrial en la conducción y refractariedad cardiaca Prospective study on the repercussions of low doses of remifentanil on sinoatrial function and in cardiac conduction and refractory period

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Simone Soares Leite

2007-10-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: O remifentanil é um opióide com início e término de ação rápidos, cujo uso em procedimentos de curta duração vem se propagando nos últimos anos. Entre os efeitos colaterais descritos, há relatos de bradicardia e assistolia. O objetivo deste estudo foi avaliar os efeitos desse fármaco na condução e refratariedade cardíaca, em humanos. MÉTODO: Estudo prospectivo de 16 pacientes, entre 18 e 65 anos, de ambos os sexos, ASA I a III, submetidos a estudo eletrofisiológico intracardíaco eletivo. Foram excluídos os pacientes com doença do nódulo sinoatrial e os portadores de bloqueios cardíacos graves. No laboratório de eletrofisiologia, os pacientes foram inicialmente sedados com midazolam (0,03 mg.kg-1, após 5 minutos (M0 avaliou-se o grau de sedação de intensidade de dor, pressões arteriais sistólica e diastólica, freqüências cardíaca e respiratória e saturação de oxigênio. O eletrofisiologista avaliou as variáveis de condução cardíaca (duração do QRS, intervalos AA, AH, HV e PA, o tempo de recuperação do nódulo sinoatrial e as variáveis de refratariedade cardíaca (período refratário do átrio direito, período refratário do ventrículo direito e período refratário do nódulo atrioventricular. Após as medidas iniciais o remifentanil foi introduzido (bolus de 0,5 µg.kg-1 + infusão de 0,05 µg.kg-1.min-1 e após 20 minutos as mesmas variáveis foram reavaliadas (M1. RESULTADOS: Observou-se diminuição das pressões sistólica e diastólica (p = 0,0001 entre M0 e M1, sem diferença estatística significativa da freqüência respiratória ou da saturação de oxigênio. Houve aumento do intervalo átrio-His (p = 0,006 e do tempo de recuperação do nódulo sinoatrial (p = 0,0004, do período refratário do átrio direito (p = 0,001 e do período refratário do nódulo atrioventricular (p = 0,0001, porém não houve diminuição da freqüência cardíaca basal entre M0 e M1

Effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain induced by CFA adjuvant

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Vida Nazemian

2016-07-01

Full Text Available Background: Rheumatoid arthritis is a type of inflammatory pain and is an autoimmune and chronic inflammatory disease which can lead to hyperalgesia, edema and decreased motor activity in affected area. Mesenchymal stem cells conditioned medium (MSC-CM has anti-inflammatory mediators which can regulate the immune responses, alleviate inflammatory symptoms and has a paracrine effects too. The aim of this study was to evaluate the effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain which induced by CFA adjuvant.Materials and Methods: Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by single subcutaneous injection of CFA into the rats hind paw on day zero. MSC-CM was administered daily and intraperitoneal during the 21 days of the study after CFA injection. Hyperalgesia and edema were assessed on days 0, 7, 14 and 21 of the study respectively with radian heat and plethysmometer instrument.Results: The results of this study indicated the significant roles of MSC-CM in betterment of inflammatory symptoms such as hyperalgesia and edema during different stages of inflammation caused by CFA. The continuing injection of MSC-CM could reduce the inflammatory symptoms.Conclusion: Long term treatment by MSC-CM can alleviate hyperalgesia and edema and decrease those to the level of the time before induction of inflammation.   

Remifentanil-propofol analgo-sedation shortens duration of ventilation and length of ICU stay compared to a conventional regimen: A centre randomised, cross-over, open-label study in the Netherlands

NARCIS (Netherlands)

F.W. Rozendaal (Frans); P.E. Spronk (Peter); F.F. Snellen (Ferdinand); A. Schoen (Adri); A.R.H. van Zanten (Arthur); N.A. Foudraine (Norbert); P.G.H. Mulder (Paul); J. Bakker (Jan)

2009-01-01

textabstractObjective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia. Design: Centre randomised, open-label, crossover, 'real-life' study. Setting: 15 Dutch hospitals.

Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

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Junqueira, Daniela R; Zorzela, Liliane M; Perini, Edson

2017-04-21

Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use

100-Hz Electroacupuncture but not 2-Hz Electroacupuncture is Preemptive Against Postincision Pain in Rats.

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Silva, Marcelo Lourenço; Silva, Josie Resende Torres; Prado, Wiliam Alves

2016-08-01

Preemptive analgesia involves introducing an analgesic before noxious stimulation. Electroacupuncture (EA) activates descending mechanisms that modulate nociceptive inputs into the spinal dorsal horn. This study evaluated whether preoperative EA is more effective than postoperative EA in reducing incision pain in rats. The nociceptive threshold to mechanical stimulation was utilized to examine the effects of an intraperitoneal injection of saline (0.1 mL/kg) or naloxone (1 mg/kg) on antinociception induced by a 20-minute period of 2-Hz or 100-Hz EA applied to the Zusanli (ST36) and Sanyinjiao (SP6) acupoints before surgical incision, or 10 minutes after or 100 minutes after surgical incision of the hind paw. The extent of mechanical hyperalgesia after the incision was significantly attenuated by the application of 100-Hz EA preoperatively, but not by its application at 10 minutes or 100 minutes postoperatively. By contrast, 2-Hz EA was effective against postoperative hyperalgesia when applied 10 minutes or 100 minutes after surgery but not when it was applied preoperatively. Only the effect of 2-Hz EA applied 10 minutes after surgery was sensitive to naloxone. The present study showed for the first time that 100-Hz EA, but not 2-Hz EA, exerts a nonopioidergic preemptive effect against postincision pain in rats. Copyright © 2016. Published by Elsevier B.V.

Opioid-Induced Nausea Involves a Vestibular Problem Preventable by Head-Rest.

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Nadine Lehnen

Full Text Available Opioids are indispensable for pain treatment but may cause serious nausea and vomiting. The mechanism leading to these complications is not clear. We investigated whether an opioid effect on the vestibular system resulting in corrupt head motion sensation is causative and, consequently, whether head-rest prevents nausea.Thirty-six healthy men (26.6 ± 4.3 years received an opioid remifentanil infusion (45 min, 0.15 μg/kg/min. Outcome measures were the vestibulo-ocular reflex (VOR gain determined by video-head-impulse-testing, and nausea. The first experiment (n = 10 assessed outcome measures at rest and after a series of five 1-Hz forward and backward head-trunk movements during one-time remifentanil administration. The second experiment (n = 10 determined outcome measures on two days in a controlled crossover design: (1 without movement and (2 with a series of five 1-Hz forward and backward head-trunk bends 30 min after remifentanil start. Nausea was psychophysically quantified (scale from 0 to 10. The third controlled crossover experiment (n = 16 assessed nausea (1 without movement and (2 with head movement; isolated head movements consisting of the three axes of rotation (pitch, roll, yaw were imposed 20 times at a frequency of 1 Hz in a random, unpredictable order of each of the three axes. All movements were applied manually, passively with amplitudes of about ± 45 degrees.The VOR gain decreased during remifentanil administration (p<0.001, averaging 0.92 ± 0.05 (mean ± standard deviation before, 0.60 ± 0.12 with, and 0.91 ± 0.05 after infusion. The average half-life of VOR recovery was 5.3 ± 2.4 min. 32/36 subjects had no nausea at rest (nausea scale 0.00/0.00 median/interquartile range. Head-trunk and isolated head movement triggered nausea in 64% (p<0.01 with no difference between head-trunk and isolated head movements (nausea scale 4.00/7.25 and 1.00/4.5, respectively.Remifentanil reversibly decreases VOR gain at a half

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model.

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Gao, Y H; Li, C W; Wang, J Y; Tan, L H; Duanmu, C L; Jing, X H; Chang, X R; Liu, J L

2017-06-01

Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

PREEMPTIVE SINGLE-DOSE PREGABALIN IN MODULATION OF POSTOPERATIVE PAIN AND OPIOID REQUIREMENT AFTER LAPAROSCOPIC CHOLECYSTECTOMY- A RANDOMIZED CLINICAL STUDY

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Rajib Hazarika

2018-01-01

Full Text Available BACKGROUND With the enormous advancement in the field of laparoscopic cholecystectomy, postoperative pain has substantially reduced as compared to open procedures. However, postoperative pain is still the most frequent complaint, which can hamper recovery, mandate inpatient admission and thereby increase the cost of such care. Preemptive analgesia attenuates sensitisation of pain before surgery so as to reduce postoperative hyperalgesia and allodynia. Pregabalin is a structural analog of γ-aminobutyric acid, which shows analgesic, anticonvulsant, and anxiolytic effects. The aim of the present study was to evaluate the effectiveness of preemptive oral pregabalin on postoperative pain and opioid consumption in patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS Eighty adult patients of ASA I and II undergoing laparoscopic cholecystectomy were randomly divided into two groups to receive either pregabalin 150 mg capsule or a matching placebo (vitamin B complex capsule 1 hour before surgery. Anaesthesia technique was standardised in both the groups. Postoperative pain was assessed at 0, 1, 2, 3, 6, 9, 12, 18 and 24 hours period postoperatively by a 10 cm visual analogue scale, where 0, no pain; 10, worst imaginable pain. Subjects received Inj. Tramadol hydrochloride (1 mg/kg IV as a rescue analgesic whenever VAS score was ≥4. Occurrence of any side effects like nausea, vomiting, sedation, headache and dizziness was also noted. Statistical Analysis Used- Data analysis was done using PASW 18.0 software. Results were analysed by Mann-Whitney U-test, large sample difference in proportion test and Fisher’s Exact test. RESULTS Patients in the pregabalin group had significantly lower pain scores at all the time intervals in comparison to placebo group (p<0.05. Total postoperative tramadol consumption in the pregabalin group was statistically significantly lower than in the control group (p<0.05 and also time to first request for

Fosaprepitant versus ondansetron for the prevention of postoperative nausea and vomiting in patients who undergo gynecologic abdominal surgery with patient-controlled epidural analgesia: a prospective, randomized, double-blind study.

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Soga, Tomohiro; Kume, Katsuyoshi; Kakuta, Nami; Hamaguchi, Eisuke; Tsutsumi, Rie; Kawanishi, Ryosuke; Fukuta, Kohei; Tanaka, Katsuya; Tsutsumi, Yasuo M

2015-10-01

Postoperative nausea and vomiting (PONV) is the most common postoperative complication. The postoperative use of opioids is known to increase the incidence. We compared fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, and ondansetron for their preventive effects on PONV in patients who underwent gynecologic abdominal surgery with patient-controlled epidural analgesia. This prospective, double-blind, randomized study comprised 44 patients who underwent gynecologic abdominal surgery. They were randomly allocated to receive 150 mg intravenous fosaprepitant (n = 24; NKI group) or 4 mg ondansetron (n = 20; ONS group) before anesthesia, which was maintained with volatile anesthetics, remifentanil, fentanyl, and rocuronium. All patients received postoperative fentanyl by patient-controlled epidural anesthesia. The incidence of nausea and vomiting, complete response rate (i.e., no vomiting and no rescue antiemetic use), rescue antiemetic use, nausea score (0-3), and visual analog scale score (VAS 0-10) for pain were recorded at 2, 24, 48, and 72 h after surgery. No (0 %) patient in the NKI group experienced vomiting after surgery; however, 4-6 (20-30 %) of 20 patients in the ONS group experienced vomiting. This difference was significant at 0-24, 0-48, and 0-72 h. During the study period, no significant differences existed between the NK1 and ONS groups in the incidence of PONV, complete response rate, rescue antiemetic use, nausea score, and VAS score for pain. Compared to ondansetron, fosaprepitant more effectively decreased the incidence of vomiting in patients who underwent gynecologic abdominal surgery with patient-controlled epidural analgesia.

Possible radiation induced cancer of the thoracic esophagus after postoperative irradiation for the breast cancer

International Nuclear Information System (INIS)

Ueda, Mamoru; Matsubara, Toshiki; Kasumi, Fujio; Nishi, Mitsumasa; Kajitani, Tamaki

1991-01-01

We report 11 patients with cancer of the thoracic esophagus developing after postoperative irradiation therapy for breast cancer. Irradiation was done immediately after mastectomy in these patients and the irradiation field included the unilateral or bilateral parasternal region. They received a total dose ranging from 35 Gy to 60 Gy and the dose received to the thoracic esophagus was estimated from 10 Gy to 48 Gy. All cancer sites were involved in the irradiation field. The latent intervals of 10 patients from radiation to the manifest of cancer ranged from 10 to 19 years. Among 4777 women undergoing mastectomy for breast cancer between 1946 and 1980 in our hospital, 8 women (0.17%) developed cancer of the thoracic esophagus, whereas 5 (0.335%) out of 1534 women treated with mastectomy and radiotherapy with Linac between 1964 and 1980 developed cancer of the thoracic esophagus. Higher incidence of esophageal cancer in patients treated with surgery and radiation suggests that these cancers might be induced by radiation. Eight patients had esophagectomy and 4 patients of them received postoperative irradiation. They have survived from 9 months to 13 years. Two patients were controlled well by the irradiation alone. It is interesting that radiation therapy is sensitive to the possible radiation induced cancer of the thoracic esophagus. Follow up study should be directed to the possible development of second malignancy in patients who survive for a long time after radiation therapy. (author)

The Ehrlich Tumor Induces Pain-Like Behavior in Mice: A Novel Model of Cancer Pain for Pathophysiological Studies and Pharmacological Screening

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Cassia Calixto-Campos

2013-01-01

Full Text Available The Ehrlich tumor is a mammary adenocarcinoma of mice that can be developed in solid and ascitic forms depending on its administration in tissues or cavities, respectively. The present study investigates whether the subcutaneous plantar administration of the Ehrlich tumor cells induces pain-like behavior and initial pharmacological susceptibility characteristics. The Ehrlich tumor cells (1 × 104–107 cells induced dose-dependent mechanical hyperalgesia (electronic version of the von Frey filaments, paw edema/tumor growth (caliper, and flinches compared with the saline group between days 2 and 12. There was no difference between doses of cells regarding thermal hyperalgesia in the hot-plate test. Indomethacin (a cyclooxygenase inhibitor and amitriptyline hydrochloride (a tricyclic antidepressant treatments did not affect flinches or thermal and mechanical hyperalgesia. On the other hand, morphine (an opioid inhibited the flinch behavior and the thermal and mechanical hyperalgesia. These effects of morphine on pain-like behavior were prevented by naloxone (an opioid receptor antagonist treatment. None of the treatments affected paw edema/tumor growth. The results showed that, in addition to tumor growth, administration of the Ehrlich tumor cells may represent a novel model for the study of cancer pain, specially the pain that is susceptible to treatment with opioids, but not to cyclooxygenase inhibitor or to tricyclic antidepressant.

Transcutaneous Electrical Nerve Stimulation (TENS) for the Control of Pain during Rehabilitation Following Total Knee Arthroplasty (TKA): A Randomized, Blinded, Placebo-Controlled Trial

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Rakel, Barbara; Zimmerman, M. Bridget; Geasland, Katharine; Embree, Jennie; Clark, Charles R; Noiseux, Nicolas O; Callaghan, John J; Herr, Keela; Walsh, Deirdre; Sluka, Kathleen A

2014-01-01

This study evaluated the efficacy of TENS in reducing pain and hyperalgesia and increasing function following total knee arthroplasty (TKA). We hypothesized participants using TENS during rehabilitation exercises would: 1) report significantly lower pain during range-of-motion (ROM) and fast walking but not at rest; 2) have less hyperalgesia; and, 3) have better function than participants receiving Placebo-TENS or Standard Care. We also hypothesized that change in ROM pain would differ based on psychological characteristics (trait anxiety, pain catastrophizing and depression) and treatment group. This prospective, randomized study used intent-to-treat analyses on 317 subjects after primary, unilateral TKA. Assessors, blinded to treatment allocation, measured pain, function (ROM and gait speed), and hyperalgesia (quantitative sensory tests) postoperatively and 6 weeks after surgery. Analgesic intake, anxiety, depression, and pain catastrophizing were also assessed. TENS participants used it 1–2 times/day at 42 mA (on average) and had less pain postoperatively during active knee extension (p=0.019) and fast walking (p=0.006) than Standard Care participants. TENS and Placebo-TENS were not significantly different. TENS participants who scored low on anxiety and pain catastrophizing had a greater reduction in ROM pain at 6 weeks than those scoring high on these factors (p=0.002 and 0.03). Both TENS and Placebo-TENS participants had less postoperative mechanical hyperalgesia (p=0.03 – 0.01) than Standard Care participants. Supplementing pharmacologic analgesia with TENS during rehabilitation exercises reduces movement pain postoperatively but a placebo influence exists and the effect is gone by 6 weeks. Patients with low anxiety and pain catastrophizing may benefit most from TENS. PMID:25270585

The asleep-awake technique using propofol-remifentanil anaesthesia for awake craniotomy for cerebral tumours

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Olsen, Karsten Skovgaard

2008-01-01

Background and objective: We retrospectively reviewed the first 25 planned cases of awake craniotomies using the 'asleep-awake' technique, an alternative to the often-used 'asleep-awake-asleep' technique. Methods: The patients were anaesthetized using propofol/remifentanil anaesthesia, a laryngeal...... mask and controlled ventilation according to a protocol defined before the start of this series of patients. The patients were awakened before the brain mapping and were kept awake throughout the rest of the procedure allowing for additional mapping and modification of the resection of the turnout...... to obtain a tight laryngeal mask. All of the 23 patients were awake as from when the mapping session began and throughout the rest of the operation. In five cases the resection of the tumour was modified as symptoms emerged. These symptoms all subsided in due course. No case of hypoxia was recorded...

Altered Frequency Distribution in the Electroencephalogram is Correlated to the Analgesic Effect of Remifentanil

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Graversen, Carina; Malver, Lasse P; Kurita, Geana P

2015-01-01

Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp...... distributions were extracted by a continuous wavelet transform and normalized into delta, theta, alpha, beta and gamma bands. Alterations relative to pre-treatment responses were calculated for all channels and used as input to the MVPA. Compared to placebo, remifentanil increased the delta band and decreased...... the theta and alpha band oscillations as a mean over all channels (all p ≤ 0.007). The most discriminative channels in these frequency bands were F1 in delta (83.33%, p = 0.0023) and theta bands (95.24%, p band (80.95%, p = 0.0054). These alterations were correlated...

Induction of anaesthesia with remifentanil after bolus midazolam administration in Landrace/Large White swine

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Zacharioudaki, Argyro; Lelovas, Pavlos; Sergentanis, Theodoros N.

