The prevalence of fibromyalgia in other chronic pain conditions.

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Yunus, Muhammad B

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

Fast Green FCF Alleviates Pain Hypersensitivity and Down-Regulates the Levels of Spinal P2X4 Expression and Pro-inflammatory Cytokines in a Rodent Inflammatory Pain Model

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Fang Xu

2018-05-01

Full Text Available Fast Green FCF (FGF, a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund’s adjuvant (CFA and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, and interleukin-6 (IL-6], but did not alter the spinal level of nerve growth factor (NGF or brain-derived neurotrophic factor (BDNF. In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

The role of glia in the spinal cord in neuropathic and inflammatory pain.

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Old, Elizabeth Amy; Clark, Anna K; Malcangio, Marzia

2015-01-01

Chronic pain, both inflammatory and neuropathic, is a debilitating condition in which the pain experience persists after the painful stimulus has resolved. The efficacy of current treatment strategies using opioids, NSAIDS and anticonvulsants is limited by the extensive side effects observed in patients, underlining the necessity for novel therapeutic targets. Preclinical models of chronic pain have recently provided evidence for a critical role played by glial cells in the mechanisms underlying the chronicity of pain, both at the site of damage in the periphery and in the dorsal horn of the spinal cord. Here microglia and astrocytes respond to the increased input from the periphery and change morphology, increase in number and release pro-nociceptive mediators such as ATP, cytokines and chemokines. These gliotransmitters can sensitise neurons by activation of their cognate receptors thereby contributing to central sensitization which is fundamental for the generation of allodynia, hyperalgesia and spontaneous pain.

Neural control disturbances of the gastrointestinal tract and visceral pain in inflammatory bowel diseases 

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Katarzyna Ciesielczyk

2013-04-01

Full Text Available Inflammatory bowel disease (IBD is a chronic intestinal inflammatory condition, the etiology of which is composed of factors such as the environment, genetic predisposition, gut dysbiosis and inadequate immune response. The pathologic findings in Crohn’s disease and ulcerative colitis are related to dysfunction of gastrointestinal secretion and motility and also disturbed visceral sensory function, with accompanying intestinal and parenteral complications. The systemic inflammatory response affects neurological control via the gut-brain axis, which modulates the cooperation of the autonomic nervous system (ANS, enteric nervous system (ENS and gut-associated lymphoid tissue (GALT. In chronic inflammation the intestinal neuropathy disrupts peristalsis and intestinal secretion as well as causing unpleasant symptoms of the patients. Pain receptors are stimulated by inflammatory mediators, and due to the intensified activation of the nociceptive system visceral hypersensitivity through central and peripheral sensitization is generated. Chronic visceral pain negatively influences the course of disease and the quality of the patient’s life. The growing knowledge about the neurological control dysfunction of the intestine and immune system dysregulation could provide proper directives for treatment of inflammatory bowel diseases.

Koumine Attenuates Neuroglia Activation and Inflammatory Response to Neuropathic Pain

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Gui-Lin Jin

2018-01-01

Full Text Available Despite decades of studies, the currently available drugs largely fail to control neuropathic pain. Koumine—an alkaloidal constituent derived from the medicinal plant Gelsemium elegans Benth.—has been shown to possess analgesic and anti-inflammatory properties; however, the underlying mechanisms remain unclear. In this study, we aimed to investigate the analgesic and anti-inflammatory effects and the possible underlying mechanisms of koumine. The analgesic and anti-inflammatory effects of koumine were explored by using chronic constriction injury of the sciatic nerve (CCI neuropathic pain model in vivo and LPS-induced injury in microglia BV2 cells in vitro. Immunofluorescence staining and Western blot analysis were used to assess the modulator effect of koumine on microglia and astrocyte activation after CCI surgery. Enzyme-linked immunosorbent assay (ELISA was used to evaluate the levels of proinflammatory cytokines. Western blot analysis and quantitative real-time polymerase chain reaction (qPCR were used to examine the modulator effect of koumine on microglial M1 polarization. We found that single or repeated treatment of koumine can significantly reduce neuropathic pain after nerve injury. Moreover, koumine showed inhibitory effects on CCI-evoked microglia and astrocyte activation and reduced proinflammatory cytokine production in the spinal cord in rat CCI models. In BV2 cells, koumine significantly inhibited microglia M1 polarization. Furthermore, the analgesic effect of koumine was inhibited by a TSPO antagonist PK11195. These findings suggest that the analgesic effects of koumine on CCI-induced neuropathic pain may result from the inhibition of microglia activation and M1 polarization as well as the activation of astrocytes while sparing the anti-inflammatory responses to neuropathic pain.

Protective Effects of Sinomenine on CFA-Induced Inflammatory Pain in Rats.

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Yuan, Yan; Zhang, Yongjun; He, Xiaofeng; Fan, Shengdeng

2018-04-05

BACKGROUND The purpose of this study was to investigate the effects of sinomenine (SIN) on CFA-induced inflammatory pain in rats, and to explore the underlying molecular mechanisms. MATERIAL AND METHODS To determine the potential influences of SIN in the pathogenesis of inflammatory pain, an inflammatory pain (IP) mouse model was established and rats were treated with SIN (30 mg/kg). Behavioral tests were used to assess the MWT and TWL of the rats. ELISA assay was used to detect the level of inflammation cytokines. Western blotting and qRT-PCR were carried out to measure the related protein and mRNA expression level, respectively. RESULTS We found that the MWT and TWL of the CFA-treated rats were markedly lower than that of the control rats, and they were significantly increased by SIN administration. The results suggest that IP rats had higher levels of TNF-α, IL-1β and IL-6 compared with the control rats. SIN administration decreased the levels of TNF-α, IL-1β, and IL-6. In addition, we found that p-p65 and p-p38 expression notably decreased after SIN treatment in IP rats. Moreover, the results showed that SIN inhibited Cox-2 and PGE2 expression in IP rats. CONCLUSIONS The data indicate that SIN had a protective role in inflammatory pain through repressing inflammatory mediators via preventing the p38MAPK-NF-κB pathway.

Attenuation of TRPV1 and TRPV4 Expression and Function in Mouse Inflammatory Pain Models Using Electroacupuncture

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Wei-Hsin Chen

2012-01-01

Full Text Available Although pain is a major human affliction, our understanding of pain mechanisms is limited. TRPV1 (transient receptor potential vanilloid subtype 1 and TRPV4 are two crucial receptors involved in inflammatory pain, but their roles in EA- (electroacupuncture- mediated analgesia are unknown. We injected mice with carrageenan (carra or a complete Freund’s adjuvant (CFA to model inflammatory pain and investigated the analgesic effect of EA using animal behavior tests, immunostaining, Western blotting, and a whole-cell recording technique. The inflammatory pain model mice developed both mechanical and thermal hyperalgesia. Notably, EA at the ST36 acupoint reversed these phenomena, indicating its curative effect in inflammatory pain. The protein levels of TRPV1 and TRPV4 in DRG (dorsal root ganglion neurons were both increased at day 4 after the initiation of inflammatory pain and were attenuated by EA, as demonstrated by immunostaining and Western blot analysis. We verified DRG electrophysiological properties to confirm that EA ameliorated peripheral nerve hyperexcitation. Our results indicated that the AP (action potential threshold, rise time, and fall time, and the percentage and amplitude of TRPV1 and TRPV4 were altered by EA, indicating that EA has an antinociceptive role in inflammatory pain. Our results demonstrate a novel role for EA in regulating TRPV1 and TRPV4 protein expression and nerve excitation in mouse inflammatory pain models.

Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

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Rijnierse, Anneke

2006-01-01

The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

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Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

2014-01-01

To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice

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Serena Boccella

2015-01-01

Full Text Available D-Aspartate (D-Asp is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO. D-Asp acts as an agonist on NMDA receptors (NMDARs. Accordingly, high levels of D-Asp in knockout mice for Ddo gene (Ddo−/− or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated in Ddo−/− mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found that Ddo−/− mice show an increased evoked activity of the nociceptive specific (NS neurons of the dorsal horn of the spinal cord (L4–L6 and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover, Ddo gene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.

Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

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Jun Yang

2017-01-01

Full Text Available Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1 is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG and spinal cord (SC at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB and nociceptive ion channels (Nav1.7 and Nav1.8 were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Low-Dose Tramadol and Non-Steroidal Anti-Inflammatory Drug Combination Therapy Prevents the Transition to Chronic Low Back Pain.

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Inage, Kazuhide; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Sakuma, Yoshihiro; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Inoue, Masahiro; Kinoshita, Hideyuki; Takahashi, Kazuhisa; Ohtori, Seiji

2016-08-01

Retrospective study. To determine whether low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy could prevent the transition of acute low back pain to chronic low back pain. Inadequately treated early low back pain transitions to chronic low back pain occur in approximately 30% of affected individuals. The administration of non-steroidal anti-inflammatory drugs is effective for treatment of low back pain in the early stages. However, the treatment of low back pain that is resistant to non-steroidal anti-inflammatory drugs is challenging. Patients who presented with acute low back pain at our hospital were considered for inclusion in this study. After the diagnosis of acute low back pain, non-steroidal anti-inflammatory drug administration was started. Forty patients with a visual analog scale score of >5 for low back pain 1 month after treatment were finally enrolled. The first 20 patients were included in a non-steroidal anti-inflammatory drug group, and they continued non-steroidal anti-inflammatory drug therapy for 1 month. The next 20 patients were included in a combination group, and they received low-dose tramadol plus non-steroidal anti-inflammatory drug combination therapy for 1 month. The incidence of adverse events and the improvement in the visual analog scale score at 2 months after the start of treatment were analyzed. No adverse events were observed in the non-steroidal anti-inflammatory drug group. In the combination group, administration was discontinued in 2 patients (10%) due to adverse events immediately following the start of tramadol administration. At 2 months, the improvement in the visual analog scale score was greater in the combination group than in the non-steroidal anti-inflammatory drug group (ppain to chronic low back pain.

Contribution of microglia and astrocytes to the central sensitization, inflammatory and neuropathic pain in the juvenile rat

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Ikeda Hiroshi

2012-06-01

Full Text Available Abstract Background The development of pain after peripheral nerve and tissue injury involves not only neuronal pathways but also immune cells and glia. Central sensitization is thought to be a mechanism for such persistent pain, and ATP involves in the process. We examined the contribution of glia to neuronal excitation in the juvenile rat spinal dorsal horn which is subjected to neuropathic and inflammatory pain. Results In rats subjected to neuropathic pain, immunoreactivity for the microglial marker OX42 was markedly increased. In contrast, in rats subjected to inflammatory pain, immunoreactivity for the astrocyte marker glial fibrillary acidic protein was increased slightly. Optically-recorded neuronal excitation induced by single-pulse stimulation to the dorsal root was augmented in rats subjected to neuropathic and inflammatory pain compared to control rats. The bath application of a glial inhibitor minocycline and a p38 mitogen-activated protein kinase inhibitor SB203580 inhibited the neuronal excitation in rats subjected to neuropathic pain. A specific P2X1,2,3,4 antagonist TNP-ATP largely inhibited the neuronal excitation only in rats subjected to neuropathic pain rats. In contrast, an astroglial toxin L-alpha-aminoadipate, a gap junction blocker carbenoxolone and c-Jun N-terminal kinase inhibitor SP600125 inhibited the neuronal excitation only in rats subjected to inflammatory pain. A greater number of cells in spinal cord slices from rats subjected to neuropathic pain showed Ca2+ signaling in response to puff application of ATP. This Ca2+ signaling was inhibited by minocycline and TNP-ATP. Conclusions These results directly support the notion that microglia is more involved in neuropathic pain and astrocyte in inflammatory pain.