2017-01-01

relaxation, resistance to the laryngoscope, vocal cord position, vocal cord movement and response to intubation. The time required to intubate and necessity for an additional midazolam dose were recorded. Baseline and post-intubation variables were compared with paired t tests, whereas for differences......Objective To investigate an alternative combination for anaesthesia induction in swine. Study design Randomized, ‘blinded’ experimental study. Animals Forty-five Landrace/Large White swine weighing 20.0 ± 1.5 kg. Methods Pulse oximetry, heart rate (HR) and blood pressure were measured after...... = 0.008 and p = 0.032, respectively) between baseline and post-intubation phase; in groups R3 and R4, there were decreases in systolic blood pressure (p = 0.040 and p = 0.019, respectively). In the multivariate analysis, remifentanil dose was not associated with the observed changes in haemodynamic...

Postoperative visual loss due to conversion disorder after spine surgery: a case report

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Dailson Mamede Bezerra

Full Text Available Abstract Background and objective Patients undergoing spinal surgeries may develop postoperative visual loss. We present a case of total bilateral visual loss in a patient who, despite having clinical and surgical risk factors for organic lesion, evolved with visual disturbance due to conversion disorder. Case report A male patient, 39 years old, 71 kg, 1.72 m, ASA I, admitted to undergo fusion and discectomy at L4-L5 and L5-S1. Venoclysis, cardioscopy, oximetry, NIBP; induction with remifentanil, propofol and rocuronium; intubation with ETT (8.0 mm followed by capnography and urinary catheterization for diuresis. Maintenance with full target-controlled intravenous anesthesia. During fixation and laminectomy, the patient developed severe bleeding and hypovolemic shock. After 30 min, hemostasis and hemodynamic stability was achieved with infusion of norepinephrine, volume expansion, and blood products. In the ICU, the patient developed mental confusion, weakness in the limbs, and bilateral visual loss. It was not possible to identify clinical, laboratory or image findings of organic lesion. He evolved with episodes of anxiety, emotional lability, and language impairment; the hypothesis of conversion syndrome with visual component was raised after psychiatric evaluation. The patient had complete resolution of symptoms after visual education and introduction of low doses of antipsychotic, antidepressant, and benzodiazepine. Other symptoms also regressed, and the patient was discharged 12 days after surgery. After 60 days, the patient had no more symptoms. Conclusions Conversion disorders may have different signs and symptoms of non-organic origin,including visual component. It is noteworthy that the occurrence of this type of visual dysfunc-tion in the postoperative period of spinal surgery is a rare event and should be remembered asa differential diagnosis.

[Postoperative visual loss due to conversion disorder after spine surgery: a case report].

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Bezerra, Dailson Mamede; Bezerra, Eglantine Mamede; Silva Junior, Antonio Jorge; Amorim, Marco Aurélio Soares; Miranda, Denismar Borges de

Patients undergoing spinal surgeries may develop postoperative visual loss. We present a case of total bilateral visual loss in a patient who, despite having clinical and surgical risk factors for organic lesion, evolved with visual disturbance due to conversion disorder. A male patient, 39 years old, 71kg, 1.72 m, ASA I, admitted to undergo fusion and discectomy at L4-L5 and L5-S1. Venoclysis, cardioscopy, oximetry, NIBP; induction with remifentanil, propofol and rocuronium; intubation with ETT (8.0mm) followed by capnography and urinary catheterization for diuresis. Maintenance with full target-controlled intravenous anesthesia. During fixation and laminectomy, the patient developed severe bleeding and hypovolemic shock. After 30minutes, hemostasis and hemodynamic stability was achieved with infusion of norepinephrine, volume expansion, and blood products. In the ICU, the patient developed mental confusion, weakness in the limbs, and bilateral visual loss. It was not possible to identify clinical, laboratory or image findings of organic lesion. He evolved with episodes of anxiety, emotional lability, and language impairment; the hypothesis of conversion syndrome with visual component was raised after psychiatric evaluation. The patient had complete resolution of symptoms after visual education and introduction of low doses of antipsychotic, antidepressant, and benzodiazepine. Other symptoms also regressed, and the patient was discharged 12 days after surgery. After 60 days, the patient had no more symptoms. Conversion disorders may have different signs and symptoms of non-organic origin, including visual component. It is noteworthy that the occurrence of this type of visual dysfunction in the postoperative period of spinal surgery is a rare event and should be remembered as a differential diagnosis. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

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Laurence Meyer

Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

Concomitant Migraine and Temporomandibular Disorders are Associated With Higher Heat Pain Hyperalgesia and Cephalic Cutaneous Allodynia.

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Chaves, Thais C; Dach, Fabíola; Florencio, Lidiane L; Carvalho, Gabriela F; Gonçalves, Maria C; Bigal, Marcelo E; Speciali, José G; Bevilaqua-Grossi, Débora

2016-10-01

The aim of this study was to assess differences in the levels of hyperalgesia and cutaneous allodynia (CA) among women with migraine, temporomandibular disorders (TMD), or both. Eighty women participated in the study. Mean ages for the control group, TMD group, migraine group, and migraine+TMD group were 26.15 (95% confidence interval [CI], 28.73 to 23.57), 31.65 (95% CI, 37.82 to 25.48), 35.05 (95% CI, 40.37 to 29.73), and 34.20 (95% CI, 37.99 to 30.41) years, respectively. The 12-item Allodynia Symptom Checklist was administered to assess CA. All participants underwent the Quantitative Sensory Test to determine the cold-pain and heat-pain thresholds. Mechanical pain thresholds were assessed using Semmes-Weinstein monofilaments. One-way analysis of variance and χ tests were used for statistical analysis. Alpha was set at 0.05 level for statistical significance. For all sites evaluated, the mean cold-pain threshold values were significantly lower in the TMD, migraine, and TMD+migraine groups compared with the control group. However, the mean heat-pain threshold values in the extracephalic region were significantly smaller only for the TMD+migraine group compared with the control group (41.94°C; 95% CI, 40.54 to 43.34 vs. 44.79°C; 95% CI, 43.45 to 46.12; P=0.03). Mechanical hyperalgesia in orofacial and neck sites was significantly lower in the TMD and TMD+migraine groups compared with the control group. Mean total 12-item Allodynia Symptom Checklist score in the TMD+migraine group was significantly higher than in the migraine group (9.53; 95% CI, 7.45 to 11.60 vs. 6.95; 95% CI, 5.35 to 8.55; P=0.02). More pronounced levels of hyperalgesia and CA were found in patients with both TMD and migraine. Thus, it is suggested that the concomitant presence of TMD and migraine may be related to intensification of central sensitization.

Preoperative pain mechanisms assessed by cuff algometry are associated with chronic postoperative pain relief after total knee replacement.

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Petersen, Kristian Kjær; Graven-Nielsen, Thomas; Simonsen, Ole; Laursen, Mogens Berg; Arendt-Nielsen, Lars

2016-07-01

Chronic postoperative pain after total knee replacement (TKR) in knee osteoarthritis (KOA) implies clinical challenges. Widespread hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in painful KOA. This exploratory study investigated postoperative pain relief 12 months after TKR in 4 subgroups of patients preoperatively profiled by mechanistic quantitative sensory testing. In 103 patients with KOA, pressure pain detection threshold (PDT) and tolerance thresholds (PTT) were assessed at the lower leg using cuff algometry. Temporal summation of pain was measured as an increase in pain intensity scores during 10 repeated (2 seconds intervals) painful cuff stimuli. Conditioned pain modulation was calculated as the relative increase in PDT during painful conditioning stimulation. The grand averages of TSP and CPM were calculated and values below or above were used for subgrouping: facilitated TSP/impaired CPM (group A, N = 16), facilitated TSP/normal CPM (group B, N = 15), normal TSP/impaired CPM (group C, N = 44), and normal TSP/normal CPM (group D, N = 28). Clinical VAS pain intensity scores were collected before and 12 months after TKR surgery and the pain relief calculated. Less pain relief was found in group A (52.0% ± 14.0% pain relief) than in group B (81.1% ± 3.5%, P = 0.023) and group C (79.6% ± 4.4%, P = 0.007), but not group D (69.4% ± 7.9%, P = 0.087). Low preoperative PDT was associated with a less postoperative pain relief (R = -0.222, P = 0.034), whereas TSP or CPM alone showed no associations with postoperative pain relief. This explorative study indicated that patients with osteoarthritis with facilitated TSP together with impaired CPM are more vulnerable to experience less pain relief after TKR.

Avaliação da concentração expirada de isoflurano em infusão continua de remifentanil em cadelas submetidas a mastectomia

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Suzane Lilian Beier

2015-10-01

Full Text Available Os objetivos deste estudo são a avaliação dos efeitos de duas taxas fixas de infusão continua de remifentanil na concentração expirada de isoflurano (ETiso em cadelas submetidas à mastectomia. Foram utilizadas 18 cadelas, 12+2 anos de idade e pesando 15+5 Kg. Os animais foram distribuídos aleatoriamente em 3 grupos (n=6/grupo e submetidos à mastectomia unilateral devido a neoplasia mamária. Todos os animais foram pré-medicados com morfina (0,5 mg Kg-1 e acepromazina (0,03 mg Kg-1, ambas por via intramuscular (IM. A indução da anestesia foi realizada com propofol (dose-efeito. Os animais foram intubados e conectados a um sistema circular com reinalação de gases. Foi utilizada ventilação com pressão positiva intermitente para manutenção de normocapnia com fluxo de oxigênio de 2 L/min e FiO2 de 100%. A anestesia foi mantida com isoflurano e solução salina (grupo controle [GCON], n=6 ou infusão intravenosa de remifentanil na taxa de 0,15 ?g Kg-1min-1 (REMI 0,15 n=6 ou 0,3 ?g Kg-1min-1 (REMI 0,3 n=6. As variáveis cardiovasculares e a ETiso foram monitoradas antes e a cada 15 minutos após o início da cirurgia. Os dados foram analisados por ANOVA com repetições múltiplas para comparações entre momentos e ANOVA seguida de teste Student Newman Keuls (p£0.05 para comparações entre grupos. A frequência cardíaca foi menor em todos os momentos nos grupos REMI 0,15 e REMI 0,3 em comparação com GCON, sendo que não foram encontradas diferenças estatísticas para essa variável entre os dois grupos com infusão de remifentanil. Adicionalmente, os valores de pressão arterial (PAS, PAM e PAD não apresentaram diferenças entre grupos. Os valores basais (antes da cirurgia de ETiso não apresentaram diferenças entre os 3 grupos. Após o início da cirurgia, a ETiso variou entre 1,37±0,3 e 1,05±0,19 no grupo controle; nos grupos REMI 0,15 e REMI 0,3 a ETiso foi 36,5% e 65,7% menor que no grupo controle (M15. A infusão de

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

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Lanters, Eva A H; Teuwen, Christophe P; Yaksh, Ameeta; Kik, Charles; van der Does, Lisette J M E; Mouws, Elisabeth M J P; Knops, Paul; van Groningen, Nicole J; Hokken, Thijmen; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-10

Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF. Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery ( P =0.159), or between different types of surgery ( P =0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF ( P >0.05). EPoAF was not correlated with LPoAF in patients without a history of AF ( P =0.116), in contrast to patients with AF before surgery ( P <0.001). Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

GluN2B/CaMKII mediates CFA-induced hyperalgesia via HDAC4-modified spinal COX2 transcription.

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Lai, Cheng-Yuan; Hsieh, Ming-Chun; Ho, Yu-Cheng; Chen, Gin-Den; Chou, Dylan; Ruan, Ting; Lee, An-Sheng; Wang, Hsueh-Hsiao; Chau, Yat-Pang; Peng, Hsien-Yu; Lai, Cheng-Hung

2018-06-01

Histone deacetylase 4 (HDAC4), which actively shuttles between the nucleus and cytoplasm, is an attractive candidate for a repressor mechanism in epigenetic modification. However, the potential role of HDAC4-dependent epigenetics in the neural plasticity underlying the development of inflammatory pain has not been well established. By injecting complete Freund's adjuvant (CFA) into the hind-paw of Sprague-Dawley rats (200-250 g), we found animals displayed behavioral hyperalgesia was accompanied with HDAC4 phosphorylation and cytoplasmic redistribution in the dorsal horn neurons. Cytoplasmic HDAC4 retention led to its uncoupling with the COX2 promoter, hence prompting spinal COX2 transcription and expression in the dorsal horn. Moreover, the GluN2B-bearing N-methyl-d-aspartate receptor (GluN2B-NMDAR)/calmodulin-dependent protein kinase II (CaMKII) acted as an upstream cascade to facilitate HDAC4 phosphorylation/redistribution-associated spinal COX2 expression after inflammatory insults. The results of this pilot study demonstrated that the development and/or maintenance of inflammatory pain involved the spinal HDAC4-dependent epigenetic mechanisms. Our findings open up a new avenue for the development of a novel medical strategy for the relief of inflammatory pain. Copyright © 2018 Elsevier Ltd. All rights reserved.

Peripheral nerve blocks versus general anesthesia for total knee replacement in elderly patients on the postoperative quality of recovery

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Liu JL

2014-02-01

Full Text Available JunLe Liu,1,* WeiXiu Yuan,1,* XiaoLin Wang,1,* Colin F Royse,2,3 MaoWei Gong,1 Ying Zhao,1 Hong Zhang1 1Anesthesia and Operation Center, Chinese People's Liberation Army General Hospital and Medical School of Chinese People's Liberation Army, Beijing, People's Republic of China; 2Anesthesia and Pain Management Unit, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia; 3Department of Anesthesia and Pain Management, The Royal Melbourne Hospital, Melbourne, Victoria, Australia *These authors contributed equally to this work Background: Both peripheral nerve blocks with sedation or general anesthesia can be used for total knee replacement surgery. Objectives: We compared these anesthetic techniques on the postoperative quality of recovery early in elderly patients. Materials and methods: In our study, 213 patients who were ≥65 years old and undergoing total knee replacement were randomized to peripheral nerve blocks (PNBs – lumbar plexus and sciatic – with propofol sedation, or general anesthesia with combined propofol and remifentanil. Blocks were performed using nerve stimulation and 0.35% ropivacaine. All patients received postoperative multimodal analgesia. Postoperative recovery was assessed at 15 minutes, 40 minutes, 1 day, 3 days, and 7 days after surgery, with the Postoperative Quality of Recovery Scale, in physiological, nociceptive, emotive, modified activities of daily living, modified cognitive, and overall patient perspective domains. Results: Intraoperative blood pressure and heart rate were more stable with PNBs (P<0.001. The recovery was better with PNBs in physiological (P<0.001, emotive (depression and anxiety (P<0.001, nociceptive (pain and nausea (P<0.001, modified cognitive (P<0.001, and all domains recovery (P<0.001, but not in activities of daily living (P=0.181. Intraoperative drugs and the postoperative sulfentanil requirement of the PNBs group were lower (all P<0.001. Differences were

Fatal postoperative systemic pulmonary hypertension in benfluorex-induced valvular heart disease surgery: A case report.

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Baufreton, Christophe; Bruneval, Patrick; Rousselet, Marie-Christine; Ennezat, Pierre-Vladimir; Fouquet, Olivier; Giraud, Raphael; Banfi, Carlo

2017-01-01

Drug-induced valvular heart disease (DI-VHD) remains an under-recognized entity. This report describes a heart valve replacement which was complicated by intractable systemic pulmonary arterial hypertension in a 61-year-old female with severe restrictive mitral and aortic disease. The diagnosis of valvular disease was preceded by a history of unexplained respiratory distress. The patient had been exposed to benfluorex for 6.5 years. The diagnostic procedure documented specific drug-induced valvular fibrosis. Surgical mitral and aortic valve replacement was performed. Heart valve replacement was postoperatively complicated by unanticipated disproportionate pulmonary hypertension. This issue was fatal despite intensive care including prolonged extracorporeal life support. Benfluorex is a fenfluramine derivative which has been marketed between 1976 and 2009. Although norfenfluramine is the common active and toxic metabolite of all fenfluramine derivatives, the valvular and pulmonary arterial toxicity of benfluorex was much less known than that of fenfluramine and dexfenfluramine. The vast majority of benfluorex-induced valvular heart disease remains misdiagnosed as hypothetical rheumatic fever due to similarities between both etiologies. Better recognition of DI-VHD is likely to improve patient outcome.

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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Alireza Abed

2017-11-01

Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

A Costly Lesson: Fatal Respiratory Depression Induced by Clindamycin during Postoperative Patient Controlled Analgesia.

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Wu, Gao; Wu, Guo; Wu, Hanbin

2015-01-01

Many drugs can cause neuromuscular blockade. Clindamycin-related neuromuscular blockade is commonly reported, but fatal clindamycin-induced neuromuscular blockade is rarely reported. We describe a 47-year-old woman who initially presented with endometrial carcinoma. She underwent a laparoscopic-assisted vaginal hysterectomy (LAVH) and bilateral adnexectomy under general anesthesia, secondary to antibiotic treatment with clindamycin 1.2g in 250 mL for about 30 minutes through the peripheral intravenous route during postoperative patient controlled analgesia (PCA). She became unconscious near the end of the infusion, then, despite resuscitation attempts, she died. Clindamycin appeared to have triggered delayed respiratory depression during PCA. A combination of clindamycin and fentanyl led to her respiratory depression in the fatal case.

Genome-wide transcriptional profiling of skin and dorsal root ganglia after ultraviolet-B-induced inflammation.

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John M Dawes

Full Text Available Ultraviolet-B (UVB-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24, chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5, the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022. In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.

Lipopolysaccharide-induced Pulpitis Up-regulates TRPV1 in Trigeminal Ganglia

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Chung, M.-K.; Lee, J.; Duraes, G.; Ro, J.Y.