Persistent facial pain conditions

DEFF Research Database (Denmark)

Forssell, Heli; Alstergren, Per; Bakke, Merete

2016-01-01

Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

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Krzyzanowska, Agnieszka; Avendaño, Carlos

2012-01-01

Orofacial pain conditions are often very debilitating to the patient and difficult to treat. While clinical interest is high, the proportion of studies performed in the orofacial region in laboratory animals is relatively low, compared with other body regions. This is partly due to difficulties in testing freely moving animals and therefore lack of reliable testing methods. Here we present a comprehensive review of the currently used rodent models of inflammatory and neuropathic pain adapted to the orofacial areas, taking into account the difficulties and drawbacks of the existing approaches. We examine the available testing methods and procedures used for assessing the behavioral responses in the face in both mice and rats and provide a summary of some pharmacological agents used in these paradigms to date. The use of these agents in animal models is also compared with outcomes observed in the clinic. PMID:23139912

Epigenetic suppression of potassium-chloride co-transporter 2 expression in inflammatory pain induced by complete Freund's adjuvant (CFA).

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Lin, C-R; Cheng, J-K; Wu, C-H; Chen, K-H; Liu, C-K

2017-02-01

Multiple mechanisms contribute to the stimulus-evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium-chloride co-transporter 2 (KCC2) gene expression in the persistence of inflammatory pain. Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection. Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock-down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour. These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA. Persistent pain suppresses KCC2 expression through HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of

Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models

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Kanako So

2015-03-01

Full Text Available Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2 in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.

The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

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Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

2009-01-01

Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases.

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Murray W Enns

Full Text Available Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID, depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255, inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154 and a depression and anxiety group (n = 307, using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0. When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5. These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

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Arjun eMuralidharan

2016-05-01

Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy.

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Granovsky, Yelena; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granot, Michal

2017-05-01

Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN). To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients. In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain. Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = -0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group ( P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to "normalize" with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Inflammatory spine disease as a cause of back pain

International Nuclear Information System (INIS)

Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C.

2006-01-01

The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-α antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-α antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [de

Radiological and scintigraphic findings in patients with a clinical history of chronic inflammatory back pain

International Nuclear Information System (INIS)

Goei The, H.S.; Lemmens, A.J.; Goedhard, G.; Lokkerbol, H.; Rahmy, A.; Linden, S.M. van der; Cats, A.; Steven, M.M.

1985-01-01

The prevalence of radiological abnormalities of the sacroiliac joints, the manubriosternal joint, and the lumbar spine were assessed, and quantitative sacroiliac scintigraphy was performed in 151 patients with a history of chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Sacroiliitis was found in 124 patients (82%), manubriosternal lesions in 84 patients (56%), and lesions of the lumbar spine in 58 patients (38%). In 19 patients (13%), manubriosternal lesions provided the sole radiological abnormality and in five patients (3%) no radiological abnormality could be demonstrated at any of these sites. Quantitative sacroiliac scintigraphy showed increased values in 69 of 137 patients examined (50%), but also in 10 out of 12 control patients with disc degeneration (83%) and is, therefore, nonspecific for inflammatory lesions. Radiological examination of the manubriosternal joint is recommended in patients with inflammatory back pain without radiographic evidence of sacroiliitis. (orig.)

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

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Yelena Granovsky

2017-06-01

Conclusion:. Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

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Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

International Nuclear Information System (INIS)

Oliveira, K.G.; Zeidler, S.V. von; Lamas, A.Z.; Podestá, J.R.V. de; Sena, A.; Souza, E.D.; Lenzi, J.; Lemos, E.M.; Gouvea, S.A.; Bissoli, N.S.

2014-01-01

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

Energy Technology Data Exchange (ETDEWEB)

Oliveira, K.G. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Zeidler, S.V. von [Departamento de Patologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Lamas, A.Z. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Podestá, J.R.V. de; Sena, A.; Souza, E.D.; Lenzi, J. [Divisão de Cabeça e Pescoço, Hospital Santa Rita de Cássia, Vitória, ES (Brazil); Lemos, E.M. [Centro de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Gouvea, S.A.; Bissoli, N.S. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

2014-05-30

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.

Cancer Pain Physiology

DEFF Research Database (Denmark)

Falk, Sarah; Bannister, Kirsty; Dickenson, Anthony

2014-01-01

Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells....... This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined...... to the mouse femur. This model prompted related approaches and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer induced bone pain results in progressive bone destruction, elevated osteoclast activity...

Medical conditions and body pain in patients presenting orofacial pain.

Science.gov (United States)

Franco, Ana Lúcia; Runho, Gabriel Henrique Farto; Siqueira, José Tadeu Tesseroli de; Camparis, Cinara Maria

2012-05-01

To verify the frequency of self-reported medical conditions and pain areas in orofacial pain patients, comparing them with patients from the routine dental care. Data were collected from archives of the Orofacial Pain Clinic (Group A, n=319) and of the routine dental care clinics (Group B, n=84) at Faculdade de Odontologia de Araraquara, São Paulo, in Brazil. All individuals answered a standardized clinical questionnaire and completed a body map indicating their pain areas. The Mann-Whitney's test demonstrated that Group A presented a higher mean number of medical reports than Group B (p=0.004). In both groups, Pearson's correlation test showed that the highest frequencies of medical conditions were positively correlated to highest frequencies of painful areas (0.478, p=0.001 and 0.246, p=0.000, respectively). Group A tended to report more medical conditions and there was a positive correlation between the number of medical conditions and the one of pain areas for both groups.

[Peroral and transdermal application of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of regional musculoskeletal pain syndromes].

Science.gov (United States)

Hodinka, László; Bálint, Géza; Budai, Erika; Géher, Pál; Papp, Renáta; Somogyi, Péter; Szántó, Sándor; Vereckei, Edit

2017-12-01

In this review the available evidences regarding the most frequently applied medication (peroral and transdermal non-steroidal anti-inflammatory agents) for the most frequent musculoskeletal complaints (regional pain syndromes) have been collected for the appropriate medical professionals who are most frequently faced with these conditions (general practitioners, rheumatologists, orthopedics, occupational and sports medicine experts). The special population at risk (with repeated and high energy overuse because of occupational or sport activities) and the pathology of their syndromes are identified. Mode of action, pharmacological properties of the non-steroidal anti-inflammatory drugs and the unwanted effects of their application especially in infants and elderly are highlighted. Recommendations of the general and specific pain management guidelines have been selected and listed in the review. Orv Hetil. 2017; 158(Suppl. 3): 3-30.

Differential effects of subcutaneous electrical stimulation (SQS) and transcutaneous electrical nerve stimulation (TENS) in rodent models of chronic neuropathic or inflammatory pain.

Science.gov (United States)

Vera-Portocarrero, Louis P; Cordero, Toni; Billstrom, Tina; Swearingen, Kim; Wacnik, Paul W; Johanek, Lisa M

2013-01-01

Electrical stimulation has been used for many years for the treatment of pain. Present-day research demonstrates that stimulation targets and parameters impact the induction of specific pain-modulating mechanisms. New targets are increasingly being investigated clinically, but the scientific rationale for a particular target is often not well established. This present study compares the behavioral effects of targeting peripheral axons by electrode placement in the subcutaneous space vs. electrode placement on the surface of the skin in a rodent model. Rodent models of inflammatory and neuropathic pain were used to investigate subcutaneous electrical stimulation (SQS) vs. transcutaneous electrical nerve stimulation (TENS). Electrical parameters and relative location of the leads were held constant under each condition. SQS had cumulative antihypersensitivity effects in both inflammatory and neuropathic pain rodent models, with significant inhibition of mechanical hypersensitivity observed on days 3-4 of treatment. In contrast, reduction of thermal hyperalgesia in the inflammatory model was observed during the first four days of treatment with SQS, and reduction of cold allodynia in the neuropathic pain model was seen only on the first day with SQS. TENS was effective in the inflammation model, and in agreement with previous studies, tolerance developed to the antihypersensitivity effects of TENS. With the exception of a reversal of cold hypersensitivity on day 1 of testing, TENS did not reveal significant analgesic effects in the neuropathic pain rodent model. The results presented show that TENS and SQS have different effects that could point to unique biologic mechanisms underlying the analgesic effect of each therapy. Furthermore, this study is the first to demonstrate in an animal model that SQS attenuates neuropathic and inflammatory-induced pain behaviors. © 2013 Medtronic, Inc.

Operant conditioning of facial displays of pain.

Science.gov (United States)

Kunz, Miriam; Rainville, Pierre; Lautenbacher, Stefan

2011-06-01

The operant model of chronic pain posits that nonverbal pain behavior, such as facial expressions, is sensitive to reinforcement, but experimental evidence supporting this assumption is sparse. The aim of the present study was to investigate in a healthy population a) whether facial pain behavior can indeed be operantly conditioned using a discriminative reinforcement schedule to increase and decrease facial pain behavior and b) to what extent these changes affect pain experience indexed by self-ratings. In the experimental group (n = 29), the participants were reinforced every time that they showed pain-indicative facial behavior (up-conditioning) or a neutral expression (down-conditioning) in response to painful heat stimulation. Once facial pain behavior was successfully up- or down-conditioned, respectively (which occurred in 72% of participants), facial pain displays and self-report ratings were assessed. In addition, a control group (n = 11) was used that was yoked to the reinforcement plans of the experimental group. During the conditioning phases, reinforcement led to significant changes in facial pain behavior in the majority of the experimental group (p .136). Fine-grained analyses of facial muscle movements revealed a similar picture. Furthermore, the decline in facial pain displays (as observed during down-conditioning) strongly predicted changes in pain ratings (R(2) = 0.329). These results suggest that a) facial pain displays are sensitive to reinforcement and b) that changes in facial pain displays can affect self-report ratings.

Pain Report and Pain-Related Evoked Potentials Operantly Conditioned

NARCIS (Netherlands)

Lousberg, Richel; Vuurman, Eric; Lamers, Theo; van Breukelen, Gerard; Jongen, Ellen; Rijnen, Heidi; Maessen, Christa; Hermens, Hermanus J.

Objective: The purpose of the present study was to answer the ques- tion whether pain report can be increased and decreased by operant conditioning. We predicted that the conditioned pain effects would remain significant after correction for social desirability and fantasy proneness. Furthermore, we

Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

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

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

DEFF Research Database (Denmark)

Ravn, Pernille; Secher, EL; Skram, U

2013-01-01

Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore...... to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...... pain modulation....

The Anti-Inflammatory Actions of Auricular Point Acupressure for Chronic Low Back Pain

Directory of Open Access Journals (Sweden)

Wei-Chun Lin

2015-01-01

Full Text Available Background. Auricular point acupressure (APA is a promising treatment for pain management. Few studies have investigated the physiological mechanisms of APA analgesics. Method. In this pilot randomized clinical trial (RCT, a 4-week APA treatment was used to manage chronic low back pain (CLBP. Sixty-one participants were randomized into a real APA group (n=32 or a sham APA group (n=29. Blood samples, pain intensity, and physical function were collected at baseline and after 4 weeks of treatment. Results. Subjects in the real APA group reported a 56% reduction of pain intensity and a 26% improvement in physical function. Serum blood samples showed (1 a decrease in IL-1β, IL-2, IL-6, and calcitonin gene-related peptide [CGRP] and (2 an increase in IL-4. In contrast, subjects in the sham APA group (1 reported a 9% reduction in pain and a 2% improvement in physical function and (2 exhibited minimal changes of inflammatory cytokines and neuropeptides. Statistically significant differences in IL-4 and CGRP expression between the real and sham APA groups were verified. Conclusion. These findings suggest that APA treatment affects pain intensity through modulation of the immune system, as reflected by APA-induced changes in serum inflammatory cytokine and neuropeptide levels.