2011-01-01

Tooth pain often accompanies pulpitis. Accumulation of lipopolysaccharides (LPS), a product of Gram-negative bacteria, is associated with painful clinical symptoms. However, the mechanisms underlying LPS-induced tooth pain are not clearly understood. TRPV1 is a capsaicin- and heat-gated nociceptive ion channel implicated in thermosensation and hyperalgesia under inflammation or injury. Although TRPV1 is expressed in pulpal afferents, it is not known whether the application of LPS to teeth modulates TRPV1 in trigeminal nociceptors. By assessing the levels of protein and transcript of TRPV1 in mouse trigeminal ganglia, we demonstrate that dentinal application of LPS increases the expression of TRPV1. Our results suggest that the up-regulation of TRPV1 in trigeminal nociceptors following bacterial infection could contribute to hyperalgesia under pulpitis conditions. PMID:21712529

Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

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Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

2005-01-01

To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil

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Prontera A

2017-03-01

Full Text Available Andrea Prontera,1 Stefano Baroni,2 Andrea Marudi,2 Franco Valzania,3 Alberto Feletti,1 Francesca Benuzzi,4 Elisabetta Bertellini,2 Giacomo Pavesi1 1Department of Neurosurgery, Nuovo Ospedale Civile SAgostino-Estense, 2Department of Anesthesiology, Nuovo Ospedale Civile SAgostino-Estense, 3Department of Neurology, Nuovo Ospedale Civile S Agostino-Estense, 4Department of Neuroscience, University of Modena and Reggio Emilia, Modena, Italy Introduction: Awake craniotomy allows continuous monitoring of patients’ neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic–sedative medication is increasing.Methods: Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management.Results: The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure.Conclusion: In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used. Keywords: dexmedetomidine, awake surgery, anesthesia

Anestesia venosa total com infusão alvo-controlada de remifentanil e propofol para ablação de fibrilação atrial Anestesia venosa total con infusión objeto-controlada de remifentanil y propofol para ablación de la fibrilación atrial Total intravenous anesthesia with target-controlled infusion of remifetanil and propofol for ablation of atrial fibrillation

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Fernando Squeff Nora

2009-12-01

Full Text Available JUSTIFICATIVA E OBJETIVOS: A ablação de fibrilação atrial (FA é um procedimento novo em nosso meio, embora seja comum em outros centros. A escolha da anestesia, monitores e cuidados anestesiológicos para esse procedimento, realizado fora do bloco cirúrgico, não tem sido descrita. O objetivo deste relato foi descrever uma técnica de anestesia para a realização de ablação de FA. RELATO DO CASO: Paciente feminina, 49 anos, 73 kg, 155 cm, ASA II por hipertensão arterial sistêmica. A monitorização constou de eletrocardiograma com 12 derivações, oximetria de pulso, frequência cardíaca, eletroencefalografia bispectral para medidas de BIS, taxa de supressão (SR e SEF95 e pressão arterial média (PAM. A indução anestésica foi realizada com propofol por via venosa, em infusão alvo-controlada (IAC, com alvo regulado em 4 µg.mL-1, remifentanil por via venosa, em IAC, com alvo de 3 ng.mL¹, e rocurônio por via venosa em bolus na dose de 0,2 mg.kg-1. O modelo farmacocinético de propofol utilizado foi o descrito por Marsh e incorporado à bomba de propofol PFS®. O modelo farmacocinético de remifentanil utilizado foi o descrito por Minto e incorporado à bomba de infusão Alaris PK®. As concentrações, no local efetor ou biofase, corresponderam às informações obtidas através das bombas de infusão e representaram medidas preditivas das concentrações de ambos os fármacos nos respectivos locais de ação. As concentrações de propofol e de remifentanil foram reguladas de acordo com o BIS e a PAM, respectivamente. CONCLUSÕES: A anestesia venosa total para ablação de FA pode ser uma opção segura, levando-se em conta que não há alteração da eletrofisiologia das vias acessórias. A literatura é escassa a este respeito e novas publicações poderão ou não justificar esta modalidade de anestesia durante ablação de FA.JUSTIFICATIVA Y OBJETIVOS: La ablación de fibrilación atrial (FA es un procedimiento nuevo en

Do Australian Football players have sensitive groins? Players with current groin pain exhibit mechanical hyperalgesia of the adductor tendon.

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Drew, Michael K; Lovell, Gregory; Palsson, Thorvaldur S; Chiarelli, Pauline E; Osmotherly, Peter G

2016-10-01

This is the first study to evaluate the mechanical sensitivity, clinical classifications and prevalence of groin pain in Australian football players. Case-control. Professional (n=66) and semi-professional (n=9) Australian football players with and without current or previous groin injuries were recruited. Diagnoses were mapped to the Doha Agreement taxonomy. Point and career prevalence of groin pain was calculated. Pressure pain thresholds (PPTs) were assessed at regional and distant sites using handheld pressure algometry across four sites bilaterally (adductor longus tendon, pubic bone, rectus femoris, tibialis anterior muscle). To assess the relationship between current groin pain and fixed effects of hyperalgesia of each site and a history of groin pain, a mixed-effect logistic regression model was utilised. Receiver Operator Characteristic (ROC) curve were determined for the model. Point prevalence of groin pain in the preseason was 21.9% with a career prevalence of 44.8%. Adductor-related groin pain was the most prevalent classification in the pre-season period. Hyperalgesia was observed in the adductor longus tendon site in athletes with current groin pain (OR=16.27, 95% CI 1.86 to 142.02). The ROC area under the curve of the regression model was fair (AUC=0.76, 95% CI 0.54 to 0.83). Prevalence data indicates that groin pain is a larger issue than published incidence rates imply. Adductor-related groin pain is the most common diagnosis in pre-season in this population. This study has shown that hyperalgesia exists in Australian football players experiencing groin pain indicating the value of assessing mechanical pain sensitivity as a component of the clinical assessment. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Involvement of spinal glutamate transporter-1 in the development of mechanical allodynia and hyperalgesia associated with type 2 diabetes

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Shi J

2016-11-01

Full Text Available Jinshan Shi,1,* Ke Jiang,2,* Zhaoduan Li,3 1Department of Anesthesiology, Guizhou Provincial People’s Hospital, 2Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 3Department of Anesthesiology, Tianjin Nankai Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Little is known about the effects of the development of type 2 diabetes on glutamate homeostasis in the spinal cord. Therefore, we quantified the extracellular levels of glutamate in the spinal cord of Zucker diabetic fatty (ZDF rats using in vivo microdialysis. In addition, protein levels of glutamate transporter-1 (GLT-1 in the spinal cord of ZDF rats were measured using Western blot. Finally, the effects of repeated intrathecal injections of ceftriaxone, which was previously shown to enhance GLT-1 expression, on the development of mechanical allodynia and hyperalgesia as well as on basal extracellular level of glutamate and the expression of GLT-1 in the spinal cord of ZDF rats were evaluated. It was found that ZDF rats developed mechanical hyperalgesia and allodynia, which were associated with increased basal extracellular levels of glutamate and attenuated levels of GLT-1 expression in the spinal cord, particularly in the dorsal horn. Furthermore, repeated intrathecal administrations of ceftriaxone dose-dependently prevented the development of mechanical hyperalgesia and allodynia in ZDF rats, which were correlated with enhanced GLT-1 expression without altering the basal glutamate levels in the spinal cord of ZDF rats. Overall, the results suggested that impaired glutamate reuptake in the spinal cord may contribute to the development of neuropathic pains in type 2 diabetes. Keywords: diabetes, peripheral neuropathy, spinal cord, Zucker diabetic fatty rats, glutamate, glutamate transporter-1

Postoperative pain

DEFF Research Database (Denmark)

Kehlet, H; Dahl, J B

1993-01-01

also modify various aspects of the surgical stress response, and nociceptive blockade by regional anesthetic techniques has been demonstrated to improve various parameters of postoperative outcome. It is therefore stressed that effective control of postoperative pain, combined with a high degree......Treatment of postoperative pain has not received sufficient attention by the surgical profession. Recent developments concerned with acute pain physiology and improved techniques for postoperative pain relief should result in more satisfactory treatment of postoperative pain. Such pain relief may...

Clonidine or remifentanil for adequate surgical conditions in patients undergoing endoscopic sinus surgery: a randomized study

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Laurent Bairy

2017-05-01

Full Text Available Background Deliberate hypotension is one way to achieve a bloodless surgical field in endoscopic sinus surgery (ESS. We compared two anaesthesia regimens to induce deliberate hypotension and attempted to determine the most efficient one. Methods Fifty-nine patients undergoing ESS were minimized into two groups. In the CLO group, patients received I.V. sufentanil 0.15 µg/kg together with I.V. clonidine 2–3 µg/kg. In the REMI group, patients received remifentanil at a rate of up to 1 µg/kg/min. Fromme scores were collected 15 min after the incision and at the end of the procedure. Mean arterial pressure readings (MAP, heart rate readings, time to eyes opening, time to extubation, pain scores, analgesic requirements, and oxygen needs were collected and compared. Results There were no significant differences in Fromme scores between the two groups. The averaged MAP from 15 min to the end of the procedure was significantly lower in the REMI group; these patients also received more ephedrine. Significantly fewer patients in the CLO group needed oxygen therapy to keep their Pulse Oximeter Oxygen Saturation within 3% of their preoperative values. Patients in this group also needed less piritramide in the recovery room, and their pain scores were lower at discharge from the recovery room. Discussion Although both anaesthesia regimens offered a similar quality of surgical field, this study suggests that clonidine had a better average safety profile. Furthermore, patients who received this regimen required fewer painkillers immediately after surgery.

Epidural morphine for postoperative pain relief in children

DEFF Research Database (Denmark)

Henneberg, S W; Hole, P; Haas, Inge Madsen De

1993-01-01

Epidural morphine for postoperative pain relief is in general use, and has proved to be very efficient in adults. The epidural technique and the use of epidural morphine are much less frequent in children. For 2 years we have prospectively followed 76 children who had epidural morphine...... for postoperative pain relief after major abdominal surgery. The age distribution was from newborn to 13 years, with a median age of 12 months. It was estimated that 94% of the patients had good analgesia for the first 24 postoperative hours and no other opioids were given. The side effects were few, but one case...... the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

Anti-hyperalgesic and anti-inflammatory effects of long termcalcium administrationduring adjuvant-induced arthritisin rats

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Setareh Khashaee

2015-12-01

Full Text Available Introduction: Inflammation and edema Symptoms are physiological response to triggers that can be induced by different mediators such as cytokines. Rheumatoid arthritis is the most common form of arthritis which is characterized by chronic inflammation of the synovial membrane, severe and debilitating pain and progressive cartilage injury. It is clear that cytokines are involved in different stages of inflammation by inducing pro-inflammatory effects; TNF-α as a cytokine involved in the pathogenesis of rheumatoid arthritis. In this study we attempted to investigate the role of prescription of calcium to reduce inflammatory edema and serum TNF-α level during different stages of arthritic inflammation induced by Complete Freund Adjuvant (CFA injection in male Wistar rats.Methods:In this Applicable-Fundamental study, we used male Wistar rats and adjuvant arthritis was created by once subcutaneous injection of CFA in the right hindpaw of animals on day zero in experimental groups. Various doses of calcium were prepared and injected within 21 days of study. Hyperalgesia and paw volume changes wereassessed byradiant heat andplethysmometer over several days, respectively. The serum levels of TNF-α were studied by ELISA standard kit of rat during various phases and were measured according to the kit.Results:The results indicated dose related effects of long term calcium administration on edema, hyperalgesia and serum TNF-α level reduction. Daily treatment with effective dose of calcium (5 mg/kg in AA+ Ca group significantly decreased paw edema, hyperalgesia and serum TNF-α level incomparison to AA and AA+ Vehicle groups on days 7, 14 and 21 of study.Conclusions:Findings of this study showed;long term administration of calcium in the proper dosage can act as an anti-inflammatory agent and pain modulator during adjuvant-induced arthritis and a part of those effects may conducted by decreasing of serum TNF-α level.

Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

OpenAIRE

Flatters, Sarah J.L.; Bennett, Gary J.

2006-01-01

Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.

Science.gov (United States)

Tian, Jie; Gu, Yiwen; Su, Diansan; Wu, Yichao; Wang, Xiangrui

2009-02-01

The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

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Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G

2013-06-01

There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

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Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

2013-01-01

Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random or...

Duration and distribution of experimental muscular hyperalgesia in humans following combined infusions of serotonin and bradykinin

DEFF Research Database (Denmark)

Babenko, Victor; Svensson, Peter; Graven-Nielsen, Thomas

2000-01-01

-infusions interval of 3 min. Infusions of isotonic saline (NaCl, 0.9%) were given as control. Pain intensity was continuously scored on a visual analogue scale (VAS), and subjects drew the distribution of the pain areas on an anatomical map. Pressure pain thresholds (PPTs) were assessed with an electronic algometer....... In addition, PPTs were significantly decreased (Peffect of bradykinin in producing experimental muscle pain and muscle hyperalgesia to mechanical stimuli. The combination of serotonin and bradykinin can produce muscle...

Exopolysaccharide Produced by Probiotic Strain Lactobacillus paraplantarum BGCG11 Reduces Inflammatory Hyperalgesia in Rats

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Miroslav Dinić

2018-01-01

Full Text Available The aim of this study was to test the potential of high molecular weight exopolysaccharide (EPS produced by the putative probiotic strain Lactobacillus paraplantarum BGCG11 (EPS CG11 to alleviate inflammatory pain in Wistar rats. The EPS CG11 was isolated from bacterial surface and was subjected to Fourier-transform infrared spectroscopy (FTIR and thermal analysis. FTIR spectra confirmed the polysaccharide structure of isolated sample, while the thermal methods revealed good thermal properties of the polymer. The antihyperalgesic and antiedematous effects of the EPS CG11 were examined in the rat model of inflammation induced by carrageenan injection in hind paw. The results showed that the intraperitoneal administration of EPS CG11 produced a significant decrease in pain sensations (mechanical hyperalgesia and a paw swelling in a dose-dependent manner as it was measured using Von Frey anesthesiometer and plethysmometer, respectively. These effects were followed by a decreased expression of IL-1β and iNOS mRNAs in rat’s paw tissue suggesting that the antihyperalgesic and antiedematous effects of the EPS CG11 are related to the suppression of inflammatory response. Additionally, we demonstrated that EPS CG11 exhibits immunosuppressive properties in the peritonitis model induced by carrageenan. Expression levels of pro-inflammatory mediators IL-1β, TNF-α and iNOS were decreased, together with the enhanced secretion of anti-inflammatory IL-10 and IL-6 cytokines, while neutrophil infiltration was not changed. To the best of our knowledge, this is the first study which reports an antihyperalgesic effect as the novel property of bacterial EPSs. Given the high demands of pharmaceutical industry for the replacement of commonly used analgesics due to numerous side effects, this study describes a promising natural compound for the future pharmacological testing in the area.

Monocytes/Macrophages Control Resolution of Transient Inflammatory Pain

Science.gov (United States)

Willemen, Hanneke L. D. M.; Eijkelkamp, Niels; Carbajal, Anibal Garza; Wang, Huijing; Mack, Matthias; Zijlstra, Jitske; Heijnen, Cobi J.; Kavelaars, Annemieke

2014-01-01

Insights into mechanisms governing resolution of inflammatory pain are of great importance for many chronic pain–associated diseases. Here we investigate the role of macrophages/monocytes and the anti-inflammatory cytokine interleukin-10 (IL-10) in the resolution of transient inflammatory pain. Depletion of mice from peripheral monocytes/macrophages delayed resolution of intraplantar IL-1β- and carrageenan-induced inflammatory hyperalgesia from 1 to 3 days to >1 week. Intrathecal administration of a neutralizing IL-10 antibody also markedly delayed resolution of IL-1β- and carrageenan-induced inflammatory hyperalgesia. Recently, we showed that IL-1β- and carrageenan-induced hyperalgesia is significantly prolonged in LysM-GRK2+/− mice, which have reduced levels of G-protein-coupled receptor kinase 2 (GRK2) in LysM+ myeloid cells. Here we show that adoptive transfer of wild-type, but not of GRK2+/−, bone marrow-derived monocytes normalizes the resolution of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Adoptive transfer of IL-10−/− bone marrow-derived monocytes failed to normalize the duration of IL-1β-induced hyperalgesia in LysM-GRK2+/− mice. Mechanistically, we show that GRK2+/− macrophages produce less IL-10 in vitro. In addition, intrathecal IL-10 administration attenuated IL-1β-induced hyperalgesia in LysM-GRK2+/− mice, whereas it had no effect in wild-type mice. Our data uncover a key role for monocytes/macrophages in promoting resolution of inflammatory hyperalgesia via a mechanism dependent on IL-10 signaling in dorsal root ganglia. Perspective We show that IL-10-producing monocytes/macrophages promote resolution of transient inflammatory hyperalgesia. Additionally, we show that reduced monocyte/macrophage GRK2 impairs resolution of hyperalgesia and reduces IL-10 production. We propose that low GRK2 expression and/or impaired IL-10 production by monocytes/macrophages represent peripheral biomarkers for the risk of developing

Perioperative ischaemia-induced liver injury and protection strategies: An expanding horizon for anaesthesiologists

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Chandra Kant Pandey

2013-01-01

Full Text Available Liver resection is an effective modality of treatment in patients with primary liver tumour, metastases from colorectal cancers and selected benign hepatic diseases. Its aim is to resect the grossly visible tumour with clear margins and to ensure that the remnant liver mass has sufficient function which is adequate for survival. With the advent of better preoperative imaging, surgical techniques and perioperative management, there is an improvement in the outcome with decreased mortality. This decline in postoperative mortality after hepatic resection has encouraged surgeons for more radical liver resections, leaving behind smaller liver remnants in a bid to achieve curative surgeries. But despite advances in diagnostic, imaging and surgical techniques, postoperative liver dysfunction of varied severity including death due to liver failure is still a serious problem in such patients. Different surgical and non-surgical techniques like reducing perioperative blood loss and consequent decreased transfusions, vascular occlusion techniques (intermittent portal triad clamping and ischaemic preconditioning, administration of pharmacological agents (dextrose, intraoperative use of methylprednisolone, trimetazidine, ulinastatin and lignocaine and inhaled anaesthetic agents (sevoflurane and opioids (remifentanil have demonstrated the potential benefit and minimised the adverse effects of surgery. In this article, the authors reviewed the surgical and non-surgical measures that could be adopted to minimise the risk of postoperative liver failure following liver surgeries with special emphasis on ischaemic and pharmacological preconditioning which can be easily adapted clinically.

Experimental knee pain evoke spreading hyperalgesia and facilitated temporal summation of pain

DEFF Research Database (Denmark)

Jørgensen, Tanja Schjødt; Henriksen, Marius; Danneskiold-Samsøe, Bente

2013-01-01

OBJECTIVES: This study evaluated the deep-tissue pressure pain sensitivity and temporal summation of pain within and around healthy knees exposed to experimental pain. DESIGN: The study was designed as a randomized crossover trial, with each subject tested on 1 day. SETTING: All tests were carried...... occasions: baseline, immediately after the injection, and when pain had vanished. Assessments sites were located in the peripatellar region, vastus lateralis, and tibialis anterior muscles. RESULTS: The experimental knee pain model demonstrated 1) hyperalgesia to pressure stimulation on the infrapatellar...... fat pad during experimental pain, and 2) facilitated temporal summation of pressure pain at the infrapatellar fat pad and knee-related muscles. CONCLUSION: The increased sensitivity and temporal summation found in this study were exclusive to deep -tissue with no contralateral decreased pain...

[Expressions of neuropathic pain-related proteins in the spinal cord dorsal horn in rats with bilateral chronic constriction injury].