Delineating inflammatory and mechanical sub-types of low back pain: a pilot survey of fifty low back pain patients in a chiropractic setting

Directory of Open Access Journals (Sweden)

Riksman Janine S

2011-02-01

Full Text Available Abstract Background An instrument known as the Mechanical and Inflammatory Low Back Pain (MAIL Scale was drafted using the results of a previous expert opinion study. A pilot survey was conducted to test the feasibility of a larger study designed to determine the MAIL Scale's ability to distinguish two potential subgroups of low back pain: inflammatory and mechanical. Methods Patients with a primary complaint of low back pain (LBP presenting to chiropractic clinics in Perth, Western Australia were asked to fill out the MAIL Scale questionnaire. The instrument's ability to separate patients into inflammatory and mechanical subgroups of LBP was examined using the mean score of each notional subgroup as an arbitrary cut-off point. Results Data were collected from 50 patients. The MAIL Scale did not appear to separate cases of LBP into the two notionally distinct groups of inflammatory (n = 6 or mechanical (n = 5. A larger "mixed symptom" group (n = 39 was revealed. Conclusions In this pilot study the MAIL Scale was unable to clearly discriminate between what is thought to be mechanical and inflammatory LBP in 50 cases seen in a chiropractic setting. However, the small sample size means any conclusions must be viewed with caution. Further research within a larger study population may be warranted and feasible.

Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain.

Science.gov (United States)

Chen, Lei; Liu, Jin-cheng; Zhang, Xiao-nan; Guo, Yan-yan; Xu, Zhao-hui; Cao, Wei; Sun, Xiao-li; Sun, Wen-ji; Zhao, Ming-Gao

2008-06-01

Gentiopicroside is one of the secoiridoid compound isolated from Gentiana lutea. It exhibits analgesic activities in the mice. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACC. But little is known about Gentiopicroside on the persistent inflammatory pain and chronic pain-induced synaptic transmission changes in the ACC. The present study was undertaken to investigate its analgesic activities and central synaptic modulation to the peripheral painful inflammation. Gentiopicroside produced significant analgesic effects against persistent inflammatory pain stimuli in mice. Systemic administration of Gentiopicroside significantly reversed NR2B over-expression during the chronic phases of persistent inflammation caused by hind-paw administration of complete Freunds adjuvant (CFA) in mice. Whole-cell patch clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents in the ACC. Our findings provide strong evidence that analgesic effects of Gentiopicroside involve down-regulation of NR2B receptors in the ACC to persistent inflammatory pain.

Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis.

Science.gov (United States)

Hall, B E; Zhang, L; Sun, Z J; Utreras, E; Prochazkova, M; Cho, A; Terse, A; Arany, P; Dolan, J C; Schmidt, B L; Kulkarni, A B

2016-02-01

Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α(glo)) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α(glo) mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α(glo) mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α(glo) mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain. © International & American Associations for Dental Research 2015.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

Science.gov (United States)

Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

2017-06-01

Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

Science.gov (United States)

Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

2016-08-01

Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating

Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36-ST37 Acupoints on CFA-induced Inflammatory Pain.

Science.gov (United States)

Lu, Kung-Wen; Hsu, Chao-Kuei; Hsieh, Ching-Liang; Yang, Jun; Lin, Yi-Wen

2016-02-24

Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund's adjuvant (CFA), (2.14 ± 0.1, p CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain.

Mechanisms of Acupuncture-Electroacupuncture on Persistent Pain

Science.gov (United States)

Zhang, Ruixin; Lao, Lixing; Ren, Ke; Berman, Brian M.

2014-01-01

In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue-injury (inflammatory), nerve-injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2–10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce pro-inflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal n-methyl-d-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management that can forestall the side effects of often-debilitating pharmaceuticals. PMID:24322588

Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis

DEFF Research Database (Denmark)

Whittle, Samuel L; Colebatch, Alexandra N; Buchbinder, Rachelle

2012-01-01

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA).Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process......, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008-09 European League Against Rheumatism (EULAR...... to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty...

EULAR recommendations for the health professional's approach to pain management in inflammatory arthritis and osteoarthritis

NARCIS (Netherlands)

Geenen, Rinie; Overman, Cécile L; Christensen, Robin; Åsenlöf, Pernilla; Capela, Susana; Huisinga, Karen L; Husebø, Mai Elin P; Köke, Albère J A; Paskins, Zoe; Pitsillidou, Irene A; Savel, Carine; Austin, Judith; Hassett, Afton L; Severijns, Guy; Stoffer-Marx, Michaela; Vlaeyen, Johan W S; Fernández-de-Las-Peñas, César; Ryan, Sarah J; Bergman, Stefan

2018-01-01

Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach to pain management. A multidisciplinary task force including professionals and patient

A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

Directory of Open Access Journals (Sweden)

Yang Qi

2009-12-01

Full Text Available Abstract The midbrain periaqueductal grey (PAG is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp, one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

Therapeutic Efficacy and Tolerability of the Topical Treatment of Inflammatory Conditions of the Oral Cavity with a Mouthwash Containing Diclofenac Epolamine : A Randomized, Investigator-Blind, Parallel-Group, Controlled, Phase III Study.

Science.gov (United States)

Serafini, Giampiero; Trevisan, Silvia; Saponati, Giorgio; Bandettini, Bernardo

2012-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs), including diclofenac, are the mainstay of analgesic and anti-inflammatory treatment in dentistry. Diclofenac epolamine [diclofenac N-(2-hydroxyethyl)pyrrolidine; DHEP] is a diclofenac salt with greater water solubility and better cutaneous absorption properties than other commonly used forms of the drug. IBSA has recently developed a mouthwash formulation of DHEP for the topical treatment of inflammatory conditions of the oral cavity. The aim of this study was to compare the efficacy and tolerability of DHEP mouthwash (Osmal®) with that of a reference product (commercially available diclofenac mouthwash). This was a randomized, investigator-blind, parallel-group, controlled, phase III study that enrolled 80 patients with conditions affecting the oral cavity, characterized by an inflammatory component, and eligible for analgesic and anti-inflammatory treatment. Patients were randomized 1 : 1 to DHEP mouthwash (0.103% DHEP in aqueous solution) or to diclofenac mouthwash (0.074% free diclofenac in aqueous solution). The treatment regimen was the same in both groups: 1-minute rinse with 15 mL of mouthwash, twice daily for 7 days. Visits were scheduled at study inclusion (D0), and 3 days (D3) and 7 days (D7) after treatment initiation. During each visit assessments were made of pain severity (using a 5-point semi-quantitative scale and a 100-mm visual analogue scale [VAS]) and inflammatory signs (using a 5-point scale). The primary study endpoint was the change in pain severity scores from D0 to D3 and D7. Secondary endpoints included effects of treatment on inflammation score, quality of sleep, compliance with treatment and the safety and tolerability of treatment. The two treatment arms were homogeneous in terms of patient characteristics. The most prevalent oral condition was gingivitis. Overall both topical treatments were effective in alleviating pain and inflammation, as evidenced by decreases in pain and

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

Science.gov (United States)

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

Conditioned pain modulation in patients with nonspecific chronic back pain with chronic local pain, chronic widespread pain, and fibromyalgia.

Science.gov (United States)

Gerhardt, Andreas; Eich, Wolfgang; Treede, Rolf-Detlef; Tesarz, Jonas

2017-03-01

Findings considering conditioned pain modulation (CPM) in chronic back pain (CBP) are contradictory. This might be because many patients with CBP report pain in further areas of the body, and altered CPM might influence spatial extent of pain rather than CBP per se. Therefore, we compared CPM in patients with CBP with different pain extent. Patients with fibromyalgia syndrome (FMS), for whom CPM impairment is reported most consistently, were measured for comparison. Based on clinical evaluation and pain drawings, patients were categorized into chronic local back pain (CLP; n = 53), chronic widespread back pain (CWP; n = 32), and FMS (n = 92). Conditioned pain modulation was measured by the difference in pressure pain threshold (test stimuli) at the lower back before and after tonic heat pain (conditioning stimulus). We also measured psychosocial variables. Pressure pain threshold was significantly increased in CLP patients after tonic heat pain (P pain modulation in CLP was significantly higher than that in CWP and FMS (P painful areas (0-10) were associated with lower CPM (r = 0.346, P = 0.001) in CBP but not in FMS (r = -0.013, P = 0.903). Anxiety and depression were more pronounced in FMS than in CLP or CWP (P values pain inhibition seem to be more indicated the higher the pain extent.

Human psychophysics and rodent spinal neurones exhibit peripheral and central mechanisms of inflammatory pain in the UVB and UVB heat rekindling models.

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O'Neill, Jessica; Sikandar, Shafaq; McMahon, Stephen B; Dickenson, Anthony H

2015-09-01

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of

A psychophysical study of endogenous analgesia: the role of the conditioning pain in the induction and magnitude of conditioned pain modulation.

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Nir, Rony-Reuven; Granovsky, Yelena; Yarnitsky, David; Sprecher, Elliot; Granot, Michal

2011-05-01

Endogenous analgesia (EA) can be examined experimentally using a conditioned pain modulation (CPM) paradigm. While noxious conditioning stimulation intensities (CSIs) are mainly used, it has not been fully investigated in the same experimental design whether the experienced conditioning pain level affects CPM responses. The principal goal of the present study was to characterize CPM induction and magnitudes evoked by various conditioning pain levels. Furthermore, we explored associations between conditioning pain reports and CPM responses across various CSIs. Thirty healthy, young, right-handed males were tested with a parallel CPM paradigm. Three different CSIs (hand water-immersion) induced mild, moderate and intense pain levels, rated 12.41 ± 7.85, 31.57 ± 9.56 and 58.1 ± 11.43, respectively (0-100 numerical pain scale) (P < 0.0001). Contact-heat 'test-stimulus' levels were compared before and during conditioning. Within the group, (i) CPM was induced only by the moderate and intense CSIs (Ps ≤ 0.001); (ii) no difference was demonstrated between the magnitudes of these CPM responses. Regression analysis revealed that CPM induction was independent of the perceived conditioning pain level, but associated with the absolute CSI (P < 0.0001). Conditioning pain levels were correlated across all CSIs, as were CPM magnitudes (Ps ≤ 0.01). We conclude that among males, (i) once a CPM response is evoked by a required conditioning pain experience, its magnitude is not further affected by increasing conditioning pain and (ii) CPM magnitudes are inter-correlated, but unrelated to conditioning pain reports. These observations may suggest that CPM responses represent an intrinsic element of an individual's EA processes, which are not significantly affected by the experienced conditioning pain. Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

Anti-inflammatory actions of acupuncture

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Freek J. Zijlstra

2003-01-01

Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

Acid-sensing ion channels in trigeminal ganglion neurons innervating the orofacial region contribute to orofacial inflammatory pain.

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Fu, Hui; Fang, Peng; Zhou, Hai-Yun; Zhou, Jun; Yu, Xiao-Wei; Ni, Ming; Zheng, Jie-Yan; Jin, You; Chen, Jian-Guo; Wang, Fang; Hu, Zhuang-Li

2016-02-01

Orofacial pain is a common clinical symptom that is accompanied by tooth pain, migraine and gingivitis. Accumulating evidence suggests that acid-sensing ion channels (ASICs), especially ASIC3, can profoundly affect the physiological properties of nociception in peripheral sensory neurons. The aim of this study is to examine the contribution of ASICs in trigeminal ganglion (TG) neurons to orofacial inflammatory pain. A Western blot (WB), immunofluorescence assay of labelled trigeminal ganglion neurons, orofacial formalin test, cell preparation and electrophysiological experiments are performed. This study demonstrated that ASIC1, ASIC2a and ASIC3 are highly expressed in TG neurons innervating the orofacial region of rats. The amplitude of ASIC currents in these neurons increased 119.72% (for ASIC1-like current) and 230.59% (for ASIC3-like current) in the formalin-induced orofacial inflammatory pain model. In addition, WB and immunofluorescence assay demonstrated a significantly augmented expression of ASICs in orofacial TG neurons during orofacial inflammation compared with the control group. The relative protein density of ASIC1, ASIC2a and ASIC3 also increased 58.82 ± 8.92%, 45.30 ± 11.42% and 55.32 ± 14.71%, respectively, compared with the control group. Furthermore, pharmacological blockade of ASICs and genetic deletion of ASIC1 attenuated the inflammation response. These findings indicate that peripheral inflammation can induce the upregulation of ASICs in TG neurons, causing orofacial inflammatory pain. Additionally, the specific inhibitor of ASICs may have a significant analgesic effect on orofacial inflammatory pain. © 2016 John Wiley & Sons Australia, Ltd.

Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats.

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

2013-03-22

Previous studies have demonstrated that p38 MAPK signal transduction pathway plays an important role in the development and maintenance of inflammatory pain. Electroacupuncture (EA) can suppress the inflammatory pain. However, the relationship between EA effect and p38 MAPK signal transduction pathway in inflammatory pain remains poorly understood. It is our hypothesis that p38 MAPK/ATF-2/VR-1 and/or p38 MAPK/ATF-2/COX-2 signal transduction pathway should be activated by inflammatory pain in CFA-injected model. Meanwhile, EA may inhibit the activation of p38 MAPK signal transduction pathway. The present study aims to investigate that anti-inflammatory and analgesic effect of EA and its intervention on the p38 MAPK signal transduction pathway in a rat model of inflammatory pain. EA had a pronounced anti-inflammatory and analgesic effect on CFA-induced chronic inflammatory pain in rats. EA could quickly raise CFA-rat's paw withdrawal thresholds (PWTs) and maintain good and long analgesic effect, while it subdued the ankle swelling of CFA rats only at postinjection day 14. EA could down-regulate the protein expressions of p-p38 MAPK and p-ATF-2, reduced the numbers of p-p38 MAPK-IR cells and p-ATF-2-IR cells in spinal dorsal horn in CFA rats, inhibited the expressions of both protein and mRNA of VR-1, but had no effect on the COX-2 mRNA expression. The present study indicates that inhibiting the activation of spinal p38 MAPK/ATF-2/VR-1 pathway may be one of the main mechanisms via central signal transduction pathway in the process of anti-inflammatory pain by EA in CFA rats.

Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.

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Cardoso-Cruz, Helder; Sousa, Mafalda; Vieira, Joana B; Lima, Deolinda; Galhardo, Vasco

2013-11-01

The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

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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.

Incidence and impact of pain conditions and comorbid illnesses

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Davis JA

2011-10-01

Full Text Available Jessica A Davis, Rebecca L Robinson, Trong Kim Le, Jin XieLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USABackground: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007.Methods: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period.Results: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine to 2.65 (for multiple sclerosis pain. High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78% and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%, respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome to 11.59% (for multiple sclerosis pain. Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer

Pain management in patients with inflammatory bowel disease: insights for the clinician

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Srinath, Arvind Iyengar; Walter, Chelsea; Newara, Melissa C.

2012-01-01

Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) and has a profound negative impact on patients’ lives. There are growing data suggesting that pain is variably related to the degree of active inflammation. Given the multifactorial etiologies underlying the pain, the treatment of abdominal pain in the IBD population is best accomplished by individualized plans. This review covers four clinically relevant categories of abdominal pain in patients with IBD, namely, inflammation, surgical complications, bacterial overgrowth, and neurobiological processes and how pain management can be addressed in each of these cases. The role of genetic factors, psychological factors, and psychosocial stress in pain perception and treatment will also be addressed. Lastly, psychosocial, pharmacological, and procedural pain management techniques will be discussed. An extensive review of the existing literature reveals a paucity of data regarding pain management specific to IBD. In addition, there is growing consensus suggesting a spectrum between IBD and irritable bowel syndrome (IBS) symptoms. Thus, this review for adult and pediatric clinicians also incorporates the literature for the treatment of functional abdominal pain and the clinical consensus from IBD and IBS experts on pharmacological, behavioral, and procedural methods to treat abdominal pain in this population. PMID:22973418

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

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Bo Hu

2018-05-01

Full Text Available Background/Aims: Paeoniflorin (PF is known to have anti-inflammatory and paregoric effects, but the mechanism underlying its analgesic effect remains unclear. The aim of this study was to clarify the effect of PF on Freund’s complete adjuvant (CFA-induced inflammatory pain and explore the underlying molecular mechanism. Methods: An inflammatory pain model was established by intraplantar injection of CFA in C57BL/6J mice. After intrathecal injection of PF daily for 8 consecutive days, thermal and mechanical withdrawal thresholds, the levels of inflammatory factors TNF-α, IL-1β and IL-6, microglial activity, and the expression of Akt-NF-κB signaling pathway in the spinal cord tissue were detected by animal ethological test, cell culture, enzyme-linked immunosorbent assay, immunofluorescence histochemistry, and western blot. Results: PF inhibited the spinal microglial activation in the CFA-induced pain model. The production of proinflammatory cytokines was decreased in the central nervous system after PF treatment both in vivo and in vitro. PF further displayed a remarkable effect on inhibiting the activation of Akt-NF-κB signaling pathway in vivo and in vitro. Conclusion: These results suggest that PF is a potential therapeutic agent for inflammatory pain and merits further investigation.

Effect of nonsteroidal anti-inflammatory drugs on colorectal distension-induced visceral pain

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Baskın, Veysel; Bilge, S. Sırrı; Bozkurt, Ayhan; Akyüz, Bahar; Ağrı, Arzu Erdal; Güzel, Hasan; İlkaya, Fatih

2016-01-01

Objectives: To investigate nonsteroidal anti-inflammatory drugs effectiveness in colorectal distension (CRD)-induced visceral pain model. Materials and Methods: Male Sprague–Dawley (250–300 g) rats were anesthetized with ketamine (50 mg/kg, intraperitoneally [i.p.]) and chlorpromazine (25 mg/kg, i.p.). Two bipolar Teflon-coated Ni/Cr wire electrodes (80-M diameter) were placed in the abdominal external oblique muscle for the recording of electromyography. Jugular vein catheter was placed for the administration of drugs. CRD method was applied to evaluate of visceral pain. All drugs (paracetamol, meloxicam, metamizole, and dexketoprofen) administered intravenously. Results: Paracetamol 200, 400, and 600 mg/kg did not change the visceromotor response (VMR) when compare with the control group. Meloxicam 2 and 4 mg/kg showed no effect but at doses of 6 mg/kg meloxicam significantly ([51.9 ± 6.4%] [P Dexketoprofen 2 and 4 mg/kg did not cause a change in VMR but 6 mg/kg dose significantly reduced response compared with the control group ([43.9 ± 3.9%, 36.8 ± 2.8%, 34.8 ± 2.5%, 42.1 ± 4.8%, 40.7 ± 3.5%, 36.4 ± 2.7%, and 26.1 ± 2.2%]; from 10 min to 70 min, respectively, [P dexketoprofen and meloxicam show antinociceptive effect with different duration of action on CRD-induced visceral pain model. This condition can be explained due to different chemical structures and different mechanisms which play a role in modulation of pain. PMID:27114637

The Effect of Electroacupuncture on PKMzeta in the ACC in Regulating Anxiety-Like Behaviors in Rats Experiencing Chronic Inflammatory Pain

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Junying Du

2017-01-01

Full Text Available Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC. We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560, PKMzeta, p-PKMzeta (T560, and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560 in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.

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.

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.

Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

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Cui Guang-bin

2012-02-01

Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain.

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Suardíaz, Margarita; Estivill-Torrús, Guillermo; Goicoechea, Carlos; Bilbao, Ainhoa; Rodríguez de Fonseca, Fernando

2007-12-15

Oleoylethanolamide (OEA) is a natural fatty acid amide that mainly modulates feeding and energy homeostasis by binding to peroxisome proliferator-activated receptor-alpha (PPAR-alpha) [Rodríguez de Fonseca F, Navarro M, Gómez R, Escuredo L, Navas F, Fu J, et al. An anorexic lipid mediator regulated by feeding. Nature 2001;414:209-12; Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodríguez de Fonseca F, et al. Oleoylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003;425:90-3]. Additionally, it has been proposed that OEA could act via other receptors, including the vanilloid receptor (TRPV1) [Wang X, Miyares RL, Ahern GP. Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol 2005;564:541-7.] or the GPR119 receptor [Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006;3:167-175], suggesting that OEA might subserve other physiological roles, including pain perception. We have evaluated the effect of OEA in two types of nociceptive responses evoked by visceral and inflammatory pain in rodents. Our results suggest that OEA has analgesic properties reducing the nociceptive responses produced by administration of acetic acid and formalin in two experimental animal models. Additional research was performed to investigate the mechanisms underlying this analgesic effect. To this end, we evaluated the actions of OEA in mice null for the PPAR-alpha receptor gene and compared its actions with those of PPAR-alpha receptor wild-type animal. We also compared the effect of MK-801 in order to evaluate the role of NMDA receptor in this analgesia. Our data showed that OEA reduced visceral and inflammatory responses through a PPAR

Enhanced Gamma Oscillatory Activity in Rats with Chronic Inflammatory Pain

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Wang, Jing; Wang, Jing; Xing, Guo-Gang; Li, Xiaoli; Wan, You

2016-01-01

It has been reported that oscillatory gamma activity participates in brief acute pain and tonic ongoing pain. It is of great interest to determine whether the gamma activity is involved in chronic pain since chronic pain is a more severe pathological condition characterized by pain persistency. To investigate the oscillatory gamma activity in chronic pain, in the present study, we recorded spontaneous electrocorticogram (ECoG) signals during chronic pain development in rats with chronic infla...

VIPER: Chronic Pain after Amputation: Inflammatory Mechanisms, Novel Analgesic Pathways, and Improved Patient Safety

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2016-10-01

Whitney U test for evaluating differences in inflammatory mediators between groups (Case vs. Control) and used nonparametric correlations (Spearman’s rho...responses to acute pain. PAIN 2008;140:135–144. [10] Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions...Concentrations in Cases vs. Controls. Mediator Case (n=36) Median (Range) Control (n=40) Median (Range) Mann- Whitney U Test (p value) IFN

Conditioned pain modulation and situational pain catastrophizing as preoperative predictors of pain following chest wall surgery: a prospective observational cohort study.

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Kasper Grosen

Full Text Available Variability in patients' postoperative pain experience and response to treatment challenges effective pain management. Variability in pain reflects individual differences in inhibitory pain modulation and psychological sensitivity, which in turn may be clinically relevant for the disposition to acquire pain. The aim of this study was to investigate the effects of conditioned pain modulation and situational pain catastrophizing on postoperative pain and pain persistency.Preoperatively, 42 healthy males undergoing funnel chest surgery completed the Spielberger's State-Trait Anxiety Inventory and Beck's Depression Inventory before undergoing a sequential conditioned pain modulation paradigm. Subsequently, the Pain Catastrophizing Scale was introduced and patients were instructed to reference the conditioning pain while answering. Ratings of movement-evoked pain and consumption of morphine equivalents were obtained during postoperative days 2-5. Pain was reevaluated at six months postoperatively.Patients reporting persistent pain at six months follow-up (n = 15 were not significantly different from pain-free patients (n = 16 concerning preoperative conditioned pain modulation response (Z = 1.0, P = 0.3 or level of catastrophizing (Z = 0.4, P = 1.0. In the acute postoperative phase, situational pain catastrophizing predicted movement-evoked pain, independently of anxiety and depression (β = 1.0, P = 0.007 whereas conditioned pain modulation predicted morphine consumption (β = -0.005, P = 0.001.Preoperative conditioned pain modulation and situational pain catastrophizing were not associated with the development of persistent postoperative pain following funnel chest repair. Secondary outcome analyses indicated that conditioned pain modulation predicted morphine consumption and situational pain catastrophizing predicted movement-evoked pain intensity in the acute postoperative phase. These findings may have

Evoked potentials after painful cutaneous electrical stimulation depict pain relief during a conditioned pain modulation.