Science.gov (United States)

Shen, Le; Li, Xu; Wang, Hai-tang; Yu, Xue-rong; Huang, Yu-guang

2013-12-01

To evaluate the pain-related behavioral changes in rats with bilateral chronic constriction injury(bCCI)and identify the expressions of neuropathic pain-related proteins. The bCCI models were established by ligating the sciatic nerves in female Sprague Dawley rats. Both mechanical hyperalgesia and cold hyperalgesia were evaluated through electronic von Frey and acetone method. Liquid chromatography-mass spectrometry/mass spectrometry was applied to characterize the differentially expressed proteins. Both mechanical withdrawal threshold and cold hyperalgesia threshold decreased significantly on the postoperative day 7 and 14, when compared with na ve or sham rats(P <0.05). Twenty five differentially expressed proteins associated with bilateral CCI were discovered, with eighteen of them were upregulated and seven of them downregulated. The bCCT rats have remarkably decreased mechanical and cold hyperalgesia thresholds. Twenty five neuropathic pain-related proteins are found in the spinal cord dorsal horn.

[Perioperative management of a child with central diabetes insipidus who underwent two surgeries before and after desmopressin administration].

Science.gov (United States)

Kiriyama, Keiji; Tachibana, Kazuya; Nishimura, Nobuyuki; Takeuchi, Muneyuki; Kinouchi, Keiko

2013-03-01

A 14-year-old girl weighing 32 kg was diagnosed with suprasellar tumor causing hydrocephalus, hypothyroidism, adrenal dysfunction and central diabetes insipidus. She was treated with levothyroxine and hydrocortisone and urged to take fluid to replace urine. She was scheduled to undergo ventricular drainage to relieve hydrocephalus prior to tumor resection. For the first surgery, desmopressin was not started and urine output reached 4,000 to 6,000 ml x day(-1), urine osmolality 64 mOsm x l(-1) and urine specific gravity 1.002. Anesthesia was induced with sevoflurane and maintained with propofol and remifentanil. Maintenance fluid was with acetated Ringer's solution and urine loss was replaced with 5% dextrose. Bradycardia and hypotension occurred after intubation, which was treated with volume load. Infusion volume was 750 ml and urine output was 1100 ml during 133 min of anesthesia. Postoperative day 1 nasal desmopressin was started. Ten days later, partial tumor resection was performed. Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane and remifentanil. Infusion volume was 610 ml, urine output 380 ml, and blood loss 151 ml during 344 min of anesthesia. Hemodynamic parameters were stable throughout the procedure. Pathology of the tumor was revealed to be germinoma. Bradycardia and hypotension experienced during the first surgery was suspected to be caused by preoperative hypovolemia brought by polyuria. Desmopressin was proved to be effective to treat excessive urine output and to maintain good perioperative water balance.

Postoperative radiation therapy for adenoid cystic carcinoma

International Nuclear Information System (INIS)

Oguchi, Masahiko; Shikama, Naoto; Gomi, Koutarou; Shinoda, Atsunori; Nishikawa, Atsushi; Arakawa, Kazukiyo; Sasaki, Shigeru; Takei, Kazuyoshi; Sone, Syusuke

2000-01-01

The authors retrospectively assessed the usefulness of postoperative radiation therapy after local resection of adenoid cystic carcinoma, with emphasis on organ-conserving treatment and the cosmetic results. Between 1985 and 1995, 32 patients underwent local resection followed by postoperative radiation therapy with curative and organ-conserving intent. None of patients received any form of chemotherapy as part of their initial treatment. Radiation therapy was carried out by techniques that were appropriate for the site and extension of each tumor. The 5-year local control, disease-free, and overall survival rates of all patients were 76%, 68%, and 86%, respectively. The 5-year local control rate and disease-free survival rate of patients with microscopically positive margins were 89% and 75%, respectively, and higher than in patients with macroscopically residual disease, but no significant difference in 5-year overall survival rate was observed. The postoperative cosmetic results in 29 patients with head and neck lesions were evaluated. No difference was documented between the cosmetic results postoperatively setting and after postoperative radiotherapy, and no significant differences in cosmetic results were observed according to radiation dose. The combination of local resection with organ-conserving intent and postoperative radiation therapy provided good cosmetic results in patients with T1 or T2 lesions. Postoperative radiation therapy with smaller fractions is useful, because good local control can be achieved in patients with adenoid cystic carcinoma having microscopically positive margins without inducing any late adverse reactions. However, the number of patients was too small and the follow-up period was too short to draw any definite conclusion in regard to fraction size. A much longer follow-up study with a larger number patients will be required to accurately determine the optimal treatment intensity and duration of treatment. (K.H.)

Postoperative spinal column; Postoperative Wirbelsaeule

Energy Technology Data Exchange (ETDEWEB)

Kaefer, W. [Westpfalzklinikum GmbH, Standort II, Abteilung fuer Wirbelsaeulenchirurgie, Kusel (Germany); Heumueller, I. [Westpfalzklinikum GmbH, Standort II, Institut fuer Radiologie II, Kusel (Germany); Harsch, N.; Kraus, C.; Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

2016-08-15

As a rule, postoperative imaging is carried out after spinal interventions to document the exact position of the implant material. Imaging is absolutely necessary when new clinical symptoms occur postoperatively. In this case a rebleeding or an incorrect implant position abutting a root or the spinal cord must be proven. In addition to these immediately occurring postoperative clinical symptoms, there are a number of complications that can occur several days, weeks or even months later. These include the failed back surgery syndrome, implant loosening or breakage of the material and relapse of a disc herniation and spondylodiscitis. In addition to knowledge of the original clinical symptoms, it is also important to know the operation details, such as the access route and the material used. In almost all postoperative cases, imaging with contrast medium administration and corresponding correction of artefacts by the implant material, such as the dual energy technique, correction algorithms and the use of special magnetic resonance (MR) sequences are necessary. In order to correctly assess the postoperative imaging, knowledge of the surgical procedure and the previous clinical symptoms are mandatory besides special computed tomography (CT) techniques and MR sequences. (orig.) [German] In der Regel erfolgt bei spinalen Eingriffen eine postoperative Bildgebung, um die exakte Lage des Implantatmaterials zu dokumentieren. Unbedingt notwendig ist die Bildgebung, wenn postoperativ neue klinische Symptome aufgetreten sind. Hier muessen eine Nachblutung bzw. inkorrekte, eine Wurzel oder das Myelon tangierende Implantatlage nachgewiesen werden. Neben diesen direkt postoperativ auftretenden klinischen Symptomen gibt es eine Reihe von Komplikationen, die erst nach mehreren Tagen, Wochen oder sogar nach Monaten auftreten koennen. Hierzu zaehlen das Failed-back-surgery-Syndrom, die Implantatlockerung oder -bruch, aber auch ein Rezidivvorfall und die Spondylodiszitis. Neben der

Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

Science.gov (United States)

Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

2012-01-01

Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

The Relationship between Mechanical Hyperalgesia Assessed by Manual Tender Point Examination and Disease Severity in Patients with Chronic Widespread Pain: A Cross-Sectional Study

DEFF Research Database (Denmark)

Amris, Kirstine; Wæhrens, Eva Ejlersen; Jespersen, Anders

2014-01-01

The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity...

Role of ventrolateral orbital cortex muscarinic and nicotinic receptors in modulation of capsaicin-induced orofacial pain-related behaviors in rats.

Science.gov (United States)

Tamaddonfard, Esmaeal; Erfanparast, Amir; Abbas Farshid, Amir; Delkhosh-Kasmaie, Fatmeh

2017-11-15

Acetylcholine, as a major neurotransmitter, mediates many brain functions such as pain. This study was aimed to investigate the effects of microinjection of muscarinic and nicotinic acetylcholine receptor antagonists and agonists into the ventrolateral orbital cortex (VLOC) on capsaicin-induced orofacial nociception and subsequent hyperalgesia. The right side of VLOC was surgically implanted with a guide cannula in anaesthetized rats. Orofacial pain-related behaviors were induced by subcutaneous injection of a capsaicin solution (1.5µg/20µl) into the left vibrissa pad. The time spent face rubbing with ipsilateral forepaw and general behavior were recorded for 10min, and then mechanical hyperalgesia was determined using von Frey filaments at 15, 30, 45 and 60min post-capsaicin injection. Alone intra-VLOC microinjection of atropine (a muscarinic acetylcholine receptor antagonist) and mecamylamine (a nicotinic acetylcholine receptor antagonist) at a similar dose of 200ng/site did not alter nocifensive behavior and hyperalgesia. Microinjection of oxotremorine (a muscarinic acetylcholine receptor agonist) at doses of 50 and 100ng/site and epibatidine (a nicotinic acetylcholine receptor agonist) at doses of 12.5, 25, 50 and 100ng/site into the VLOC suppressed pain-related behaviors. Prior microinjections of 200ng/site atropine and mecamylamine (200ng/site) prevented oxotremorine (100ng/site)-, and epibatidine (100ng/site)-induced antinociception, respectively. None of the above-mentioned chemicals changed general behavior. These results showed that the VLOC muscarinic and nicotinic acetylcholine receptors might be involved in modulation of orofacial nociception and hypersensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of Postoperative Pain between Infiltrative Local Anesthesia plus Paracetamol and Total Intravenous Anesthesia plus Paracetamol in Ambulatory Breast Surgery

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Kasra Karvandian

2015-08-01

Full Text Available Background: Acute postoperative pain is an important surgical side effect that may delay patient discharge in ambulatory operations; moreover, the strategies used to alleviate pain may cause side effects that require longer hospitalization to recover. In this clinical trial, we compared two current anesthetic methods with special concerns about postoperative pain intensity beside other important components of ambulatory anesthesia.Methods: This clinical trial was conducted on two age-matched groups of 75 members who underwent ambulatory breast surgery. Patients in the first group (GA underwent general anesthesia with propofol plus remifentanil by employing a laryngeal mask airway. In the second group (LA, the surgeon used infiltration of 2% lidocaine in the breast tissue and midazolam was applied as premedication. At the end of surgery, paracetamol was administered to all patients in both groups. The pain score was evaluated when the patients were fully awake using a numerical pain rating scale. Patients with severe pain received analgesia. The length of postanesthesia care unit (PACU stay was recorded for each patient.Results: None of the patients in the LA group were satisfied because of the experience of needle insertion into their breast tissue (P = 0.001. The patients in the LA group experienced more pain in PACU requiring adjuvant analgesia (P = 0.001. Patients in the LA group had longer PACU admission (P = 0.001.Conclusions: Patients in the LA group had higher pain scores and were dissatisfied with the plan of their anesthesia. This may confirm the role of preemptive analgesia or the effect of emotional stress of breast tissue needling in wakeful patient.

Pharmacological inhibition of eicosanoid synthesis and hyperalgesia in yeast-injected rat paws

International Nuclear Information System (INIS)

Opas, E.E.; Dallob, A.; Herold, E.; Luell, S.; Humes, J.L.

1986-01-01

Brewer's yeast caused an inflammation characterized by edema and hyperalgesia when injected into the hindpaw of a rat. These events were temporally distinct and each was associated with increases of specific arachidonic and oxygenation products. As determined by radioimmunoassay (RIA) on whole paw lipid extracts, the 5-lipoxygenase (5-LO) products, leukotrienes C 4 and D 4 and 5-hydroxyeicosatetraendic acid (5-HETE) were synthesized concurrently with the onset of edema (maximal at 15 minutes after yeast injection). The hyperalgesic phase of the inflammation (3-4 hr after yeast injection) was associated with increased tissue levels of the cyclooxygenase (CO) products, prostaglandin E 2 and thromboxane B 2 (TXB 2 ) as well as increases in levels of the 5-LO products, leukotriene B 4 (LTB 4 ) and 5-HETE. Pharmacological agents modulated the synthesis of eicosanoids and suppressed the hyperalgesic response

Postoperative cognitive dysfunction : Involvement of neuroinflammation and neuronal functioning

NARCIS (Netherlands)

Hovens, Iris B.; Schoemaker, Regien G.; van der Zee, Eddy A.; Absalom, Anthony R.; Heineman, Erik; van Leeuwen, Barbara L.

Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced inflammatory processes, which may influence neuronal functioning either directly or through modulation of intraneuronal pathways, such as the brain derived neurotrophic factor (BDNF) mediated pathway.

Clinically suspected anaphylaxis induced by sugammadex in a patient with Weaver syndrome undergoing restrictive mammoplasty surgery

Science.gov (United States)

Bedirli, Nurdan; Işık, Berrin; Bashiri, Mehrnoosh; Pampal, Kutluk; Kurtipek, Ömer

2018-01-01

Abstract Rationale: Sugammadex is a cylodextrin derivate that encapsulates steroidal neuromuscular blocker agents and is reported as a safe and well-tolerated drug. In this case report, we present a patient who developed grade 3 anaphylaxis just after sugammadex administration. Patient concerns: A 22-year-old woman with diagnosis of Weaver syndrome was scheduled for bilateral mammoplasty and resection of unilateral accessory breast tissue resection. Anesthesia was induced and maintained by propofol, rocuronium, and remifentanil. At the end of the operation, sugammadex was administered and resulted in initially hypotension and bradycardia then the situation worsened by premature ventricular contraction and bigeminy with tachycardia, bronchospasm, and hypoxia. Diagnosis: The Ring and Messmer clinical severity scale grade 3 anaphylactic reaction occurred just after sugammadex injection and the patient developed prolonged hypotension with recurrent cardiac arrhythmias in postoperative 12 hours. Interventions: Treatment was initiated bolus injections of ephedrine, epinephrine, lidocaine, steroids and antihistaminic and continued with lidocaine bolus dosages and norepinephrine infusion for the postoperative period. Outcomes: The general condition of the patient improved to normal 3 hours after the sugammadex injection, and she was moved to the intensive care unit. At 2nd and 8th hours of intensive care unit follow-up, she developed premature ventricular contraction and bigeminy with the heart rate of 130 to 135 beats/min, which returned to sinus rhythm with 50 mg lidocaine. After that, no symptoms were observed and the patient was discharged to plastic surgery clinic at the following day. Lessons: Sugammadex may result in life-treating anaphylactic reaction even in a patient who did not previously expose to drug. Moreover, prolonged cardiovascular collapse and cardiac arrhythmias may occur. PMID:29505006

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

International Nuclear Information System (INIS)

Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G.

2012-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E 2 (PGE 2 , 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE 2 , which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB 1 and CB 2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB 1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB 2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac

Epidural morphine for postoperative pain relief in children

DEFF Research Database (Denmark)

Henneberg, S W; Hole, P; Haas, Inge Madsen De

1993-01-01

the investigation. We observed a change in the sleeping pattern with an increased number of sleep-induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been...

Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy

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Akihiro Kashiwai

2012-01-01

Full Text Available We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1 of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.

Anesthetic Implications of Emergent Cesarean Section in a Parturient with Marfan Syndrome Complicated by Ascending Aortic Aneurysm and Heart Failure

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Young Sung Kim

2014-07-01

Full Text Available Cardiovascular comorbidities to the Marfan syndrome may induce hemodynamic instability especially in the parturients during labor or delivery. For anesthesiologists, it is challenging to maintain hemodynamic stability during Cesarean section in those patients with Marfan syndrome. Remifentanil is an ultra-short-acting opioid with rapid onset and offset of action which provides cardiovascular stability during surgery. Together with remifentanil, the use of a laryngeal mask airway can reduce the risk of hypertensive response followed by tracheal intubation. We describe the successful administration of remifentanil and application of laryngeal mask airway for emergent Cesarean section performed under general anesthesia in a patient with Marfan syndrome complicated by ascending aortic aneurysm and heart failure. The use of remifentanil (loading dose of 1 μg/kg for 1 min, 2 min before induction; thereafter continuous infusion dose of 0.1 μg/kg/min was useful to maintain hemodynamic stability of the parturient throughout the surgery without neonatal respiratory depression. Keywords: Ascending Aortic Aneurysm; Cesarean section; Laryngeal mask airway; Marfan syndrome; Remifentanil

Cilostazol induces C-fos expression in the trigeminal nucleus caudalis and behavioural changes suggestive of headache with the migraine-like feature photophobia in female rats

DEFF Research Database (Denmark)

Christensen, S L; Petersen, Steffen; Sørensen, Dorte B

2018-01-01

-like behaviours and c-fos expression in rats. In order to evaluate the predictive validity of the model, we examined the response to the migraine specific drug sumatriptan. Methods The effect of cilostazol (125 mg/kg p.o.) in female Sprague Dawley rats was evaluated on a range of spontaneous behavioural...... parameters, light sensitivity and mechanical sensitivity thresholds. We also measured c-fos expression in the trigeminal nucleus caudalis. Results Cilostazol increased light sensitivity and grooming behaviour. These manifestations were not inhibited by sumatriptan. Cilostazol also induced c-fos expression...... in the trigeminal nucleus caudalis. Furthermore, trigeminal - but not hind paw hyperalgesia was observed. Conclusion The altered behaviours are suggestive of cilostazol induced headache with migraine-like features, but not specific. The presence of head specific hyperalgesia and the c-fos response in the trigeminal...

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

Science.gov (United States)

Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastrodin Inhibits Allodynia and Hyperalgesia in Painful Diabetic Neuropathy Rats by Decreasing Excitability of Nociceptive Primary Sensory Neurons

Science.gov (United States)

Ye, Xin; Han, Wen-Juan; Wang, Wen-Ting; Luo, Ceng; Hu, San-Jue

2012-01-01

Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients’ quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. This may result in the lacking of effective therapies for the treatment of PDN. The phenolic glucoside, gastrodin, which is a main constituent of the Chinese herbal medicine Gastrodia elata Blume, has been widely used as an anticonvulsant, sedative, and analgesic since ancient times. However, the cellular mechanisms underlying its analgesic actions are not well understood. By utilizing a combination of behavioral surveys and electrophysiological recordings, the present study investigated the role of gastrodin in an experimental rat model of STZ-induced PDN and to further explore the underlying cellular mechanisms. Intraperitoneal administration of gastrodin effectively attenuated both the mechanical allodynia and thermal hyperalgesia induced by STZ injection. Whole-cell patch clamp recordings were obtained from nociceptive, capsaicin-sensitive small diameter neurons of the intact dorsal root ganglion (DRG). Recordings from diabetic rats revealed that the abnormal hyperexcitability of neurons was greatly abolished by application of GAS. To determine which currents were involved in the antinociceptive action of gastrodin, we examined the effects of gastrodin on transient sodium currents (I NaT) and potassium currents in diabetic small DRG neurons. Diabetes caused a prominent enhancement of I NaT and a decrease of potassium currents, especially slowly inactivating potassium currents (I AS); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I NaT and total potassium current as well as I AS currents induced by STZ were normalized by GAS. This study provides a

"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

Science.gov (United States)

Pieretti, Stefano; Ranjan, Amalendu P; Di Giannuario, Amalia; Mukerjee, Anindita; Marzoli, Francesca; Di Giovannandrea, Rita; Vishwanatha, Jamboor K

2017-10-01

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans.

Science.gov (United States)

Kosek, Eva; Jensen, Karin B; Lonsdorf, Tina B; Schalling, Martin; Ingvar, Martin

2009-07-01

There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

Effect of alcoholic extract of Entada pursaetha DC on monosodium iodoacetate-induced osteoarthritis pain in rats

Directory of Open Access Journals (Sweden)

Rashmi R Kumari

2015-01-01

Interpretation & conclusions: The present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.