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Höffken, Oliver; Özgül, Özüm S; Enax-Krumova, Elena K; Tegenthoff, Martin; Maier, Christoph

2017-08-29

Conditioned pain modulation (CPM) evaluates the pain modulating effect of a noxious conditioning stimulus (CS) on another noxious test stimulus (TS), mostly based solely on subjective pain ratings. We used painful cutaneous electrical stimulation (PCES) to induce TS in a novel CPM-model. Additionally, to evaluate a more objective parameter, we recorded the corresponding changes of cortical evoked potentials (PCES-EP). We examined the CPM-effect in 17 healthy subjects in a randomized controlled cross-over design during immersion of the non-dominant hand into 10 °C or 24 °C cold water (CS). Using three custom-built concentric surface electrodes, electrical stimuli were applied on the dominant hand, inducing pain of 40-60 on NRS 0-100 (TS). At baseline, during and after CS we assessed the electrically induced pain intensity and electrically evoked potentials recorded over the central electrode (Cz). Only in the 10 °C-condition, both pain (52.6 ± 4.4 (baseline) vs. 30.3 ± 12.5 (during CS)) and amplitudes of PCES-EP (42.1 ± 13.4 μV (baseline) vs. 28.7 ± 10.5 μV (during CS)) attenuated during CS and recovered there after (all p pain ratings during electrical stimulation and amplitudes of PCES-EP correlated significantly with each other (r = 0.5) and with CS pain intensity (r = 0.5). PCES-EPs are a quantitative measure of pain relief, as changes in the electrophysiological response are paralleled by a consistent decrease in subjective pain ratings. This novel CPM paradigm is a feasible method, which could help to evaluate the function of the endogenous pain modulation processes. German Clinical Trials Register DRKS-ID: DRKS00012779 , retrospectively registered on 24 July 2017.

Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

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Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

2012-09-01

Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

Wu-Tou Decoction Inhibits Chronic Inflammatory Pain in Mice: Participation of TRPV1 and TRPA1 Ion Channels

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Chao Wang

2015-01-01

Full Text Available Wu-tou decoction (WTD is a classic traditional Chinese medicine formula and has been used effectively to treat joint diseases clinically. Previous reports indicated that WTD possesses anti-inflammatory activity; however, its actions on pain have not been clarified. Here, we investigated the antinociceptive activity of WTD in CFA-induced mice, and its possible mechanism of the action associated with transient receptor potential (TRP ion channels was also explored. Our results showed that 1.58, 3.15, and 6.30 g/kg WTD significantly attenuated mechanical, cold, and heat hypersensitivities. Moreover, WTD effectively inhibited spontaneous nociceptive responses to intraplantar injections of capsaicin and cinnamaldehyde, respectively. WTD also effectively suppressed jumping and wet-dog-shake behaviors to intraperitoneal injection of icilin. Additionally, WTD significantly reduced protein expression of TRPV1 and TRPA1 in dorsal root ganglia and skins of injured paw. Collectively, our data demonstrate firstly that WTD exerts antinociceptive activity in inflammatory conditions by attenuating mechanical, cold, and heat hypersensitivities. This antinociceptive effect may result in part from inhibiting the activities of TRPV1, TRPA1, and TRPM8, and the suppression of TRPV1 and TRPA1 protein by WTD was also highly effective. These findings suggest that WTD might be an attractive and suitable therapeutic agent for the management of chronic inflammatory pain.

TREATMENT OF ACUTE INFLAMMATORY DISEASES ACCOMPANIED BY THROAT IRRITATION AND PAIN

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M. I. Petrovskaya

2013-01-01

Full Text Available Pathogenetically, prescription of local action drugs containing a wide spectrum antiseptic is reasonable for the upper respiratory tract diseases accompanied by throat irritation and pain. It should be noted that such drugs are very popular among parents; however, most of these drugs may have a range of side effects, which considerably complicate their use in children. That is why the right choice of local action drugs for the acute inflammatory diseases accompanied by throat irritation and pain is a guarantee of treatment efficacy and high compliance. This article examines pharmacological qualities of an antiseptic-containing local action drug permitted to use in children over 4 years of age.

Fixed or adapted conditioning intensity for repeated conditioned pain modulation.

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Hoegh, M; Petersen, K K; Graven-Nielsen, T

2017-12-29

Aims Conditioned pain modulation (CPM) is used to assess descending pain modulation through a test stimulation (TS) and a conditioning stimulation (CS). Due to potential carry-over effects, sequential CPM paradigms might alter the intensity of the CS, which potentially can alter the CPM-effect. This study aimed to investigate the difference between a fixed and adaptive CS intensity on CPM-effect. Methods On the dominant leg of 20 healthy subjects the cuff pressure detection threshold (PDT) was recorded as TS and the pain tolerance threshold (PTT) was assessed on the non-dominant leg for estimating the CS. The difference in PDT before and during CS defined the CPM-effect. The CPM-effect was assessed four times using a CS with intensities of 70% of baseline PTT (fixed) or 70% of PTT measured throughout the session (adaptive). Pain intensity of the conditioning stimulus was assessed on a numeric rating scale (NRS). Data were analyzed with repeated-measures ANOVA. Results No difference was found comparing the four PDTs assessed before CSs for the fixed and the adaptive paradigms. The CS pressure intensity for the adaptive paradigm was increasing during the four repeated assessments (P CPM-effect was higher using the fixed condition compared with the adaptive condition (P CPM paradigms using a fixed conditioning stimulus produced an increased CPM-effect compared with adaptive and increasing conditioning intensities.

Targeting the Redox Balance in Inflammatory Skin Conditions

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Ditte M. S. Lundvig

2013-04-01

Full Text Available Reactive oxygen species (ROS can be both beneficial and deleterious. Under normal physiological conditions, ROS production is tightly regulated, and ROS participate in both pathogen defense and cellular signaling. However, insufficient ROS detoxification or ROS overproduction generates oxidative stress, resulting in cellular damage. Oxidative stress has been linked to various inflammatory diseases. Inflammation is an essential response in the protection against injurious insults and thus important at the onset of wound healing. However, hampered resolution of inflammation can result in a chronic, exaggerated response with additional tissue damage. In the pathogenesis of several inflammatory skin conditions, e.g., sunburn and psoriasis, inflammatory-mediated tissue damage is central. The prolonged release of excess ROS in the skin can aggravate inflammatory injury and promote chronic inflammation. The cellular redox balance is therefore tightly regulated by several (enzymatic antioxidants and pro-oxidants; however, in case of chronic inflammation, the antioxidant system may be depleted, and prolonged oxidative stress occurs. Due to the central role of ROS in inflammatory pathologies, restoring the redox balance forms an innovative therapeutic target in the development of new strategies for treating inflammatory skin conditions. Nevertheless, the clinical use of antioxidant-related therapies is still in its infancy.

Pain in fibromyalgia and related conditions

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G. Cassisi

2014-06-01

Full Text Available Pain is the hallmark symptom of fibromyalgia (FM and other related syndromes, but quite different from that of other rheumatic diseases, which depends on the degree of damage or inflammation in peripheral tissues. Sufferers are often defined as patients with chronic pain without an underlying mechanistic cause, and these syndromes and their symptoms are most appropriately described as “central pain”, “neuropathic pain”, “nonnociceptive pain” or “central sensitivity syndromes”. The pain is particular, regional or widespread, and mainly relates to the musculoskeletal system; hyperalgesia or allodynia are typical. Its origin is currently considered to be distorted pain or sensory processing, rather than a local or regional abnormality. FM is probably the most important and extensively described central pain syndrome, but the characteristics and features of FM-related pain are similar in other disorders of particular interest for rheumatologists, such as myofascial pain syndromes and temporo-mandibular joint disorders, and there is also an intriguing overlap between FM and benign joint hypermobility syndrome. This suggests that the distinctive aspects of pain in these idiopathic or functional conditions is caused by central nervous system hypersensitivity and abnormalities. Pharmacological and non-pharmacological therapies have been suggested for the treatment of these conditions, but a multidisciplinary approach is required in order to reduce the abnormal cycle of pain amplification and the related maladaptive and self-limiting behaviours.

Nutmeg oil alleviates chronic inflammatory pain through inhibition of COX-2 expression and substance P release in vivo

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Wei Kevin Zhang

2016-04-01

Full Text Available Background: Chronic pain, or sometimes referred to as persistent pain, reduces the life quality of patients who are suffering from chronic diseases such as inflammatory diseases, cancer and diabetes. Hence, herbal medicines draw many attentions and have been shown effective in the treatment or relief of pain. Methods and Results: Here in this study, we used the CFA-injected rats as a sustainable pain model to test the anti-inflammatory and analgesic effect of nutmeg oil, a spice flavor additive to beverages and baked goods produced from the seed of Myristica fragrans tree. Conclusions: We have demonstrated that nutmeg oil could potentially alleviate the CFA-injection induced joint swelling, mechanical allodynia and heat hyperanalgesia of rats through inhibition of COX-2 expression and blood substance P level, which made it possible for nutmeg oil to be a potential chronic pain reliever.

Systematic review: interventions for abdominal pain management in inflammatory bowel disease.

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Norton, C; Czuber-Dochan, W; Artom, M; Sweeney, L; Hart, A

2017-07-01

Abdominal pain is frequently reported by people with inflammatory bowel disease (IBD), including in remission. Pain is an under-treated symptom. To systematically review evidence on interventions (excluding disease-modifying interventions) for abdominal pain management in IBD. Databases (MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Cochrane Library) were searched (February 2016). Two researchers independently screened references and extracted data. Fifteen papers were included: 13 intervention studies and two cross-sectional surveys. A variety of psychological, dietary and pharmacological interventions were reported. Four of six studies reported pain reduction with psychological intervention including individualised and group-based relaxation, disease anxiety-related Cognitive Behavioural Therapy and stress management. Both psychologist-led and self-directed stress management in inactive Crohn's disease reduced pain compared with controls (symptom frequency reduction index=-26.7, -11.3 and 17.2 at 6-month follow-up, respectively). Two dietary interventions (alcoholic drinks with high sugar content and fermentable carbohydrate with prebiotic properties) had an effect on abdominal pain. Antibiotics (for patients with bacterial overgrowth) and transdermal nicotine patches reduced abdominal pain. Current and past cannabis users report it relieves pain. One controlled trial of cannabis reduced SF-36 and EQ-5D pain scores (1.84 and 0.7, respectively). These results must be treated with caution: data were derived from predominantly small uncontrolled studies of moderate to low quality. Few interventions have been tested for IBD abdominal pain. The limited evidence suggests that relaxation and changing cognitions are promising, possibly with individualised dietary changes. There is a need to develop interventions for abdominal pain management in IBD. © 2017 John Wiley & Sons Ltd.

Role overload, pain and physical dysfunction in early rheumatoid or undifferentiated inflammatory arthritis in Canada.

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Mustafa, Sally Sabry; Looper, Karl Julian; Zelkowitz, Phyllis; Purden, Margaret; Baron, Murray

2012-05-03

Inflammatory arthritis impairs participation in societal roles. Role overload arises when the demands by a given role set exceed the resources; time and energy, to carry out the required tasks. The present study examines the association between role overload and disease outcomes in early inflammatory arthritis (EIA). Patients (n = 104) of 7.61 months mean duration of inflammatory arthritis completed self-report questionnaires on sociodemographics, disease characteristics and role overload. Pain was assessed using the Short Form McGill Pain Questionnaire (MPQ) and physical functioning was measured with the Medical Outcomes Study Short Form 36 (SF-36) physical functioning score. Role overload was measured by the Role Overload Scale. Patients indicated the number of social roles they occupied from a total of the three typical roles; marital, parental and paid work. Participants' mean age was 56 years and 70.2% were female. Role overload was not correlated to the number of social roles, however, it was positively associated with pain (p = 0.004) and negatively associated with physical functioning (p = 0.001). On multivariate analysis, role overload was negatively associated with physical functioning after controlling for the relevant sociodemographic variables. This study identifies a possible reciprocal relationship between role overload and physical functioning in patients with EIA.

Physical activity, pain responses to heat stimuli, and conditioned pain modulation in postmenopausal women.

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Adrian, Amanda L; O'Connor, Patrick J; Ward-Ritacco, Christie L; Evans, Ellen M

2015-08-01

Postmenopausal women (PMW) are at high risk for disabling pain and physical inactivity. This study sought to enhance the understanding of relationships between physical activity (PA) and pain among PMW using heat pain sensitivity test and conditioned pain modulation test. We hypothesized that, compared with active women, (i) inactive women would report higher pain intensity and pain unpleasantness ratings; (ii) inactive women in disabling pain would report higher pain intensity and pain unpleasantness at high, but not low, stimulus intensities; and (iii) inactive women would have less modulation. Sixty-eight PMW rated the pain intensity and pain unpleasantness of hot stimuli presented to the thenar eminence of the hand. A subset of 31 women rated the pain intensity of a test stimulus (noxious heat) and a conditioning stimulus (cold water) as part of the conditioned pain modulation task. PA was assessed objectively with accelerometry. Mixed-model analysis of variance (2 × 4 × 2; PA × Temperature × Pain Status) showed that inactive women in disabling pain rated pain unpleasantness higher than active women in disabling pain (F3,192 = 3.526, ∂η = 0.052, P = 0.016). Significantly lower pain unpleasantness ratings were found at the highest stimulus intensity (49°C) only for active women in disabling pain compared with inactive women in disabling pain (t11 = 2.523, P = 0.028). The other hypotheses were not supported. PA is associated with a reduced sensitivity to the unpleasantness of painful high-intensity heat stimuli among women in disabling pain.

Impaired behavioural pain responses in hph-1 mice with inherited deficiency in GTP cyclohydrolase 1 in models of inflammatory pain

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Nasser, A.; Bjerrum, Ole Jannik; Heegaard, A.-M.

2013-01-01

following intraplantar injection of CFA, formalin and capsaicin; whereas decreased basal level of GTP-CH1 activity had no influence in naïve hph-1 mice on acute mechanical and heat pain thresholds. Moreover, the hph-1 mice showed no signs of motor impairment or dystonia-like symptoms......Background: GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin (BH4), encoded by the GCH1 gene, has been implicated in the development and maintenance of inflammatory pain in rats. In humans, homozygous carriers of a " pain-protective" (PP) haplotype...... of the GCH1 gene have been identified exhibiting lower pain sensitivity, but only following pain sensitisation. Ex vivo, the PP GCH1 haplotype is associated with decreased induction of GCH1 after stimulation, whereas the baseline BH4 production is not affected. Contrary, loss of function mutations in the GCH...

Downregulation of selective microRNAs in trigeminal ganglion neurons following inflammatory muscle pain

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Wei Dong

2007-06-01

Full Text Available Abstract Active regulation of gene expression in the nervous system plays an important role in the development and/or maintenance of inflammatory pain. MicroRNA (miRNA negatively regulates gene expression via posttranscriptional or transcriptional inhibition of specific genes. To explore the possible involvement of miRNA in gene regulation during inflammatory pain, we injected complete Freund's adjuvant (CFA unilaterally into the rat masseter muscle and quantified changes in neuron-specific mature miRNAs in the trigeminal ganglion (TG. Real-time reverse-transcription polymerase chain reaction revealed significant, but differential, downregulation of mature miR-10a, -29a, -98, -99a, -124a, -134, and -183 in the ipsilateral mandibular division (V3 of the TG within 4 hr after CFA. In contrast, levels of tested miRNAs did not change significantly in the contralateral V3 or the ipsilateral ophthalmic and maxillary divisions of the TG from inflamed rats, nor in the ipsilateral V3 of saline-injected animals. The downregulated miRNAs recovered differentially to a level equal to or higher than that in naive animals. Full recovery time varied with miRNA species but was at least 4 days. Expression and downregulation of some miRNAs were further confirmed by in situ hybridization of TG neurons that innervate the inflamed muscle. Although neurons of all sizes expressed these miRNAs, their signals varied between neurons. Our results indicate that miRNA species specific to neurons are quickly regulated following inflammatory muscle pain.

Effects of neonatal pain, stress and their interrelation on pain sensitivity in later life in male rats.

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Butkevich, Irina P; Mikhailenko, Viktor A; Vershinina, Elena A; Aloisi, Anna Maria

2016-08-31

Neonatal pain and stress induce long-term changes in pain sensitivity. Therefore their interrelation is a topical subject of clinical and basic research. The present study investigated the effects of inflammatory peripheral pain and stress of maternal deprivation (MD)-isolation in 1-2- and 7-8-day-old Wistar rats (P1,2 and P7,8 respectively, ages comparable to preterm and full-term human babies) on basal pain and pain sensitivity in conditions of inflammatory pain (formalin test) during adolescence. The neonatal impacts were: pain (formalin injection, FOR in the paw), stress (a short 60-min MD), or pain+stress combination (FOR+MD), and appropriate controls. We found that stress of short-term maternal deprivation-isolation and inflammatory pain on P1,2 and P7,8 significantly increased the vulnerability of the nociceptive system to inflammatory pain. Maternal deprivation-isolation on P1,2 as compared with a similar impact on P7,8 had a greater effect on pain sensitivity of the adolescent rats, but the influence of early pain was independent of the injury age. Only adolescent rats with an early combination of pain and maternal deprivation-isolation showed hypoalgesia in the hot plate (HP) test. However licking duration (reflecting pain sensitivity) in these rats did not exceed licking duration in animals exposed only to maternal deprivation-isolation or pain. This study adds new data to the growing body of work demonstrating that early noxious impacts have long-term consequences for the functional activity of the nociceptive system. Our new findings may help to understand the impact of pain and maternal separation in the neonatal intensive care unit.

The ACTTION-American Pain Society Pain Taxonomy (AAPT): an evidence-based and multidimensional approach to classifying chronic pain conditions.

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Fillingim, Roger B; Bruehl, Stephen; Dworkin, Robert H; Dworkin, Samuel F; Loeser, John D; Turk, Dennis C; Widerstrom-Noga, Eva; Arnold, Lesley; Bennett, Robert; Edwards, Robert R; Freeman, Roy; Gewandter, Jennifer; Hertz, Sharon; Hochberg, Marc; Krane, Elliot; Mantyh, Patrick W; Markman, John; Neogi, Tuhina; Ohrbach, Richard; Paice, Judith A; Porreca, Frank; Rappaport, Bob A; Smith, Shannon M; Smith, Thomas J; Sullivan, Mark D; Verne, G Nicholas; Wasan, Ajay D; Wesselmann, Ursula

2014-03-01

Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment. The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial

Effects of low energy shock wave therapy on inflammatory moleculars, bladder pain, and bladder function in a rat cystitis model.

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Wang, Hung-Jen; Lee, Wei-Chia; Tyagi, Pradeep; Huang, Chao-Cheng; Chuang, Yao-Chi

2017-08-01

Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model. Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm 2 ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting. CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812). CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity. © 2016 Wiley Periodicals, Inc.

Psychological factors in oral mucosal and orofacial pain conditions.

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Alrashdan, Mohammad S; Alkhader, Mustafa

2017-01-01

The psychological aspects of chronic pain conditions represent a key component of the pain experience, and orofacial pain conditions are not an exception. In this review, we highlight how psychological factors affect some common oral mucosal and orofacial pain conditions (namely, oral lichen planus, recurrent aphthous stomatitis, burning mouth syndrome, and temporomandibular disorders) with emphasis on the significance of supplementing classical biomedical treatment modalities with appropriate psychological counseling to improve treatment outcomes in targeted patients. A literature search restricted to reports with highest relevance to the selected mucosal and orofacial pain conditions was carried out to retrieve data.

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

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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...

Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain

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Yu Liu

2014-08-01

Full Text Available μ-TRTX-Hhn1b (HNTX-IV is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain. The goal of the present study is to elucidate the analgesic effects of synthetic μ-TRTX-Hhn1b on animal models of pain. The peptide was first synthesized and then successfully refolded/oxidized. The synthetic peptide had the same inhibitory effect on human Nav1.7 current transiently expressed in HEK 293 cells as the native toxin. Furthermore, the analgesic potentials of the synthetic peptide were examined on models of inflammatory pain and neuropathic pain. μ-TRTX-Hhn1b produced an efficient reversal of acute nociceptive pain in the abdominal constriction model, and significantly reduced the pain scores over the 40-min period in the formalin model. The efficiency of μ-TRTX-Hhn1b on both models was equivalent to that of morphine. In the spinal nerve model, the reversal effect of μ-TRTX-Hhn1b on allodynia was longer and higher than mexiletine. These results demonstrated that μ-TRTX-Hhn1b efficiently alleviated acute inflammatory pain and chronic neuropathic pain in animals and provided an attractive template for further clinical analgesic drug design.

The ACTTION–APS–AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions

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Kent, Michael L.; Tighe, Patrick J.; Belfer, Inna; Brennan, Timothy J.; Bruehl, Stephen; Brummett, Chad M.; Buckenmaier, Chester C.; Buvanendran, Asokumar; Cohen, Robert I.; Desjardins, Paul; Edwards, David; Fillingim, Roger; Gewandter, Jennifer; Gordon, Debra B.; Hurley, Robert W.; Kehlet, Henrik; Loeser, John D.; Mackey, Sean; McLean, Samuel A.; Polomano, Rosemary; Rahman, Siamak; Raja, Srinivasa; Rowbotham, Michael; Suresh, Santhanam; Schachtel, Bernard; Schreiber, Kristin; Schumacher, Mark; Stacey, Brett; Stanos, Steven; Todd, Knox; Turk, Dennis C.; Weisman, Steven J.; Wu, Christopher; Carr, Daniel B.; Dworkin, Robert H.; Terman, Gregory

2017-01-01

Objective. With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting. Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods. As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective. The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions. Significant numbers of patients still suffer from significant acute pain

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

Science.gov (United States)

Kent, Michael L; Tighe, Patrick J; Belfer, Inna; Brennan, Timothy J; Bruehl, Stephen; Brummett, Chad M; Buckenmaier, Chester C; Buvanendran, Asokumar; Cohen, Robert I; Desjardins, Paul; Edwards, David; Fillingim, Roger; Gewandter, Jennifer; Gordon, Debra B; Hurley, Robert W; Kehlet, Henrik; Loeser, John D; Mackey, Sean; McLean, Samuel A; Polomano, Rosemary; Rahman, Siamak; Raja, Srinivasa; Rowbotham, Michael; Suresh, Santhanam; Schachtel, Bernard; Schreiber, Kristin; Schumacher, Mark; Stacey, Brett; Stanos, Steven; Todd, Knox; Turk, Dennis C; Weisman, Steven J; Wu, Christopher; Carr, Daniel B; Dworkin, Robert H; Terman, Gregory

2017-05-01

With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies

Pain adaptability in individuals with chronic musculoskeletal pain is not associated with conditioned pain modulation

DEFF Research Database (Denmark)

Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun

2018-01-01

(MSK). CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic non-specific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability...... at both CPTs were highly correlated. PA and PNA did not differ in their demographics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t41=-2.76, p... days whereas PNA did not (F (6,246) = 3.01, p = 0.01). The dichotomy of pain adaptability exists in MSK patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition which...