Attenuation of postoperative adhesions using a modeled manual therapy.

Directory of Open Access Journals (Sweden)

Geoffrey M Bove

Full Text Available Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Attenuation of postoperative adhesions using a modeled manual therapy.

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Bove, Geoffrey M; Chapelle, Susan L; Hanlon, Katherine E; Diamond, Michael P; Mokler, David J

2017-01-01

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

Multimodal approach to control postoperative pathophysiology and rehabilitation

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Kehlet, H

1997-01-01

Major surgery is still associated with undesirable sequelae such as pain, cardiopulmonary, infective and thromboembolic complications, cerebral dysfunction, nausea and gastrointestinal paralysis, fatigue and prolonged convalescence. The key pathogenic factor in postoperative morbidity, excluding...... failures of surgical and anaesthetic technique, is the surgical stress response with subsequent increased demands on organ function. These changes in organ function are thought to be mediated by trauma-induced endocrine metabolic changes and activation of several biological cascade systems (cytokines......, complement, arachidonic acid metabolites, nitric oxide, free oxygen radicals, etc). To understand postoperative morbidity it is therefore necessary to understand the pathophysiological role of the various components of the surgical stress response and to determine if modification of such responses may...

Understanding postoperative fatigue.

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Rose, E A; King, T C

1978-07-01

Performance characteristics of the central nervous, cardiovascular, respiratory and muscular systems in man postoperatively have received little investigative attention, despite the well known syndrome of postoperative fatigue. The impairmen in perception and psychomotor skills that has been shown to result from caloric restriction, bedrest, sedation and sleep deprivation suggests that a similar deficit may occur after surgical procedures. After a simple elective surgical procedure, maximal oxygen uptake decreases and the adaptability of heart rate to submaximal workloads is impaired. Similar deleterious effects on cardiorespiratory performance have been documented with starvation and bedrest; an understanding of cardiorespiratory performance postoperatively awaits further investigation. Maximal muscular force of contraction is also impaired by caloric restriction and bedrest, suggesting that similar effects may be seen in the postoperative state, although this has not been studied. A better understanding of the syndrome of postoperative fatigue could be achieved by a descriptive analysis of physiologic performance postoperatively. Such descriptive data could form the basis for objective evaluation of therapeutic measures intended to improve performance, such as nutritional supplementation and pharmacologic intervention. The observation that exercise with the patient in the supine position may decrease the impairment in maximal aerobic power otherwise expected in immobilized patients suggests that controlled exercise therapy may be of value in reducing physiologic impairment postoperatively.

Neo-adjuvant chemotherapy with cisplatin induces low expression of NMDA receptors and postoperative cognitive impairment.

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Cheng, Jing; Liu, Xiaoqing; Cao, Longhui; Zhang, Tianhua; Li, Huiting; Lin, Wenqian

2017-01-10

Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline. After the injections, the normal saline injection group was divided into 3 groups (n=5 each): a normal saline group (group S), normal saline+pentobarbital group (group SP), and normal saline+pentobarbital+operation group (group SPO).The cisplatin injection group was divided into 3 groups: a cisplatin group (group C), cisplatin+pentobarbital group (group CP), and cisplatin+pentobarbital+operation group (group CPO).Rats in the group SP, SPO,CP and CPO were anaesthetized with sodium pentobarbital and then the SPO and CPO groups underwent a simple laparotomy operation. The effects of memantine were tested through two additional groups of rats (cisplatin+memantine group (group CM) and cisplatin+pentobarbital+operation+memantine group (group CPOM)). A Morris water maze test was performed to evaluate the spatial learning and memory ability five days after anesthesia or operation. After the test, the hippocampi were removed for detection of the expression of NMDAR by western bloting. The relevant protein expression levels of PSD95 and ERK1/2 were detected by western blot analysis. Rats treated with cisplatin had a longer mean escape latency and spent a shorter amount of time in the target quadrant than did the normal saline injection rats. Furthermore, the protein expression levels of NMDA receptors, PSD95 and ERK1/2 were decreased in cisplatin group and memantine could up-regulate their expression. These results suggest

Acidic pH facilitates peripheral αβmeATP-mediated nociception in rats: differential roles of P2X, P2Y, ASIC and TRPV1 receptors in ATP-induced mechanical allodynia and thermal hyperalgesia.

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Seo, Hyoung-Sig; Roh, Dae-Hyun; Kwon, Soon-Gu; Yoon, Seo-Yeon; Kang, Suk-Yun; Moon, Ji-Young; Choi, Sheu-Ran; Beitz, Alvin J; Lee, Jang-Hern

2011-03-01

Peripheral ischemia is commonly associated with an increase in tissue ATP concentration and a decrease in tissue pH. Although in vitro data suggest that low tissue pH can affect ATP-binding affinities to P2 receptors, the mechanistic relationship between ATP and low pH on peripheral nociception has not been fully examined. This study was designed to investigate the potential role of an acidified environment on intraplantar αβmeATP-induced peripheral pain responses in rats. The mechanical allodynia (MA) produced by injection of αβmeATP was significantly increased in animals that received the drug diluted in pH 4.0 saline compared to those that received the drug diluted in pH 7.0 saline. Moreover, animals injected with αβmeATP (100 nmol) in pH 4.0 saline developed thermal hyperalgesia (TH), which did not occur in animals treated with αβmeATP diluted in pH 7.0 saline. To elucidate which receptors were involved in this pH-related facilitation of αβmeATP-induced MA and TH, rats were pretreated with PPADS (P2 antagonist), TNP-ATP (P2X antagonist), MRS2179 (P2Y1 antagonist), AMG9810 (TRPV1 antagonist) or amiloride (ASIC blocker). Both PPADS and TNP-ATP dose-dependently blocked pH-facilitated MA, while TH was significantly reduced by pre-treatment with MRS2179 or AMG9810. Moreover, amiloride injection significantly reduced low pH-induced facilitation of αβmeATP-mediated MA, but not TH. These results demonstrate that low tissue pH facilitates ATP-mediated MA via the activation of P2X receptors and ASICs, whereas TH induced by ATP under low pH conditions is mediated by the P2Y1 receptor and TRPV1, but not ASIC. Thus distinct mechanisms are responsible for the development of MA and TH under conditions of tissue acidosis and increased ATP. Copyright © 2010 Elsevier Ltd. All rights reserved.

Postoperative MRI of the ankle; Postoperative Magnetresonanztomographie des Sprunggelenks

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Sharabianlou Korth, M.; Fritz, L.B. [Rheinlandaerzte, Willich (Germany)

2017-11-15

Postoperative imaging of the ankle can be challenging, even for the experienced radiologist. Pathological and postoperative changes to the primarily complex anatomy of the ankle with its great variety of bone structures, tendons, ligaments, and soft tissue in a very limited space may cause great difficulty in differentiating underlying pathology from expected postoperative changes and artifacts, especially in magnetic resonance imaging (MRI). Selecting the appropriate radiological modality is key to making the correct diagnosis. Therefore, knowledge of the initial and current symptoms is just as important as familiarity with the most frequently performed operations in the ankle. This article aims to give its reader a summary of the most important and frequently performed operation techniques of the ankle and discusses the expected appearance and possible complications in postoperative imaging. (orig.) [German] Die postoperative radiologische Bildgebung des Sprunggelenks kann auch fuer den erfahrenen Radiologen eine besondere Herausforderung darstellen. Die komplex aufgebaute Anatomie des Sprunggelenks, mit seinen multiplen Gelenkflaechen, Sehnen, Baendern und neurovaskulaeren Strukturen auf engstem Raum, kann durch Operationen signifikant veraendert und insbesondere in der Magnetresonanztomographie (MRT) verfaelscht dargestellt werden. Fuer eine fundierte Befundung und Beurteilung der Operationsergebnisse ist die Kenntnis der praeoperativen Diagnose, Zeitpunkt und Technik der durchgefuehrten Operation(en) sowie der aktuellen klinischen Symptomatik von grosser Bedeutung. Dieser Artikel konzentriert sich auf zu erwartende radiologische Veraenderungen und gibt Tipps zur Befundung der postoperativen MRT des Sprunggelenks bei einer Auswahl relevanter operativer Eingriffe. Zudem wird auf moegliche postoperative Komplikationen und ihre radiologische Darstellung hingewiesen. (orig.)

Changes in thermal nociceptive responses in dairy cows following experimentally induced Esherichia coli mastitis

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Rasmussen, Ditte B.; Fogsgaard, Katrine; Røntved, Christine Maria

2011-01-01

Mastitis is a high incidence disease in dairy cows. The acute stage is considered painful and inflammation can lead to hyperalgesia and thereby contribute to decreased welfare. The aim of this study was to examine changes in nociceptive responses toward cutaneous nociceptive laser stimulation (NLS......) in dairy cows with experimentally induced Escherichia coli mastitis, and correlate behavioral changes in nociceptive responses to clinical and paraclinical variables....

[Postoperative unilateral acute glaucoma after abdominal surgery].

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Hidalgo Grau, L A; Opisso Juliá, L L; Roqué Meseguer, A; Yuste Graupera, M; Suñol Sala, X

2012-11-01

An early and correct diagnosis substantially improves the post-operative prognosis of acute angle closure glaucoma (AACG). A 90 year-old woman was operated on for a right colon tumour by laparotomy, under combined anaesthesia without any adverse events. Twelve hours after the operation, the patient described recurrent periorbital pain in her right eye, with ocular hyperaemia, blurred vision, and unresponsive mydriasis. A diagnosis of AACG was made, but although conservative treatment was started YAG laser iridotomies were required to reduce the intraocular pressure. In the AACG postoperative period, as well as with an eye with several predisposed local factors including genetic predisposition, female gender, hypermetropia, increased lens thickness and small corneal diameter, can be added a pupillary block induced by adrenergic and anticholinergic drugs used in anaesthetic procedures. An acute and intensive periorbital or ocular pain, with or without visual disturbance, must aware the doctor. A differential diagnosis with other postoperative ocular diseases and cranial pain causes must be done. Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Music benefits on postoperative distress and pain in pediatric day care surgery.

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Calcaterra, Valeria; Ostuni, Selene; Bonomelli, Irene; Mencherini, Simonetta; Brunero, Marco; Zambaiti, Elisa; Mannarino, Savina; Larizza, Daniela; Albertini, Riccardo; Tinelli, Carmine; Pelizzo, Gloria

2014-08-12

Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period) or the non-music group (standard postoperative care). Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC) Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (PMusic improves cardiovascular parameters, stress-induced hyperglycemia. Amelioration on pain perception is more evident in older children. Positive effects seems to be achieved by the alternation of fast, slow rhythms and pauses even in pediatric age.

Participation of peripheral TRPV1, TRPV4, TRPA1 and ASIC in a magnesium sulfate-induced local pain model in rat.

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Srebro, Dragana; Vučković, Sonja; Prostran, Milica

2016-12-17

We previously showed that magnesium sulfate (MS) has systemic antinociceptive and local peripheral pronociceptive effects. The role of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in the mechanism of action of MS has not been investigated in detail. The aim of this study was to explore the participation of TRP channels in the pronociceptive action of MS in rats after its intraplantar injection. The paw withdrawal threshold (PWT) to mechanical stimuli was measured by the electronic von Frey test. Drugs that were tested were either co-administered with an isotonic pH-unadjusted or pH-adjusted solution of MS intraplantarily, or to the contralateral paw to exclude systemic effects. We found that the subcutaneous administration of both pH-adjusted (7.4) and pH-unadjusted (about 6.0) isotonic (6.2% w/v in water) solutions of MS induce the pain at the injection site. The pH-unadjusted MS solution-induced mechanical hyperalgesia decreased in a dose-dependent manner as a consequence of co-injection of capsazepine, a selective TRPV1 antagonist (20, 100 and 500pmol/paw), RN-1734, a selective TRPV4 antagonist (1.55, 3.1 and 6.2μmol/paw), HC-030031, a selective TRPA1 antagonist (5.6, 28.1 and 140nmol/paw), and amiloride hydrochloride, a non-selective ASIC inhibitor (0.83, 2.5 and 7.55μmol/paw). In pH-adjusted MS-induced hyperalgesia, the highest doses of TRPV1, TRPV4 and TRPA1 antagonists displayed effects that were, respectively, either similar, less pronounced or delayed in comparison to the effect induced by administration of the pH-unadjusted MS solution; the ASIC antagonist did not have any effect. These results suggest that the MS-induced local peripheral mechanical hyperalgesia is mediated via modulation of the activity of peripheral TRPV1, TRPV4, TRPA1 and ASICs. Specific local inhibition of TRP channels represents a novel approach to treating local injection-related pain. Copyright © 2016 IBRO. Published by Elsevier Ltd. All

A novel model of inflammatory pain in human skin involving topical application of sodium lauryl sulfate.

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Petersen, L J; Lyngholm, A M; Arendt-Nielsen, L

2010-09-01

Sodium lauryl sulfate (SLS) is a known irritant. It releases pro-inflammatory mediators considered pivotal in inflammatory pain. The sensory effects of SLS in the skin remain largely unexplored. In this study, SLS was evaluated for its effect on skin sensory functions. Eight healthy subjects were recruited for this study. Skin sites were randomized to topical SLS 0.25, 0.5, 1, 2% and vehicle for 24 h. Topical capsaicin 1% was applied for 30 min at 24 h after SLS application. Assessments included laser Doppler imaging of local vasodilation and flare reactions, rating of spontaneous pain, assessment of primary thermal and tactile hyperalgesia, and determination of secondary dynamic and static hyperalgesia. SLS induced significant and dose-dependent local inflammation and primary hyperalgesia to tactile and thermal stimulation at 24 h after application, with SLS 2% treatment eliciting results comparable to those observed following treatment with capsaicin 1%. SLS induced no spontaneous pain, small areas of flare, and minimal secondary hyperalgesia. The primary hyperalgesia vanished within 2-3 days, whereas the skin inflammation persisted and was only partly normalized by Day 6. SLS induces profound perturbations of skin sensory functions lasting 2-3 days. SLS-induced inflammation may be a useful model for studying the mechanisms of inflammatory pain.

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

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Silva, L.C.R.; Romero, T.R.L.; Guzzo, L.S.; Duarte, I.D.G. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2012-09-21

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group). Hyperalgesia was induced by a subcutaneous intraplantar (ipl) injection of prostaglandin E{sub 2} (PGE{sub 2}, 2 µg/paw) in the rat's hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE{sub 2}, which induced hyperalgesia (mean = 83.3 ± 4.505 g). AM-251 (80 µg/paw) and AM-630 (100 µg/paw) were used as CB{sub 1} and CB{sub 2} cannabinoid receptor antagonists, respectively. Ipl injection of 40 µg dipyrone (mean = 5.825 ± 2.842 g), 20 µg diclofenac (mean = 4.825 ± 3.850 g) and 40 µg indomethacin (mean = 6.650 ± 3.611 g) elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB{sub 1} cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g), diclofenac (mean = 2.50 ± 0.8337 g) and indomethacin (mean = 6.650 ± 4.069 g) or CB{sub 2} cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g), diclofenac (mean = 6.675 ± 1.368 g) and indomethacin (mean = 2.85 ± 5.01 g). Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of

Participation of cannabinoid receptors in peripheral nociception induced by some NSAIDs

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L.C.R. Silva

2012-12-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs have been used extensively to control inflammatory pain. Several peripheral antinociceptive mechanisms have been described, such as opioid system and NO/cGMP/KATP pathway activation. There is evidence that the cannabinoid system can also contribute to the in vivo pharmacological effects of ibuprofen and indomethacin. However, there is no evidence of the involvement of the endocannabinoid system in the peripheral antinociception induced by NSAIDs. Thus, the aim of this study was to investigate the participation of the endocannabinoid system in the peripheral antinociceptive effect of NSAIDs. All experiments were performed on male Wistar rats (160-200 g; N = 4 per group. Hyperalgesia was induced by a subcutaneous intraplantar (ipl injection of prostaglandin E2 (PGE2, 2 μg/paw in the rat’s hindpaw and measured by the paw pressure test 3 h after injection. The weight in grams required to elicit a nociceptive response, paw flexion, was determined as the nociceptive threshold. The hyperalgesia was calculated as the difference between the measurements made before and after PGE2, which induced hyperalgesia (mean = 83.3 ± 4.505 g. AM-251 (80 μg/paw and AM-630 (100 μg/paw were used as CB1 and CB2 cannabinoid receptor antagonists, respectively. Ipl injection of 40 μg dipyrone (mean = 5.825 ± 2.842 g, 20 μg diclofenac (mean = 4.825 ± 3.850 g and 40 μg indomethacin (mean = 6.650 ± 3.611 g elicited a local peripheral antinociceptive effect. This effect was not antagonized by ipl CB1 cannabinoid antagonist to dipyrone (mean = 5.00 ± 0.9815 g, diclofenac (mean = 2.50 ± 0.8337 g and indomethacin (mean = 6.650 ± 4.069 g or CB2 cannabinoid antagonist to dipyrone (mean = 1.050 ± 6.436 g, diclofenac (mean = 6.675 ± 1.368 g and indomethacin (mean = 2.85 ± 5.01 g. Thus, cannabinoid receptors do not seem to be involved in the peripheral antinociceptive mechanism of the NSAIDs dipyrone, diclofenac and

The postoperative stomach

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Woodfield, Courtney A. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States); Levine, Marc S. [Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104 (United States)]. E-mail: marc.levine@uphs.upenn.edu

2005-03-01

Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients.

The postoperative stomach

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Woodfield, Courtney A.; Levine, Marc S.

2005-01-01

Gastric surgery may be performed for the treatment of a variety of benign and malignant diseases of the upper gastrointestinal tract, including peptic ulcers and gastric carcinoma. Radiographic studies with water-soluble contrast agents often are obtained to rule out leaks, obstruction, or other acute complications during the early postoperative period. Barium studies may also be obtained to evaluate for anastomotic strictures or ulcers, bile reflux gastritis, recurrent tumor, or other chronic complications during the late postoperative period. Cross-sectional imaging studies such as CT are also helpful for detecting abscesses or other postoperative collections, recurrent or metastatic tumor, or less common complications such as afferent loop syndrome or gastrojejunal intussusception. It is important for radiologists to be familiar not only with the radiographic findings associated with these various abnormalities but also with the normal appearances of the postoperative stomach on radiographic examinations, so that such appearances are not mistaken for pseudoleaks or other postoperative complications. The purpose of this article is to describe the normal postsurgical anatomy after the most commonly performed operations (including partial gastrectomy, esophagogastrectomy and gastric pull-through, and total gastrectomy and esophagojejunostomy) and to review the acute and chronic complications, normal postoperative findings, and major abnormalities detected on radiographic examinations in these patients

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2',3'-dideoxycytidine.