Dissociable Learning Processes Underlie Human Pain Conditioning.

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Zhang, Suyi; Mano, Hiroaki; Ganesh, Gowrishankar; Robbins, Trevor; Seymour, Ben

2016-01-11

Pavlovian conditioning underlies many aspects of pain behavior, including fear and threat detection [1], escape and avoidance learning [2], and endogenous analgesia [3]. Although a central role for the amygdala is well established [4], both human and animal studies implicate other brain regions in learning, notably ventral striatum and cerebellum [5]. It remains unclear whether these regions make different contributions to a single aversive learning process or represent independent learning mechanisms that interact to generate the expression of pain-related behavior. We designed a human parallel aversive conditioning paradigm in which different Pavlovian visual cues probabilistically predicted thermal pain primarily to either the left or right arm and studied the acquisition of conditioned Pavlovian responses using combined physiological recordings and fMRI. Using computational modeling based on reinforcement learning theory, we found that conditioning involves two distinct types of learning process. First, a non-specific "preparatory" system learns aversive facial expressions and autonomic responses such as skin conductance. The associated learning signals-the learned associability and prediction error-were correlated with fMRI brain responses in amygdala-striatal regions, corresponding to the classic aversive (fear) learning circuit. Second, a specific lateralized system learns "consummatory" limb-withdrawal responses, detectable with electromyography of the arm to which pain is predicted. Its related learned associability was correlated with responses in ipsilateral cerebellar cortex, suggesting a novel computational role for the cerebellum in pain. In conclusion, our results show that the overall phenotype of conditioned pain behavior depends on two dissociable reinforcement learning circuits. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

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Liao, Hsien-Yin; Hsieh, Ching-Liang; Huang, Chun-Ping; Lin, Yi-Wen

2017-02-13

Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N 6 -cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.

Medication overuse reinstates conditioned pain modulation in women with migraine.

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Guy, Nathalie; Voisin, Daniel; Mulliez, Aurélien; Clavelou, Pierre; Dallel, Radhouane

2018-05-01

Background This study investigated the effects of medication overuse and withdrawal on modulation of pain processing in women with migraine. Temporal summation of laser-evoked thermal pain was used to measure the effects of conditioned pain modulation. Methods 36 female participants (12 healthy volunteers, 12 with episodic migraine and 12 with medication overuse headache) were included in a two session protocol. Medication overuse headache subjects were also tested three weeks after medication overuse headache withdrawal. Mechanical and laser-evoked thermal pain thresholds were measured on the back of the non-dominant hand where, later, temporal summation of laser-evoked thermal pain to repetitive thermal stimuli was elicited for 30 min, at an intensity producing moderate pain. Between the 10 th and 20 th minutes, the contralateral foot was immersed into a water bath at a not painful (30℃) or painfully cold (8℃; conditioned pain modulation) temperature. Results Episodic migraine, medication overuse headache and medication overuse headache withdrawal were associated with an increase in extracephalic temporal summation of laser-evoked thermal pain as compared to healthy volunteer subjects, while there was no alteration of laser-evoked thermal and mechanical extracephalic pain thresholds in these subjects. Conditioned pain modulation was highly efficient in temporal summation of laser-evoked thermal pain in healthy volunteer subjects, with a solid post-effect (reduction of pain). Conditioned pain modulation was still present, but reduced, in episodic migraine. By contrast, conditioned pain modulation was normal in medication overuse headache and strongly reduced in medication overuse headache withdrawal. Furthermore, in medication overuse headache withdrawal, the post-effect was no longer a decrease, but a facilitation of pain. Conclusions These data show that a decrease in conditioned pain modulation does not underlie medication overuse headache in women. On

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

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Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Deficient conditioned pain modulation after spinal cord injury correlates with clinical spontaneous pain measures.

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Albu, Sergiu; Gómez-Soriano, Julio; Avila-Martin, Gerardo; Taylor, Julian

2015-02-01

The contribution of endogenous pain modulation dysfunction to clinical and sensory measures of neuropathic pain (NP) has not been fully explored. Habituation, temporal summation, and heterotopic noxious conditioning stimulus-induced modulation of tonic heat pain intensity were examined in healthy noninjured subjects (n = 10), and above the level of spinal cord injury (SCI) in individuals without (SCI-noNP, n = 10) and with NP (SCI-NP, n = 10). Thermoalgesic thresholds, Cz/AFz contact heat evoked potentials (CHEPs), and phasic or tonic (30 seconds) heat pain intensity were assessed within the C6 dermatome. Although habituation to tonic heat pain intensity (0-10) was reported by the noninjured (10 s: 3.5 ± 0.3 vs 30 s: 2.2 ± 0.5 numerical rating scale; P = 0.003), loss of habituation was identified in both the SCI-noNP (3.8 ± 0.3 vs 3.6 ± 0.5) and SCI-NP group (4.2 ± 0.4 vs 4.9 ± 0.8). Significant temporal summation of tonic heat pain intensity was not observed in the 3 groups. Inhibition of tonic heat pain intensity induced by heterotopic noxious conditioning stimulus was identified in the noninjured (-29.7% ± 9.7%) and SCI-noNP groups (-19.6% ± 7.0%), but not in subjects with SCI-NP (+1.1% ± 8.0%; P pain modulation response correlated positively with Cz/AFz CHEP amplitude (ρ = 0.8; P = 0.015) and evoked heat pain intensity (ρ = 0.8; P = 0.007) in the SCI-NP group. Stepwise regression analysis revealed that the mean conditioned pain modulation (R = 0.72) correlated with pain severity and pressing spontaneous pain in the SCI-NP group. Comprehensive assessment of sensory dysfunction above the level of injury with tonic thermal test and conditioning stimuli revealed less-efficient endogenous pain modulation in subjects with SCI-NP.

Conditioned pain modulation: a predictor for development and treatment of neuropathic pain.

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Granovsky, Yelena

2013-09-01

Psychophysical evaluation of endogenous pain inhibition via conditioned pain modulation (CPM) represents a new generation of laboratory tests for pain assessment. In this review we discuss recent findings on CPM in neuropathic pain and refer to psychophysical, neurophysiological, and methodological aspects of its clinical implications. Typically, chronic neuropathic pain patients express less efficient CPM, to the extent that incidence of acquiring neuropathic pain (e.g. post-surgery) and its intensity can be predicted by a pre-surgery CPM assessment. Moreover, pre-treatment CPM evaluation may assist in the correct choice of serotonin-noradrenalin reuptake inhibitor analgesic agents for individual patients. Evaluation of pain modulation capabilities can serve as a step forward in individualizing pain medicine.

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.

Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

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Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

2015-07-01

Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pain from Dental Implant Placement, Inflammatory Pulpitis Pain, and Neuropathic Pain Present Different Somatosensory Profiles.

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Porporatti, André Luís; Bonjardim, Leonardo Rigoldi; Stuginski-Barbosa, Juliana; Bonfante, Estevam Augusto; Costa, Yuri Martins; Rodrigues Conti, Paulo César

2017-01-01

To address the two following questions: (1) What kind of somatosensory abnormalities may be characterized in patients receiving dental implants (IMP), in ongoing inflammatory dental pulpitis (IP) patients, and in neuropathic pain (atypical odontalgia [AO]) patients? and (2) What sort of sensory and neural changes may result from dental implant placement surgery and pulpectomy? A total of 60 subjects were divided into three groups: the IMP (n = 20), IP (n = 20), and AO groups (n = 20). Quantitative sensory testing (QST) was performed preoperatively (baseline) for all three groups and postoperatively at 1 month and 3 months after dental implant placement or pulpectomy (in the IMP group and IP group, respectively). Statistical analyses were completed with one-way and two-way analysis of variance and z score transformations (α = 5%). The main findings of this study indicated that: (1) Elevations in mechanical detection threshold (MDT) and in current perception threshold (CPT) related to C-fiber activation, indicating a loss of function, were found at baseline in IP patients; (2) Somatosensory abnormalities such as allodynia, reduced MDT and mechanical pain threshold (MPT), and impaired pain modulation were found in AO patients; (3) No somatosensory alterations after implant placement were found in the IMP group; and (4) Somatosensory alterations in the form of reduction in the CPT related to C-fiber activation were reported 3 months after pulpectomy in the IP group. This study showed that somatosensory abnormalities were evident in AO and IP patients, and somatosensory alterations were seen in IP patients even 3 months after pulpectomy. However, no somatosensory alterations were seen after implant placement.

Chronic widespread pain in spondyloarthritis

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F. Atzeni

2014-06-01

Full Text Available The pain associated with spondyloarthritis (SpA can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP that characterises fibromyalgia (FM. The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification.

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Maixner, William; Fillingim, Roger B; Williams, David A; Smith, Shad B; Slade, Gary D

2016-09-01

There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs. This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36–ST37 Acupoints on CFA-induced Inflammatory Pain

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Lu, Kung-Wen; Hsu, Chao-Kuei; Hsieh, Ching-Liang; Yang, Jun; Lin, Yi-Wen

2016-01-01

Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund’s adjuvant (CFA), (2.14 ± 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain. PMID:26906464

Radiation treatment of painful degenerative skeletal conditions

International Nuclear Information System (INIS)

Schaefer, U.; Micke, O.; Willich, N.

1996-01-01

The study reported was intended to present own experience with irradiation for treatment of painful degenerative skeletal conditions and examine the long-term effects of this treatment. A retrospective study was performed covering the period from 1985 until 1991, examining 157 patients suffering from painful degenerative skeletal conditions who entered information on the success of their radiation treatment in a questionnaire. 94 of the questionnaires could be used for evaluation. Pain anamnesis revealed periods of more than one year in 45% of the cases. 74% of the patients had been treated without success with drug or orthopedic therapy. Immediately after termination of the radiotherapy, 38% of the patients said to be free of pain or to feel essentially relieved, while at the time the questionnaire was distributed, the percentage was 76%. Thus in our patient material, radiotherapy for treatment of painful degenerative skeletal lesions was successful in 76% of the cases and for long post-treatment periods, including those cases whith long pain anamnesis and unsuccessful conventional pre-treatment. (orig./MG) [de

Modulation of Itch by Conditioning Itch and Pain Stimulation in Healthy Humans.

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Andersen, Hjalte H; van Laarhoven, Antoinette I M; Elberling, Jesper; Arendt-Nielsen, Lars

2017-12-01

Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation. There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch and pain. This study aimed to investigate whether and the extent to which itch can be modulated by conditioning itch and pain stimuli. Twenty-six healthy volunteers participated. The study consisted of 5 conditions designed to systematically assess endogenous modulation of itch or pain: 1) itch-induced modulation of contralateral itch, 2) pain-induced modulation of contralateral itch, 3) pain-induced modulation of ipsilateral itch, 4) pain-induced modulation of contralateral pain, and 5) itch-induced modulation of contralateral pain. Conditioning stimuli were cold pressor-induced pain and histamine-evoked itch, whereas the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (conditioned pain modulation-effect) by the conditioning pain stimulus (P modulation-effect) by contra- as well as ipsilateral applied conditioning pain (both P modulation of itch as well as pain in humans. Future studies addressing potential aberrations in pain-evoked descending modulation of itch in chronic itch patients are warranted. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

OpenAIRE

Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

2013-01-01

GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently inc...