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Yi, Zhihua; Xie, Lihui; Zhou, Congfa; Yuan, Huilong; Ouyang, Shuai; Fang, Zhi; Zhao, Shanhong; Jia, Tianyu; Zou, Lifang; Wang, Shouyu; Xue, Yun; Wu, Bing; Gao, Yun; Li, Guilin; Liu, Shuangmei; Xu, Hong; Xu, Changshui; Zhang, Chunping; Liang, Shangdong

2018-03-01

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y 12 receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y 12 receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y 12 receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca 2+ ] i activated by the P2Y 12 receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y 12 receptor shRNA treatment inhibited 2-MeSADP-induced [Ca 2+ ] i in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y 12 receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y 12 receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

Postoperative delirium and postoperative cognitive dysfunction in the elderly - what are the differences?

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Krenk, L; Rasmussen, L S

2011-01-01

Postoperative cognitive impairment is an increasingly common problem as more elderly patients undergo major surgery. Cognitive deficits in the postoperative period cause severe problems and are associated with a marked increase in morbidity and mortality. There are two main entities of postoperat......Postoperative cognitive impairment is an increasingly common problem as more elderly patients undergo major surgery. Cognitive deficits in the postoperative period cause severe problems and are associated with a marked increase in morbidity and mortality. There are two main entities...... of postoperative cognitive decline, delirium and postoperative cognitive dysfunction, which are often reported as being part of the same continuum. Although there are similarities in the predisposing factors, it seems unlikely that they share the same pathophysiology. Both have multifactorial pathogenesis...... but differ in numerous other ways, with delirium being well-defined and acute in onset and postoperative cognitive dysfunction (POCD) being subtler and with longer duration. This review aims to provide an overview of the differences in the diagnosis of the two entities and to illustrate the methodological...

The effects of alpha2-adrenoceptor agents on anti-hyperalgesic effects of carbamazepine and oxcarbazepine in a rat model of inflammatory pain.

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Vucković, Sonja M; Tomić, Maja A; Stepanović-Petrović, Radica M; Ugresić, Nenad; Prostran, Milica S; Bosković, Bogdan

2006-11-01

In this study, the effects of yohimbine (alpha2-adrenoceptor antagonist) and clonidine (alpha2-adrenoceptor agonist) on anti-hyperalgesia induced by carbamazepine and oxcarbazepine in a rat model of inflammatory pain were investigated. Carbamazepine (10-40 mg/kg; i.p.) and oxcarbazepine (40-160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A, intraplantarly) in a paw pressure test in rats. Yohimbine (1-3 mg/kg; i.p.) significantly depressed the anti-hyperalgesic effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Both drug mixtures (carbamazepine-clonidine and oxcarbazepine-clonidine) administered in fixed-dose fractions of the ED50 (1/2, 1/4 and 1/8) caused significant and dose-dependent reduction of the hyperalgesia induced by Con A. Isobolographic analysis revealed a significant synergistic (supra-additive) anti-hyperalgesic effect of both combinations tested. These results indicate that anti-hyperalgesic effects of carbamazepine and oxcarbazepine are, at least partially, mediated by activation of adrenergic alpha2-receptors. In addition, synergistic interaction for anti-hyperalgesia between carbamazepine and clonidine, as well as oxcarbazepine and clonidine in a model of inflammatory hyperalgesia, was demonstrated.

[The effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy: a randomized controlled study].

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Karaman, Tugba; Ozsoy, Asker Zeki; Karaman, Serkan; Dogru, Serkan; Tapar, Hakan; Sahin, Aynur; Dogru, Hatice; Suren, Mustafa

A transversus abdominis plane block is a peripheral block method that has been used successfully for pain relief after total abdominal hysterectomy. However, the effects of the combination of the transversus abdominis plane block and general anesthesia on analgesic and anesthetic requirements remain unclear. This randomized placebo-controlled study is aimed to evaluate the effects of transversus abdominis plane block on analgesic and anesthetic consumption during total abdominal hysterectomy under general anesthesia. Sixty-six women undergoing total abdominal hysterectomy were randomized into two groups to receive general anesthesia alone (control group) or with transversus abdominis plane block using 20mL of 0.25% bupivacaine (transversus abdominis plane group). Intraoperative remifentanil and sevoflurane consumption were recorded. We also evaluated the postoperative pain, nausea, quality of recovery scores and rescue analgesic requirement during postoperative 24hours. The total remifentanil and sevoflurane consumption is significantly lower in transversus abdominis plane group; respectively mean (SD) 0.130 (0.25) vs. 0.094 (0.02) mcg.kg -1 .min -1 ; pplane group soon after surgery; median (range) 6 (2-10) vs. 3 (0-5); pplane group had significantly higher QoR-40 scores 190.5 (175-197) vs. 176.5 (141-187); pplane block with general anesthesia can provide reduced opioid and anesthetic consumption and can improve postoperative pain and quality of recovery scores in patients undergoing total abdominal hysterectomy. Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis.

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Hernstadt, Hayley; Wang, Shuxing; Lim, Grewo; Mao, Jianren

2009-08-25

Translocator protein 18 kDa (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is predominantly located in the mitochondrial outer membrane and plays an important role in steroidogenesis, immunomodulation, cell survival and proliferation. Previous studies have shown an increased expression of TSPO centrally in neuropathology, as well as in injured nerves. TSPO has also been implicated in modulation of nociception. In the present study, we examined the hypothesis that TSPO is involved in the initiation and maintenance of inflammatory pain using a rat model of Complete Freund's Adjuvant (CFA)-induced monoarthritis of the tibio-tarsal joint. Immunohistochemistry was performed using Iba-1 (microglia), NeuN (neurons), anti-Glial Fibrillary Acidic Protein, GFAP (astrocytes) and anti-PBR (TSPO) on Days 1, 7 and 14 after CFA-induced arthritis. Rats with CFA-induced monoarthritis showed mechanical allodynia and thermal hyperalgesia on the ipsilateral hindpaw, which correlated with the increased TSPO expression in ipsilateral laminae I-II on all experimental days. Iba-1 expression in the ipsilateral dorsal horn was also increased on Days 7 and 14. Moreover, TSPO was colocalized with Iba-1, GFAP and NeuN within the spinal cord dorsal horn. The TSPO agonist Ro5-4864, given intrathecally, dose-dependently retarded or prevented the development of mechanical allodynia and thermal hyperalgesia in rats with CFA-induced monoarthritis. These findings provide evidence that spinal TSPO is involved in the development and maintenance of inflammatory pain behaviors in rats. Thus, spinal TSPO may present a central target as a complementary therapy to reduce inflammatory pain.

Anesthetic management with scalp nerve block and propofol/remifentanil infusion during awake craniotomy in an adolescent patient -A case report-

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Sung, Bohyun; Park, Jin-Woo; Byon, Hyo-Jin; Kim, Jin-Tae; Kim, Chong Sung

2010-01-01

Despite of various neurophysiologic monitoring methods under general anesthesia, functional mapping at awake state during brain surgery is helpful for conservation of speech and motor function. But, awake craniotomy in children or adolescents is worrisome considering their emotional friabilities. We present our experience on anesthetic management for awake craniotomy in an adolescent patient. The patient was 16 years old male who would undergo awake craniotomy for removal of brain tumor. Scalp nerve block was done with local anesthetics and we infused propofol and remifentanil with target controlled infusion. The patient endured well and was cooperative before scalp suture, but when surgeon sutured scalp, he complained of pain and was suddenly agitated. We decided change to general anesthesia. Neurosurgeon did full neurologic examinations and there was no neurologic deficit except facial palsy of right side. Facial palsy had improved with time. PMID:21286435

Postoperative spine infections

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Paolo Domenico Parchi

2015-09-01

Full Text Available Postoperative spinal wound infection is a potentially devastating complication after operative spinal procedures. Despite the utilization of perioperative prophylactic antibiotics in recent years and improvements in surgical technique and postoperative care, wound infection continues to compromise patients’ outcome after spinal surgery. In the modern era of pending health care reform with increasing financial constraints, the financial burden of post-operative spinal infections also deserves consideration. The aim of our work is to give to the reader an updated review of the latest achievements in prevention, risk factors, diagnosis, microbiology and treatment of post-operative spinal wound infections. A review of the scientific literature was carried out using electronic medical databases Pubmed, Google Scholar, Web of Science and Scopus for the years 1973-2012 to obtain access to all publications involving the incidence, risk factors, prevention, diagnosis, treatment of postoperative spinal wound infections. We initially identified 119 studies; of these 60 were selected. Despite all the measures intended to reduce the incidence of surgical site infections in spine surgery, these remain a common and potentially dangerous complication.

Management of Postoperative Respiratory Failure.

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Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

2015-11-01

Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats.

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Tamaddonfard, Esmaeal; Farshid, Amir-Abbas; Eghdami, Karim; Samadi, Farzad; Erfanparast, Amir

2013-01-01

Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.

Electroacupuncture Inhibition of Hyperalgesia in Rats with Adjuvant Arthritis: Involvement of Cannabinoid Receptor 1 and Dopamine Receptor Subtypes in Striatum

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Yin Shou

2013-01-01

Full Text Available Electroacupuncture (EA has been regarded as an alternative treatment for inflammatory pain for several decades. However, the molecular mechanisms underlying the antinociceptive effect of EA have not been thoroughly clarified. Previous studies have shown that cannabinoid CB1 receptors are related to pain relief. Accumulating evidence has shown that the CB1 and dopamine systems sometimes interact and may operate synergistically in rat striatum. To our knowledge, dopamine D1/D2 receptors are involved in EA analgesia. In this study, we found that repeated EA at Zusanli (ST36 and Kunlun (BL60 acupoints resulted in marked improvements in thermal hyperalgesia. Both western blot assays and FQ-PCR analysis results showed that the levels of CB1 expression in the repeated-EA group were much higher than those in any other group (P=0.001. The CB1-selective antagonist AM251 inhibited the effects of repeated EA by attenuating the increases in CB1 expression. The two kinds of dopamine receptors imparted different actions on the EA-induced CB1 upregulation in AA rat model. These results suggested that the strong activation of the CB1 receptor after repeated EA resulted in the concomitant phenomenon of the upregulation of D1 and D2 levels of gene expression.

Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

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Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

2011-01-01

Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present...

Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats.

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Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal

2014-02-01

This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

Clinically suspected anaphylaxis induced by sugammadex in a patient with Weaver syndrome undergoing restrictive mammoplasty surgery: A case report with the literature review.

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Bedirli, Nurdan; Işık, Berrin; Bashiri, Mehrnoosh; Pampal, Kutluk; Kurtipek, Ömer

2018-01-01

Sugammadex is a cylodextrin derivate that encapsulates steroidal neuromuscular blocker agents and is reported as a safe and well-tolerated drug. In this case report, we present a patient who developed grade 3 anaphylaxis just after sugammadex administration. A 22-year-old woman with diagnosis of Weaver syndrome was scheduled for bilateral mammoplasty and resection of unilateral accessory breast tissue resection. Anesthesia was induced and maintained by propofol, rocuronium, and remifentanil. At the end of the operation, sugammadex was administered and resulted in initially hypotension and bradycardia then the situation worsened by premature ventricular contraction and bigeminy with tachycardia, bronchospasm, and hypoxia. The Ring and Messmer clinical severity scale grade 3 anaphylactic reaction occurred just after sugammadex injection and the patient developed prolonged hypotension with recurrent cardiac arrhythmias in postoperative 12 hours. Treatment was initiated bolus injections of ephedrine, epinephrine, lidocaine, steroids and antihistaminic and continued with lidocaine bolus dosages and norepinephrine infusion for the postoperative period. The general condition of the patient improved to normal 3 hours after the sugammadex injection, and she was moved to the intensive care unit. At 2nd and 8th hours of intensive care unit follow-up, she developed premature ventricular contraction and bigeminy with the heart rate of 130 to 135 beats/min, which returned to sinus rhythm with 50 mg lidocaine. After that, no symptoms were observed and the patient was discharged to plastic surgery clinic at the following day. Sugammadex may result in life-treating anaphylactic reaction even in a patient who did not previously expose to drug. Moreover, prolonged cardiovascular collapse and cardiac arrhythmias may occur. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Local analgesic effect of tramadol is not mediated by opioid receptors in early postoperative pain in rats

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Angela Maria Sousa

2015-05-01

Full Text Available Background and objectives: Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. Methods: Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5 mg, naloxone 200 μg or 0.9% NaCl, rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. Results: Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. Conclusions: Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. Resumo: Justificativa e objetivos: Tramadol é conhecido como um fármaco analgésico de ação central, usado para o tratamento de dor moderada a grave. O efeito analgésico local foi demonstrado, em parte devido ao efeito

Music benefits on postoperative distress and pain in pediatric day care surgery

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Valeria Calcaterra

2014-09-01

Full Text Available Postoperative effect of music listening has not been established in pediatric age. Response on postoperative distress and pain in pediatric day care surgery has been evaluated. Forty-two children were enrolled. Patients were randomly assigned to the music-group (music intervention during awakening period or the non-music group (standard postoperative care. Slow and fast classical music and pauses were recorded and played via ambient speakers. Heart rate, blood pressure, oxygen saturation, glucose and cortisol levels, faces pain scale and Face, Legs, Activity, Cry, Consolability (FLACC Pain Scale were considered as indicators of response to stress and pain experience. Music during awakening induced lower increase of systolic and diastolic blood pressure levels. The non-music group showed progressive increasing values of glycemia; in music-group the curve of glycemia presented a plateau pattern (P<0.001. Positive impact on reactions to pain was noted using the FLACC scale. Music improves cardiovascular parameters, stress-induced hyperglycemia. Amelioration on pain perception is more evident in older children. Positive effects seems to be achieved by the alternation of fast, slow rhythms and pauses even in pediatric age.

Investigating the relationship between persistent reflux flow on the first postoperative day and recurrent varicocele in varicocelectomy patients.

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Cil, Ahmet Said; Bozkurt, Murat; Kara Bozkurt, Duygu; Gok, Mustafa

2015-01-01

The aim of this study was to investigate the presence of persistent reflux flow on the first postoperative day using color Doppler sonography (CDS) in patients who had undergone sub-inguinal varicocelectomy, and to research the relationship between persistent reflux flow and recurrent varicocele. A total of 54 patients were included in the study. Ages of the patients were between 21 and 38 years (mean 27.3 ± 7.6). All patients were evaluated four times with CDS: preoperatively, first postoperative day, 3 months postoperative, and finally 6 months after the operation. Preoperative venous diameters were measured between 3 and 5.5 mm; mean vein diameters were 3.8 ± 0.7 mm for the left side and 3.4 ± 0.4 mm for the right side. Mean duration of reflux was 3.5 ± 0.3 seconds on the left side and 2.9 ± 0.7 seconds on the right side. First postoperative day persistent Valsalva-induced reflux flow was seen in 10 patients (18%). Mean venous diameter was measured 1.8 ± 0.9 mm. Three months after the operation, Valsalva-induced reflux flow was seen in two patients (3%) in whom reflux was not seen on the first postoperative day. After 6 months, venous diameters larger than 2 mm at rest and the occurrence of reflux during the Valsalva maneuver were considered to be a recurrence. Six months after the operation, 12 patients had recurrent varicocele. Detecting persistent reflux with CDS on the first postoperative day was found to be 85% sensitive and 100% specific for showing recurrence. Valsalva-induced persistent reflux flow investigated with CDS on the first postoperative day can be used to show success of the surgery and is also an indicator of recurrence in varicocelectomy patients.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α2-Adrenergic Receptor

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Jiho Choi

2017-10-01

Full Text Available Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal on four alternate days (days 0, 2, 4, and 6 induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36 relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36 and phospholipase A2 (0.12 mg/kg, ST36 were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α2-adrenergic receptor antagonist (idazoxan, 50 µg, but not α1-adrenergic receptor antagonist (prazosin, 30 µg, blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α2-adrenergic receptor.

Suppressive Effects of Bee Venom Acupuncture on Paclitaxel-Induced Neuropathic Pain in Rats: Mediation by Spinal α₂-Adrenergic Receptor.

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Choi, Jiho; Jeon, Changhoon; Lee, Ji Hwan; Jang, Jo Ung; Quan, Fu Shi; Lee, Kyungjin; Kim, Woojin; Kim, Sun Kwang

2017-10-31

Paclitaxel, a chemotherapy drug for solid tumors, induces peripheral painful neuropathy. Bee venom acupuncture (BVA) has been reported to have potent analgesic effects, which are known to be mediated by activation of spinal α-adrenergic receptor. Here, we investigated the effect of BVA on mechanical hyperalgesia and spinal neuronal hyperexcitation induced by paclitaxel. The role of spinal α-adrenergic receptor subtypes in the analgesic effect of BVA was also observed. Administration of paclitaxel (total 8 mg/kg, intraperitoneal) on four alternate days (days 0, 2, 4, and 6) induced significant mechanical hyperalgesic signs, measured using a von Frey filament. BVA (1 mg/kg, ST36) relieved this mechanical hyperalgesia for at least two hours, and suppressed the hyperexcitation in spinal wide dynamic range neurons evoked by press or pinch stimulation. Both melittin (0.5 mg/kg, ST36) and phospholipase A2 (0.12 mg/kg, ST36) were shown to play an important part in this analgesic effect of the BVA, as they significantly attenuated the pain. Intrathecal pretreatment with the α₂-adrenergic receptor antagonist (idazoxan, 50 µg), but not α₁-adrenergic receptor antagonist (prazosin, 30 µg), blocked the analgesic effect of BVA. These results suggest that BVA has potent suppressive effects against paclitaxel-induced neuropathic pain, which were mediated by spinal α₂-adrenergic receptor.

Does Foot Massage Relieve Acute Postoperative Pain? A Literature Review

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Chanif Chanif

2013-01-01

Full Text Available Purpose: This study aimed to examine the current state of knowledge regarding foot massageto determine if foot massage has an effect on relieving acute postoperative pain.Method: The following questions were used to guide this review: How does pain occur?What is the pain management modalities used in relieving acute postoperative pain? Does footmassage relieve acute postoperative pain? A comprehensive systematic search of publishedliterature and journal articles from Science Direct, CINAHL, PubMed, ProQuest and fromrelevant textbooks was conducted. The universal case entry website, Google-scholar was usedas well. The following keywords were used: foot massage, pain management, andpostoperative pain. Eight studies on foot massage and more than thirty related articles werereviewed.Result: Postoperative pain is caused by tissue damage that induces release of chemicalmediators from the surgical wound. The four processes of pain are transduction, transmission,perception and modulation. Pain medication is the goal standard for acute postoperative painrelief. In addition, foot massage is a modality that can be used in relieving acute postoperativepain. Massage stimulates large nerve fibers and dermatome layers which contain tactile andpressure receptors. The receptors subsequently transmit the nerve impulse to the centralnervous system. The gate control system in the dorsal horn is activated through the inhibitoryinterneuron, thus closing the gate. Subsequently, the brain does not receive the pain message.Eight reviewed studies demonstrated that foot massage relieves acute postoperative pain.However, there were some methodological limitations of these studies.Conclusion: It is recommended to examine the effect of foot massage on acute postoperativepain with high homogenous samples using various duration of massage and range of time forpain measurement at different settings.Key words: foot massage, pain management and postoperative pain.

Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.

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Wang, Dongmei; Ruan, Liqin; Hong, Yanguo; Chabot, Jean-Guy; Quirion, Rémi

2013-01-01

We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

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An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

2015-01-01

Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone

Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

2016-01-01

Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy.

Pressure pain sensitivity topographical maps reveal bilateral hyperalgesia of the hands in patients with unilateral carpal tunnel syndrome.

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Fernández-de-Las-Peñas, César; Madeleine, Pascal; Martínez-Perez, Almudena; Arendt-Nielsen, Lars; Jiménez-García, Rodrigo; Pareja, Juan A

2010-08-01

To assess topographical pressure pain sensitivity maps of the hand in patients with unilateral carpal tunnel syndrome (CTS) as compared with healthy subjects. A total of 20 women with CTS (ages 32-52 years) and 20 healthy matched women (ages 32-51 years) were recruited. Pressure pain thresholds (PPTs) were measured bilaterally over 30 locations of the palm of each hand by an assessor blinded to the subjects' conditions. Patients showed lower PPTs in both hands in all of the measurement points as compared with controls (P < 0.001 for all). PPTs were lower in those points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers (P < 0.001). CTS patients showed lower PPT levels in dermatomes C6, C7, and C8 when compared with healthy controls (P < 0.001 for all), but without differences between dermatomes (P = 0.4). PPT was negatively correlated with both hand pain intensity and duration of symptoms (P < 0.001 for all). Our findings revealed bilateral generalized pressure pain hyperalgesia in unilateral CTS because lower PPT levels were found in all of the points. The pressure pain hyperalgesia was not uniformly distributed since PPTs were lower in points over the proximal phalanx of the fingers and the thenar eminency as compared with those points located over the distal phalanx of the fingers. The decrease in PPT levels was associated with the intensity and the duration of the pain symptoms, supporting a role of both peripheral and central sensitization mechanisms in this pain condition.

Inflammatory sensitization of nociceptors depends on activation of NMDA receptors in DRG satellite cells.

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Ferrari, Luiz Fernando; Lotufo, Celina Monteiro; Araldi, Dionéia; Rodrigues, Marcos A; Macedo, Larissa P; Ferreira, Sérgio H; Parada, Carlos Amilcar

2014-12-23

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats

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Ohtani N

2016-10-01

Full Text Available Norimasa Ohtani, Eiji Masaki Division of Dento-oral Anesthesiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan Background: Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats.Methods: Male Sprague-Dawley rats (250–300 g were anesthetized with sevoflurane and an intrathecal (IT catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole, or a D2-like receptor antagonist (sulpiride was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision.Results: Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect.Conclusion: A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold. Keywords: postoperative pain, descending pathway

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats.

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Merlos, Manuel; Portillo-Salido, Enrique; Brenchat, Alex; Aubel, Bertrand; Buxens, Jordi; Fisas, Angels; Codony, Xavier; Romero, Luz; Zamanillo, Daniel; Vela, José Miguel

2018-06-19

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated 'raw' form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 =2.0±0.5mg/kg, i.p.; theoretical ED 50 =3.8±0.4mg/kg, i.p.) and thermal (experimental ED 50 =2.3±0.5mg/kg, i.p.; theoretical ED 50 =9.8±0.8mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. Copyright © 2018. Published by Elsevier B.V.

Preventative and therapeutic effects of a GABA transporter 1 inhibitor administered systemically in a mouse model of paclitaxel-induced neuropathic pain

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Willias Masocha

2016-12-01

Full Text Available Background There is a dearth of drugs to manage a dose-limiting painful peripheral neuropathy induced by paclitaxel in some patients during the treatment of cancer. Gamma-aminobutyric acid transporter-1 (GAT-1 whose expression is increased in the brain and spinal cord during paclitaxel-induced neuropathic pain (PINP might be a potential therapeutic target for managing PINP. Thus, our aim was to evaluate if systemic administration of a GAT-1 inhibitor ameliorates PINP. Methods The reaction latency to thermal stimuli (hot plate test; at 55 °C and cold stimuli (cold plate test; at 4 °C of female BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel, its vehicle, and/or a selective GAT-1 inhibitor NO-711. The effects of NO-711 on motor coordination were evaluated using the rotarod test at a constant speed of 4 rpm or accelerating mode from 4 rpm to 40 rpm over 5 min. Results The coadministration of paclitaxel with NO-711 3 mg/kg prevented the development of paclitaxel-induced thermal hyperalgesia and cold allodynia at day 7 after drug treatment. NO-711 at 3 mg/kg produced antihyperalgesic activity up to 1 h and antiallodynic activity up to 2 h in mice with established paclitaxel-induced thermal hyperalgesia and cold allodynia. No motor deficits were observed with NO-711 at a dose of 3 mg/kg, whereas a higher dose 5 mg/kg caused motor impairment and reduced mean time spent on the rotarod at a constant speed of 4 rpm. However, at a rotarod accelerating mode from 4 rpm to 40 rpm over 5 min, NO-711 3 mg/kg caused motor impairment up to 1 h, but had recovered by 2 h. Conclusions These results show that systemic administration of the GAT-1 inhibitor NO-711 has preventative and therapeutic activity against paclitaxel-induced thermal hyperalgesia and cold allodynia. NO-711’s antiallodynic effects, but not antihyperalgesic effects, were independent of its motor impairment/sedation properties. Thus, low doses of GAT-1

Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

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Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

2018-05-17

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All

Preoperative alcoholism and postoperative morbidity

DEFF Research Database (Denmark)

Tonnesen, H; Kehlet, H

1999-01-01

BACKGROUND: Preoperative risk assessment has become part of daily clinical practice, but preoperative alcohol abuse has not received much attention. METHODS: A Medline search was carried out to identify original papers published from 1967 to 1998. Relevant articles on postoperative morbidity...... in alcohol abusers were used to evaluate the evidence. RESULTS: Prospective and retrospective studies demonstrate a twofold to threefold increase in postoperative morbidity in alcohol abusers, the most frequent complications being infections, bleeding and cardiopulmonary insufficiency. Wound complications...... to postoperative morbidity. CONCLUSION: Alcohol consumption should be included in the preoperative assessment of likely postoperative outcome. Reduction of postoperative morbidity in alcohol abusers may include preoperative alcohol abstinence to improve organ function, or perioperative alcohol administration...

Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

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Guzzetti Stefano

2009-04-01

Full Text Available Abstract Background Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA with volatile-based neuroanaesthesia (VA has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. Methods/Design NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III and Glasgow Coma Scale (GCS equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil. The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point. Two statistical comparisons have been planned: 1 sevoflurane + fentanyl vs. propofol + remifentanil; 2 sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a measurement of urinary catecholamines and plasma and urinary cortisol and (b estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded

Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial--the NeuroMorfeo trial.

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Citerio, Giuseppe; Franzosi, Maria Grazia; Latini, Roberto; Masson, Serge; Barlera, Simona; Guzzetti, Stefano; Pesenti, Antonio

2009-04-06

Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaesthesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score > or = 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative

[Postoperative cognitive deficits].

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Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Slick (Kcnt2 Sodium-Activated Potassium Channels Limit Peptidergic Nociceptor Excitability and Hyperalgesia

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Danielle L Tomasello

2017-09-01

Full Text Available The Slick (Kcnt2 sodium-activated potassium (K Na channel is a rapidly gating and weakly voltage-dependent and sodium-dependent potassium channel with no clearly defined physiological function. Within the dorsal root ganglia (DRGs, we show Slick channels are exclusively expressed in small-sized and medium-sized calcitonin gene–related peptide (CGRP-containing DRG neurons, and a pool of channels are localized to large dense-core vesicles (LDCV-containing CGRP. We stimulated DRG neurons for CGRP release and found Slick channels contained within CGRP-positive LDCV translocated to the neuronal membrane. Behavioral studies in Slick knockout (KO mice indicated increased basal heat detection and exacerbated thermal hyperalgesia compared with wild-type littermate controls during neuropathic and chronic inflammatory pain. Electrophysiologic recordings of DRG neurons from Slick KO mice revealed that Slick channels contribute to outward current, propensity to fire action potentials (APs, and to AP properties. Our data suggest that Slick channels restrain the excitability of CGRP-containing neurons, diminishing pain behavior after inflammation and injury.

Transversus abdominis plane block as a component of multimodal analgesia for laparoscopic cholecystectomy.

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Oksar, Menekse; Koyuncu, Onur; Turhanoglu, Selim; Temiz, Muhyittin; Oran, Mustafa Cemil

2016-11-01

To evaluate and compare intercostal-iliac transversus abdominis plane (TAP) and oblique subcostal TAP (OSTAP) blocks for multimodal analgesia in patients receiving laparoscopic cholecystectomy. A prospective, randomized, double-blinded clinical study. Operating room, postoperative recovery area, and ward. In total, 60 laparoscopic cholecystectomy patients (43 women, 17 men, American Society of Anesthesiologists grades I-II) were enrolled from the general surgery department of our tertiary care center. The patients were assigned to 1 of the 3 groups. Group 1 received TAP blocks (n=20), group 2 received OSTAP blocks (n=20), and group 3 patients were used as controls and received patient-controlled analgesia (PCA) only (n=20). After the induction of anesthesia, blocks were performed bilaterally in study groups 1 and 2, using 20mL of lidocaine (5mg/mL). PCA with intravenous tramadol was routinely provided for all patients during the first 24hours. The intraoperative use of remifentanil, postoperative visual analog scale (VAS) scores, demand for PCA, and total analgesic consumption were recorded. The patients in the control group had greater analgesic demands and analgesic consumption than did those in groups 1 and 2. However, patients in the OSTAP group had lower VAS scores than did those in groups 1 and 3. The demand for analgesia was greater in the control group than in groups 1 and 2. Moreover, lower VAS scores were recorded in the OSTAP group than in groups 1 and 3 and were positively correlated with total PCA consumption among all patients. However, postoperative VAS scores were negatively correlated with the total intraoperative consumption of remifentanil at 24hours. TAP and OSTAP blocks improved postoperative analgesia in patients receiving laparoscopic cholecystectomy, which resulted in lower VAS scores and reduction in total analgesic consumption. Copyright © 2016 Elsevier Inc. All rights reserved.

Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

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Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

2017-03-01

Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

Flurbiprofen Axetil Provides Effective Analgesia Without Changing the Pregnancy Rate in Ultrasound-Guided Transvaginal Oocyte Retrieval: A Double-Blind Randomized Controlled Trial.

Science.gov (United States)

Zhao, Hong; Feng, Yi; Jiang, Yan; Lu, Qun

2017-10-01

In this prospective double-blind randomized study, we evaluated the analgesic effect and potential effect on pregnancy rate of the nonsteroidal anti-inflammatory drug flurbiprofen axetil in patients undergoing ultrasound-guided transvaginal oocyte retrieval under propofol-remifentanil anesthesia. A total of 200 patients scheduled to undergo ultrasound-guided transvaginal oocyte retrieval were randomly allocated to receive 1.5 mg/kg of flurbiprofen axetil (FA group) or placebo (control group) 30 minutes before the procedure. Postoperative pain scores, embryo implantation rate, and pregnancy rate were recorded. Neuroendocrine biomarkers and prostaglandin E2 levels in follicular fluid were tested after oocyte retrieval. Patients in the FA group awakened earlier after surgery than patients in the control group (3.3 ± 2.6 vs 5.3 ± 3.4 minutes, P Flurbiprofen axetil given before ultrasound-guided transvaginal oocyte retrieval for patients under propofol-remifentanil general anesthesia relieves pain without any detrimental effect on clinical pregnancy rate.

Postoperative radiology

International Nuclear Information System (INIS)

Burhenne, H.J.

1989-01-01

This paper reports on the importance of postoperative radiology. Most surgical procedures on the alimentary tract are successful, but postoperative complications remain a common occurrence. The radiologist must be familiar with a large variety of possible surgical complications, because it is this specialty that is most commonly called on to render a definitive diagnosis. The decision for reoperation, for instance, is usually based on results from radiologic imaging techniques. These now include ultrasonography, CT scanning, needle biopsy, and interventional techniques in addition to contrast studies and nuclear medicine investigation

POSTOPERATIVE NAUSEA AND VOMITING | Yusufu | Annals of ...

African Journals Online (AJOL)

Antiemetics, acupuncture and other drugs are used to prevent and treat postoperative nausea and vomiting. Those that manage patients in the postoperative period should endeavour to make postoperative nausea and vomiting as unacceptable as postoperative pain. Key words: Postoperative, Nausea, Vomiting, Narcotics, ...

Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.

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Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

2015-11-01

Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. Copyright © 2015 Elsevier Inc. All rights reserved.

Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

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Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

1981-12-01

PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

The ultrasound-guided nerve blocks of abdominal wall contributed to anesthetic management of cholecystectomy in a patient with Becker muscular dystrophy without using muscle relaxants.

Science.gov (United States)

Iwata, Masato; Kuzumoto, Naoya; Akasaki, Yuka; Morioka, Masayo; Nakayama, Kana; Matsuzawa, Nobuyoshi; Kimoto, Katsuhiro; Shimomura, Toshiyuki

2017-01-01

Becker muscular dystrophy (BMD) is a progressive neuromuscular disorder caused by mutations in the dystrophin gene. The sensitivity to non-depolarizing muscle relaxant in a patient with muscle dystrophy is reportedly higher than that in normal individuals, and the duration of the effect is known to be prolonged. In this report, we present the case of a 58-year-old man with BMD who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis under total intravenous anesthesia without the use of muscle-relaxant drugs and supplemented with regional anesthesia. Anesthesia was induced and maintained with propofol, remifentanil, and fentanyl; ultrasound-guided bilateral rectus sheath block (RSB) and right-sided subcostal transversus abdominis plane block (TAP) were performed. The procedure required conversion to open surgery because of hard conglutination; intraoperative and postoperative periods were uneventful. Adequate analgesia was maintained after extubation because of the effect of RSB and TAP.

Effects of Hydrogen-Rich Saline on Hepatectomy-Induced Postoperative Cognitive Dysfunction in Old Mice.

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Tian, Yue; Guo, Shanbin; Zhang, Yan; Xu, Ying; Zhao, Ping; Zhao, Xiaochun

2017-05-01

This study aims to investigate the protective effects and underlying mechanisms of hydrogen-rich saline on the cognitive functions of elder mice with partial hepatectomy-induced postoperative cognitive dysfunction (POCD). Ninety-six old male Kunming mice were randomly divided into 4 groups (n = 24 each): control group (group C), hydrogen-rich saline group (group H), POCD group (group P), and POCD + hydrogen-rich saline group (group PH). Cognitive function was subsequently assessed using Morris water-maze (MWM) test. TNF-α and IL-1β levels were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, along with NF-κB activity determined by ELISA. The morphology of hippocampal tissues were further observed by HE staining. Learning and memory abilities of mice were significantly impaired at day 10 and day 14 post-surgery, as partial hepatectomy significantly prolonged the escape latency, decreased time at the original platform quadrant and frequency of crossing in group P when compared to group C (p hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.

D2-like receptors in the descending dopaminergic pathway are not involved in the decreased postoperative nociceptive threshold induced by plantar incision in adult rats.

Science.gov (United States)

Ohtani, Norimasa; Masaki, Eiji

2016-01-01

Approximately half of all patients who undergo surgery develop postoperative pain, the mechanisms of which are not well understood by anesthesiologists. D2-like receptors in the descending dopaminergic pathway play an important role in regulation of pain transmission in the spinal cord. Impairment of inhibitory neurons in the spinal cord is suggested as part of the mechanism for neuropathic pain, which is one component of postoperative pain. The purpose of this study was to investigate whether impairment of D2-like receptors in the descending dopaminergic pathway in the spinal cord is involved in the decreased postoperative nociceptive threshold in rats. Male Sprague-Dawley rats (250-300 g) were anesthetized with sevoflurane and an intrathecal (IT) catheter was implanted. Six days later, a plantar incision was made. On the following day, saline, a D2-like receptor agonist (quinpirole), or a D2-like receptor antagonist (sulpiride) was administered intrathecally. Thermal and mechanical nociceptive responses were assessed by exposure to infrared radiant heat and the von Frey filament test before and after plantar incision. Plantar incision decreased both thermal latency and the mechanical nociceptive threshold. IT administration of quinpirole inhibited the nociceptive responses induced by plantar incision, but sulpiride had no effect. A D2-like receptor agonist had antinociceptive effects on the hypersensitivity response triggered by a surgical incision, but a D2-like receptor antagonist had no effect on this response. These results suggest that impairment and/or modification of D2-like receptors in the descending dopaminergic pathway in the spinal cord is not involved in the postoperative decrease in nociceptive threshold.

[Influence of the occlusal interference time on masticatory muscle mechanical hyperalgesia in rats].

Science.gov (United States)

Liu, Cun-rui; Xu, Xiao-xiang; Cao, Ye; Xie, Qiu-fei

2016-02-18

To investigate the relationship between the removal time of 0.2 mm occlusal interference and the recovery of masticatory muscle mechanical hyperalgesia in rats. Forty male Sprague-Dawley rats (200-220 g) were randomly assigned to eight groups, with five rats in each group: (1) naive group: these rats were anesthetized and their mouths were forced open for about 5 min (the same duration as the other groups), but restorations were not applied; (2) sham-occlusal interference control group: bands were bonded to the right maxillary first molars which did not interfere with occlusion; (3)occlusal interference group: 0.2 mm thick crowns were bonded to the right maxillary first molars; (4) 2, 3, 4, 5, and 6 d removal of occlusal interference groups: 0.2 mm thick crowns were bonded to the right maxillary first molars and removed on days 2, 3, 4, 5, and 6. The naive group and sham-occlusal interference control group were control groups. The other groups were experimental groups. Bilateral masticatory muscle mechanical withdrawal thresholds were tested on pre-application days 1, 2, and 3, and on post-application days 1, 3, 5, 7, 10, 14, 21 and 28. The rats were weighed on pre-application day 1 and on post-application days 1, 2, 3, 4, 5, 6, and 7. Between the naive group and the sham-occlusal interference control group, there was no significant difference in the masticatory muscle mechanical withdrawal threshold of bilateral temporalis and masseters at each time point. No significant difference was detected between the contralateral side and ipsilateral side in experimental groups (P>0.05). In the 2, 3, 4, and 5 d removal of occlusal interference groups, the masticatory muscle mechanical withdrawal thresholds decreased after occlusal interference and increased after removal of the crowns and recovered to the baseline on days 7, 10, 14, and 14, respectively [the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (137.46 ± 2.08) g, (139.02 ± 2

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

Science.gov (United States)

Xiao, Xing; Zhao, Xiao-Tao; Xu, Ling-Chi; Yue, Lu-Peng; Liu, Feng-Yu; Cai, Jie; Liao, Fei-Fei; Kong, Jin-Ge; Xing, Guo-Gang; Yi, Ming; Wan, You

2015-04-01

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

Postoperative mental confusion--association with postoperative hypoxemia

DEFF Research Database (Denmark)

Rosenberg, J; Kehlet, H

1993-01-01

under general anesthesia, were monitored for oxygen saturation (SpO2) with a pulse oximeter on a preoperative night and on the second night after operation (11:00 PM to 7:00 AM). All patients were tested with a mental test questionnaire (the Hodkinson modification of the original Roth-Hopkins test...... major surgery had decreased mental function on the third day (p operation, whereas minor surgery did not impair mental function. There was a significant correlation between mental function on the third day after operation and mean SpO2 on the second postoperative.......04). During stepwise multiple regression analysis in patients undergoing major surgery, a significant relationship was found between postoperative mental test score and SpO2 (p mental function and other perioperative variables (age, premedication dose, duration of operation...

[Postoperative Chylotholax;Intraoperative Prevention and Postoperative Management].

Science.gov (United States)

Saito, Tomohito; Kariya, Shuji; Murakawa, Tomohiro

2017-07-01

Postoperative chylothorax is a relatively rare but potentially fatal complication caused by iatrogenic injury to thoracic duct system, with an incidence ranging from 2 to 4% after major lung surgery or esophagectomy. The pathophysiologic features of chylothorax include dehydration, loss of nutrients and immunological components. Intraopreative prevention is the first step for the management, and treatment options include conservative therapy, percutaneous intervention, and redo-operation. Although the treatment algorithm has not been standardized, chylothorax which is refractory to conservative treatment, or that with high output greater than 1,000 ml/day should be treated aggressively with thoracic duct embolization or redo-operation in a timely fashion. We herein review the anatomy and physiology of thoracic duct system and describe the overview of prevention and each theapeutic options of postoperative chylothorax.

EARLY POSTOPERATIVE COMPLICATIONS AFTER RADICAL CYSTECTOMY

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V. O. Mager

2014-08-01

Full Text Available Radical cystectomy (RCE is associated with a considerable number of early postoperative complications as before. Based on 10 years’ experience, this paper demonstrates the frequency (33.9 % and types of early complications following RCE, as well as postoperative mortality (5.5 % and its resulting causes. Although postoperative mortality is relatively low today, the frequency of early postoperative complications remains high as before.

Influence of different phacoemulsification incision on postoperative corneal astigmatism for cataract patients

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Zhao-Rong Zeng

2014-05-01

Full Text Available AIM: To compare the effect of different phacoemulsification incision on postoperative corneal astigmatism for cataract patients. METHODS: The cataract patients were selected in our hospital. The patients were divided into control group(corneal limbus opposite curved scleral tunnel incision groupand observation group(above the top of cornea or temporal transparent corneal incision grouprandomly. At 1wk; 1 and 3mo after surgery, the change of corneal astigmatism and vision of the patients in two groups were compared and analyzed. RESULTS:Compared with control group, 1wk; 1 and 3mo after surgery, the average corneal astigmatism and surgically induced corneal astigmatism of the patients in observation group were decreased significantly. The visual acuity and corrected visual acuity were increased significantly. There was statistically significant(PPCONCLUSION: Center distance and small incision corneal phacoemulsification can reduce postoperative astigmatism and improve postoperative visual acuity for cataract patients. It provides guarantee for further strengthen the clinical treated effect for cataract patients.

Female Adults with Patellofemoral Pain Are Characterized by Widespread Hyperalgesia, Which Is Not Affected Immediately by Patellofemoral Joint Loading.

Science.gov (United States)

Pazzinatto, Marcella Ferraz; de Oliveira Silva, Danilo; Barton, Christian; Rathleff, Michael Skovdal; Briani, Ronaldo Valdir; de Azevedo, Fábio Mícolis

2016-10-01

Compare pressure pain thresholds (PPTs) at the knee and a site remote to the knee in female adults with patellofemoral pain (PFP) to pain-free controls before and after a patellofemoral joint (PFJ) loading protocol designed to aggravate symptoms. Cross-sectional study SETTING: Participants were recruited via advertisements in fitness centers, public places for physical activity and universities. Thirty-eight females with patellofemoral pain, and 33 female pain-free controls. All participant performed a novel PFJ loading protocol involving stair negotiation with an extra load equivalent 35% of body mass. PPTs and current knee pain (measured on a visual analogue scale) was assessed before and after the loading protocol. PPTs were measured at four sites around the knee and one remote site on the upper contralateral limb. Females with PFP demonstrated significantly lower PPTs locally and remote to the knee, both before and after the PFJ loading protocol when compared to control group. Following the loading protocol, PPTs at knee were significantly reduced by 0.54 kgf (95%CI = 0.33; 0.74) for quadriceps tendon, 0.38 kgf (95%CI = 0.14; 0.63) for medial patella, and 0.44 kgf (95%CI = 0.18; 0.69) for lateral patella. No significant change in PPT remote to the knee was observed - 0.10 kgf (95%CI = -0.04; 0.24). Female adults with PFP have local and widespread hyperalgesia compared to pain free controls. A novel loading protocol designed to aggravate symptoms, lowers the PPTs locally at the knee but has no effect on PPT on the upper contralateral limb. This suggests widespread hyperalgesia is not affected by acute symptom aggravation. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Characteristics of postoperative peritonitis].

Science.gov (United States)

Lock, J F; Eckmann, C; Germer, C-T

2016-01-01

Postoperative peritonitis is still a life-threatening complication after abdominal surgery and approximately 10,000 patients annually develop postoperative peritonitis in Germany. Early recognition and diagnosis before the onset of sepsis has remained a clinical challenge as no single specific screening test is available. The aim of therapy is a rapid and effective control of the source of infection and antimicrobial therapy. After diagnosis of diffuse postoperative peritonitis surgical revision is usually inevitable after intestinal interventions. Peritonitis after liver, biliary or pancreatic surgery is managed as a rule by means of differentiated therapy approaches depending on the severity.

Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain

DEFF Research Database (Denmark)

Carstensen, M; Møller, A M

2010-01-01

In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient-contr...... heterogeneity of studies and small sample sizes, larger double-blinded randomized studies showing greater degree of homogeneity are required to confirm these findings...

Healthy volunteers can be phenotyped using cutaneous sensitization pain models.

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Mads U Werner

Full Text Available BACKGROUND: Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. METHODS: We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]. Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C, the brief thermal sensitization (BTS, and the burn injury (BI models. Three studies included both the H/C and BTS models. RESULTS: Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into 'small area' (1(st quartile [75%] responders: 56-76% of subjects consistently fell into same 'small-area' or 'large-area' category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm and BTS (thigh models. CONCLUSION: Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.

Vendor-derived differences in injury-induced pain phenotype and pharmacology of Sprague-Dawley rats

DEFF Research Database (Denmark)

Kristensen, P J; Heegaard, A M; Kristensen, Sara Hestehave

2017-01-01

's adjuvant (CFA) hindpaw inflammation was induced in male SD rats sourced from three to four different vendors, respectively. Neuropathic hypersensitivity was evaluated over 58 days using von Frey filaments, pinprick stimulation and the hot plate test. Pharmacological sensitivity was evaluated by treatment...... with gabapentin (100 mg/kg, p.o.) or morphine (3 mg/kg, s.c.). CFA-induced hyperalgesia and sensitivity to morphine (0.3-6 mg/kg, s.c.) was measured using a digital Randall-Selitto device. In addition, paw weight gain was used as an index of peripheral oedema. RESULTS: Significant differences between the vendor...... to gabapentin varied enormously, the response to morphine was both robust and much more consistent between sub-strains. Despite a similar degree of CFA-induced hypersensitivity, the paw oedema level differed between sub-strains. Here, morphine dose-dependently alleviated the CFA-induced hypersensitivity...

Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

Science.gov (United States)

Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

2016-01-11

The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

Postoperative diagnosis of the temporomandibular joint; Postoperative Kiefergelenkdiagnostik

Energy Technology Data Exchange (ETDEWEB)

Robinson, S. [Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria). Abt. fuer Osteologie; Undt, G. [Universitaetsklinik fuer Mund-, Kiefer- und Gesichtschirurgie, Vienna (Austria)

2001-09-01

Postoperative management of patients suffering from symptoms of the temporomandibular joint does not differ considerably from the one of preoperative examination protocols. Knowledge of previous surgery helps to plan patient work-up and to interpret normal postoperative findings (eminectomy, discectomy, susceptibility artefacts from metallic residues..) and typical complications (intraarticular loose bodies, dislocations, avascular necrosis, foreign body granulomatous reactions) appropriately. (orig.) [German] Wie auch in anderen Koerperregionen differiert das Diagnoseprotokoll von prae- und postoperativen Patienten mit Beschwerden des Kiefergelenks nicht wesentlich voneinander. Die Kenntnis des vorangegangenen Eingriffs hilft allerdings, die Untersuchung entsprechend zu planen und den Befund im Kontext richtig zu bewerten, um moegliche Komplikationen (intraartikulaere Fragmente, Dislokationen, avaskulaere Nekrose, Fremdkoerperreaktionen) und zu erwartende Befunde (Eminektomie, Diskektomie, Metallartefakte usw.) richtig zu interpretieren. (orig.)

TRPV1 antagonist attenuates postoperative hypersensitivity by central and peripheral mechanisms

Czech Academy of Sciences Publication Activity Database

Uchytilová, Eva; Špicarová, Diana; Paleček, Jiří

2014-01-01

Roč. 10, č. 2014 (2014), s. 67 ISSN 1744-8069 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) LH12058; GA ČR(CZ) GPP303/12/P510 Institutional support: RVO:67985823 Keywords : SB366791 * TRPV1 * allodynia * hyperalgesia * surgical pain * spinal cord Subject RIV: FH - Neurology Impact factor: 3.654, year: 2014

Effects of posture on postoperative pulmonary function

DEFF Research Database (Denmark)

Nielsen, K G; Holte, Kathrine; Kehlet, H

2003-01-01

effect on postoperative pulmonary function in the sitting or standing position compared with the supine. Thus, avoidance of the supine position may improve postoperative pulmonary function. Three of six studies showed a positive effect on postoperative pulmonary function of the lateral side compared......BACKGROUND: Pulmonary morbidity is still a relevant complication to major surgery despite improvements in surgical technique and anaesthetic methods. Postoperative posture may be a pathogenic factor, but the effects of changes in postoperative posture on pulmonary function have not been reviewed...... with the supine. Thus, the lateral position has limited effects on pulmonary function. CONCLUSION: Changes of postoperative position from supine to sitting or standing are of major importance in the interpretation of postoperative pulmonary outcome studies and in future strategies to improve pulmonary outcome....

Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531 influences the analgesic response to the short acting opioid Remifentanil in humans

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Schalling Martin

2009-07-01

Full Text Available Abstract Background There is evidence from animal studies that serotonin (5-HT can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531. The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on μ-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS. All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. Results At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG as compared to those with high expression(LA/LA, p Conclusion This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of

A prospective clinical study to compare the depth of anaesthesia, the wake-up time and the wake-up behaviour for total intravenous anaesthesia (TIVA) with Remifentanil and Propofol between two anaesthetic methods (TCI versus OTCI) in elective vasovasostomy patients

OpenAIRE

Baschin, Alexander

2010-01-01

Background. The performance of safe anaesthesia with fewer complications combined with fast wake-up and prompt return of cognitive functions on completion of surgery appear to be possible with the introduction of rapid-acting and more controllable drugs, such as Propofol and Remifentanil, as well as the use of computerised application systems. Target-controlled perfusor systems based on the Marsh model are common in daily practice. The target values in the target-controlled infusion systems (...

脊髄におけるプロスタグランジン

OpenAIRE

山本 登志子,

2005-01-01

In the spinal cord, prostaglandins participate in the pain transmission including hyperalgesia and allodynia. Prostaglandin D２ and E２ induce hyperalgesia, while prostaglandin E２ and F２α induce allodynia. PGF２α synthase （PGFS） produce two stereoisomers of PGF２, PGF２α and９α, １１β-PGF２ which are synthesized from PGH２ and PGD２, respectively, by the distinct reductions in the prostaglandin synthesis pathway. Because the two reduction are occurred in the different active sites, PGFS is a multifuncti...

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

Science.gov (United States)

Sayeli, Vijaykumar; Nadipelly, Jagan; Kadhirvelu, Parimala; Cheriyan, Binoy Varghese; Shanmugasundaram, Jaikumar; Subramanian, Viswanathan

2018-04-13

Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3',4'-dimethoxy flavonol, 6,3'-dimethoxy flavonol, 7,2'-dimethoxy flavonol and 7,3'-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice. A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitable in vitro assays. A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner. These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

Perioperative management of a morbidly obese pregnant patient undergoing cesarean section under general anesthesia - case report

Directory of Open Access Journals (Sweden)

Márcio Luiz Benevides

Full Text Available Abstract Background and objectives: The increased prevalence of obesity in the general population extends to women of reproductive age. The aim of this study is to report the perioperative management of a morbidly obese pregnant woman, body mass index >50 kg/m2, who underwent cesarean section under general anesthesia. Case report: Pregnant woman in labor, 35 years of age, body mass index 59.8 kg/m2. Cesarean section was indicated due to the presumed fetal macrosomia. The patient refused spinal anesthesia. She was placed in the ramp position with cushions from back to head to facilitate tracheal intubation. Another cushion was placed on top of the right gluteus to create an angle of approximately 15° to the operating table. Immediately before induction of anesthesia, asepsis was carried out and sterile surgical fields were placed. Anesthesia was induced in rapid sequence, with Sellick maneuver and administration of remifentanil, propofol, and succinilcolina. Intubation was performed using a gum elastic bougie, and anesthesia was maintained with sevoflurane and remifentanil. The interval between skin incision and fetal extraction was 21 min, with the use of a Simpson's forceps scoop to assist in the extraction. The patient gave birth to a newborn weighing 4850 g, with Apgar scores of 2 in the 1st minute (received positive pressure ventilation by mask for about 2 min and 8 in the 5th minute. The patient was extubated uneventfully. Multimodal analgesia and prophylaxis of nausea and vomiting was performed. Mother and newborn were discharged on the 4th postoperative day.

Battery of behavioral tests in mice to study postoperative delirium

Science.gov (United States)

Peng, Mian; Zhang, Ce; Dong, Yuanlin; Zhang, Yiying; Nakazawa, Harumasa; Kaneki, Masao; Zheng, Hui; Shen, Yuan; Marcantonio, Edward R.; Xie, Zhongcong

2016-01-01

Postoperative delirium is associated with increased morbidity, mortality and cost. However, its neuropathogenesis remains largely unknown, partially owing to lack of animal model(s). We therefore set out to employ a battery of behavior tests, including natural and learned behavior, in mice to determine the effects of laparotomy under isoflurane anesthesia (Anesthesia/Surgery) on these behaviors. The mice were tested at 24 hours before and at 6, 9 and 24 hours after the Anesthesia/Surgery. Composite Z scores were calculated. Cyclosporine A, an inhibitor of mitochondria permeability transient pore, was used to determine potential mitochondria-associated mechanisms of these behavioral changes. Anesthesia/Surgery selectively impaired behaviors, including latency to eat food in buried food test, freezing time and time spent in the center in open field test, and entries and duration in the novel arm of Y maze test, with acute onset and various timecourse. The composite Z scores quantitatively demonstrated the Anesthesia/Surgery-induced behavior impairment in mice. Cyclosporine A selectively ameliorated the Anesthesia/Surgery-induced reduction in ATP levels, the increases in latency to eat food, and the decreases in entries in the novel arm. These findings suggest that we could use a battery of behavior tests to establish a mouse model to study postoperative delirium. PMID:27435513

Psychosocial factors partially mediate the relationship between mechanical hyperalgesia and self-reported pain.

Science.gov (United States)

Mason, Kayleigh J; O'Neill, Terence W; Lunt, Mark; Jones, Anthony K P; McBeth, John

2018-01-26

helplessness) and illness perceptions (consequences and concern) were significant partial mediators of the association with global pain intensity when loaded on to a latent mediator for: tender point count [75% total effect; 95% confidence interval (CI) 22%, 100%]; MPS at the knee (49%; 12%, 86%); and DMA at the knee (63%; 5%, 100%). Latent psychosocial factors were also significant partial mediators of the association between pain intensity at the tested knee with MPS at the knee (30%; 2%, 58%), but not for DMA at the knee. Measures of mechanical hyperalgesia at the most painful knee and pain-free opposite forearm were associated with increased knee and global pain indicative of altered central processing. Psychosocial factors were significant partial mediators, highlighting the importance of the central integration of emotional processing in pain perception. Associations between mechanical hyperalgesia at the forearm and knee, psychosocial factors and increased levels of clinical global and knee pain intensity provide evidence of altered central processing as a key mechanism in knee pain, with psychological factors playing a key role in the expression of clinical pain.

Anti-hyperalgesic and anti-inflammatory effects of Achillea santolina and Stachys athorecalyx extracts on complete Freund's adjuvant–induced short- term inflammation in male wistar rats

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Elaheh Tekieh

2011-04-01

Full Text Available Introduction: Immune system is involved in the etiology and path physiologic mechanisms of inflammation. Medicinal plants are an important source of substances which are claimed to induce non-specific immune modulator effects. Given the above information and the role of IL-6 in inflammation and pain induction, this study investigated the effects of Achillea santolina and Stachys athorecalyx methanolic and defatted extracts on cmplete Freund's adjuvant (CFA -induced short term inflammation in male Wistar rats Materials and Methods: Inflammation was induced on day zero by CFA injection in hind paw of rats. Methanolic and defatted extractions were prepared form aerial parts of both plants. 50, 100 and 200 mg/kg doses of extracts were selected for IP treatment during 6 days after CFA injection. Results: Results indicated dose related effects of A. santolina and S. athorecalyx extracts on edema, hyperalgesia and serum IL-6 level during inflammation. Although, both methanolic and defatted extracts of S. athorecalyx showed a significant reduction in the inflammatory symptoms, no significant differences was observed between these two kinds of extracts of S.athorecalyx with respect to their anti inflammatory effects. Only methanolic extract of A. santolina was effective during CFA-induced inflammation. Conclusion: These results could suggest that short-term administration of A. santolina and S. athorecalyx extracts possess potent anti-inflammatory effects and modulate paw edema, hyperalgesia and serum IL-6 level during CFA–induced inflammation. In addition, these dose-dependent effects may mediate via different extract supplements which need more investigations.

Postoperative MRI of the ankle

International Nuclear Information System (INIS)

Sharabianlou Korth, M.; Fritz, L.B.