Risk for haematological malignancies after radiation treatment of painful benign conditions in the skeleton

International Nuclear Information System (INIS)

Johansson, L.; Larsson, L.G.; Damber, L.

1999-01-01

X-ray therapy of painful and inflammatory changes in joints and adjacent structures was very common in Sweden during the period from 1940 until the beginning of the 1960:s. These patients comprise a comprehensive material pertinent for epidemiological studies. The present study deals with a cohort of c. 27,400 patients from 3 hospitals in northern Sweden, who 1950 - 1964 received x-ray treatment for benign painful conditions. The distribution of the absorbed dose in the red marrow was estimated. The average mean absorbed dose in red bone marrow was 0.4 Gy for the total cohort. The number of leukaemia cases observed in the cohort was obtained from the Swedish Cancer Register for the period 1958 - 1995. The study indicates a slightly increased leukaemia risk with borderline statistical significance in the highest dose group. (au)

Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

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Eccleston, Christopher; Cooper, Tess E; Fisher, Emma; Anderson, Brian; Wilkinson, Nick Mr

2017-08-02

Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. We searched the Cochrane

Evaluation of clinical and inflammatory profile in opioid addiction patients with comorbid pain: results from a multicenter investigation

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Dennis BB

2014-11-01

Full Text Available Brittany B Dennis,1 M Constantine Samaan,2 Monica Bawor,3 James Paul,4 Carolyn Plater,5 Guillaume Pare,1 Andrew Worster,6 Michael Varenbut,5 Jeff Daiter,5 David C Marsh,5,7 Dipika Desai,8 Lehana Thabane,1,9,10 Zainab Samaan1,8,11 1Department of Clinical Epidemiology and Biostatistics, 2Department of Pediatrics, Division of Pediatric Endocrinology, 3McMaster Integrative Neuroscience Discovery and Study Program, 4Department of Anesthesia, McMaster University, Hamilton, 5Ontario Addiction Treatment Centres, Richmond Hill, 6Department of Medicine, Hamilton General Hospital, Hamilton, 7Northern Ontario School of Medicine, Sudbury, 8Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, 9Centre for Evaluation of Medicine, 10System Linked Research Unit, Hamilton, 11Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT, with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population.Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235 on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and

Contemporary views on inflammatory pain mechanisms: TRPing over innate and microglial pathways [version 1; referees: 3 approved

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Zhonghui Guan

2016-09-01

Full Text Available Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death. The complexity of the inflammatory response reflects not only the inciting event (infection, trauma, surgery, cancer, or autoimmune but also the involvement of heterogeneous cell types including neuronal (primary afferents, sensory ganglion, and spinal cord, non-neuronal (endothelial, keratinocytes, epithelial, and fibroblasts, and immune cells. In this commentary, we will examine 1. the expression and regulation of two members of the transient receptor potential family in primary afferent nociceptors and their activation/regulation by products of inflammation, 2. the role of innate immune pathways that drive inflammation, and 3. the central nervous system’s response to injury with a focus on the activation of spinal microglia driving painful hyperalgesic states.

Pain Adaptability in Individuals With Chronic Musculoskeletal Pain Is Not Associated With Conditioned Pain Modulation.

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Wan, Dawn Wong Lit; Arendt-Nielsen, Lars; Wang, Kelun; Xue, Charlie Changli; Wang, Yanyi; Zheng, Zhen

2018-03-27

Healthy humans can be divided into the pain adaptive (PA) and the pain nonadaptive (PNA) groups; PA showed a greater decrease in pain rating to a cold pressor test (CPT) than PNA. This study examined if the dichotomy of pain adaptability existed in individuals with chronic musculoskeletal pain. CPTs at 2°C and 7°C were used to assess the status of pain adaptability in participants with either chronic nonspecific low back pain or knee osteoarthritis. The participants' potency of conditioned pain modulation (CPM) and local inhibition were measured. The strengths of pain adaptability at both CPTs were highly correlated. PA and PNA did not differ in their demographic characteristics, pain thresholds from thermal and pressure stimuli, or potency of local inhibition or CPM. PA reached their maximum pain faster than PNA (t 41 = -2.76, P adaptability exists in musculoskeletal pain patients. Consistent with the healthy human study, the strength of pain adaptability and potency of CPM are not related. Pain adaptability could be another form of endogenous pain inhibition of which clinical implication is yet to be understood. The dichotomy of pain adaptability was identified in healthy humans. The current study confirms that this dichotomy also exists in individuals with chronic musculoskeletal pain, and could be reliably assessed with CPTs at 2°C and 7°C. Similar to the healthy human study, pain adaptability is not associated with CPM, and may reflect the temporal aspect of pain inhibition. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Nociception and role of immune system in pain.

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Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

2015-09-01

Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

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Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

2016-02-01

Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

[Evaluation of anti-inflammatory activity of extracts from Siberian plants].

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Nesterova, Iu V; Povet'eva, T N; Aksinenko, S G; Suslov, N I; Gaĭdamovich, N N; Nagorniak, Iu G; Popova, E V; Kravtsova, S S; Andreeva, T I

2009-01-01

Experimental investigations have shown that water-alcohol extracts from plants containing alkaloids (Aconitum baikalense, Aconitum septentrionale, Delphinium elatum L., Conium maculatum) and salicylic acid (Filipendula ulmaria, Salix viminalis, Fragaria vesca, Rubus idaeus) inhibited the development of main symptoms of inflammation, viz. exudation, pain, fever, to the same extent as non-steroidal anti-inflammatory agents. The substances studied in this work may be used to develop new efficient pharmacological preparations for the treatment of different inflammatory conditions associated with severe pain syndrome.

Operant conditioning of enhanced pain sensitivity by heat-pain titration.

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Becker, Susanne; Kleinböhl, Dieter; Klossika, Iris; Hölzl, Rupert

2008-11-15

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.

Assessment and manifestation of central sensitisation across different chronic pain conditions.

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Arendt-Nielsen, L; Morlion, B; Perrot, S; Dahan, A; Dickenson, A; Kress, H G; Wells, C; Bouhassira, D; Mohr Drewes, A

2018-02-01

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based

Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

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Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

2008-01-01

Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

Fatigue, Pain, Anxiety and Depression in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

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Merkies, Ingemar S J; Kieseier, Bernd C

2016-01-01

In the clinical evaluation of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), scant attention is paid to symptoms such as fatigue, pain and anxiety/depression. We aimed at addressing seminal studies that focused on the burden of these symptoms and their impact on quality of life (QoL) in these conditions. Fatigue, pain, and anxiety/depression are increasingly being recognized in patients with GBS and CIDP, although their pathophysiological provenance remains unknown. Fatigue and pain are significant in terms of prevalence and intensity, may be a presenting symptom, and can persist for years after apparent functional recovery, suggesting residual injury. Anxiety/depression has also been examined although studies are limited. Despite their negative impact on QoL, the long-term dynamics of these symptoms in patients with GBS and particularly CIDP receiving therapy in routine clinical practice have not been systematically evaluated. Such observations formed the basis for the ongoing (GAMEDIS) studies evaluating the effect of Gamunex on fatigue and depression in patients with CIDP, of which some preliminary data are presented. Strength and sensory deficits are the main areas of focus in patients with GBS and CIDP, but they do not explain the total reduction in QoL, suggesting the possible role of other complaints. A more comprehensive approach to patient care demands that factors such as pain, fatigue and anxiety/depression receive greater attention. The non-interventional GAMEDIS studies are expected to provide valuable insight into the long-term effectiveness of Gamunex in everyday practice. © 2016 S. Karger AG, Basel.

Lack of effect of chronic pre-treatment with the FAAH inhibitor URB597 on inflammatory pain behaviour: evidence for plastic changes in the endocannabinoid system

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Okine, Bright N; Norris, Leonie M; Woodhams, Stephen; Burston, James; Patel, Annie; Alexander, Stephen PH; Barrett, David A; Kendall, David A; Bennett, Andrew J; Chapman, Victoria

2012-01-01

BACKGROUND AND PURPOSE Elevating levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is a major focus of pain research, purported to be a safer approach devoid of cannabinoid receptor-mediated side effects. Here, we have determined the effects of sustained pharmacological inhibition of FAAH on inflammatory pain behaviour and if pharmacological inhibition of FAAH was as effective as genetic deletion of FAAH on pain behaviour. EXPERIMENTAL APPROACH Effects of pre-treatment with a single dose, versus 4 day repeated dosing with the selective FAAH inhibitor, URB597 (i.p. 0.3 mg·kg−1), on carrageenan-induced inflammatory pain behaviour and spinal pro-inflammatory gene induction were determined in rats. Effects of pain induction and of the drug treatments on levels of arachidonoyl ethanolamide (AEA), palmitoyl ethanolamide (PEA) and oleolyl ethanolamide (OEA) in the spinal cord were determined. KEY RESULTS Single, but not repeated, URB597 treatment significantly attenuated the development of inflammatory hyperalgesia (P < 0.001, vs. vehicle-treated animals). Neither mode of URB597 treatment altered levels of AEA, PEA and OEA in the hind paw, or carrageenan-induced paw oedema. Single URB597 treatment produced larger increases in AEA, PEA and OEA in the spinal cord, compared with those after repeated administration. Single and repeated URB597 treatment decreased levels of immunoreactive N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) in the spinal cord and attenuated carrageenan-induced spinal pro-inflammatory gene induction. CONCLUSION AND IMPLICATIONS Changes in the endocannabinoid system may contribute to the loss of analgesic effects following repeated administration of low dose URB597 in this model of inflammatory pain. PMID:22595021

Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

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Yul Huh

2017-08-01

Full Text Available Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain, and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.

Conditioned pain modulation is minimally influenced by cognitive evaluation or imagery of the conditioning stimulus

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Bernaba M

2014-11-01

Full Text Available Mario Bernaba, Kevin A Johnson, Jiang-Ti Kong, Sean MackeyStanford Systems Neuroscience and Pain Laboratory, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: Conditioned pain modulation (CPM is an experimental approach for probing endogenous analgesia by which one painful stimulus (the conditioning stimulus may inhibit the perceived pain of a subsequent stimulus (the test stimulus. Animal studies suggest that CPM is mediated by a spino–bulbo–spinal loop using objective measures such as neuronal firing. In humans, pain ratings are often used as the end point. Because pain self-reports are subject to cognitive influences, we tested whether cognitive factors would impact on CPM results in healthy humans.Methods: We conducted a within-subject, crossover study of healthy adults to determine the extent to which CPM is affected by 1 threatening and reassuring evaluation and 2 imagery alone of a cold conditioning stimulus. We used a heat stimulus individualized to 5/10 on a visual analog scale as the testing stimulus and computed the magnitude of CPM by subtracting the postconditioning rating from the baseline pain rating of the heat stimulus.Results: We found that although evaluation can increase the pain rating of the conditioning stimulus, it did not significantly alter the magnitude of CPM. We also found that imagery of cold pain alone did not result in statistically significant CPM effect.Conclusion: Our results suggest that CPM is primarily dependent on sensory input, and that the cortical processes of evaluation and imagery have little impact on CPM. These findings lend support for CPM as a useful tool for probing endogenous analgesia through subcortical mechanisms.Keywords: conditioned pain modulation, endogenous analgesia, evaluation, imagery, cold presser test, CHEPS, contact heat-evoked potential stimulator

Orofacial neuropathic pain mouse model induced by Trigeminal Inflammatory Compression (TIC of the infraorbital nerve

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Ma Fei

2012-12-01

Full Text Available Abstract Background Trigeminal neuropathic pain attacks can be excruciating for patients, even after being lightly touched. Although there are rodent trigeminal nerve research models to study orofacial pain, few models have been applied to studies in mice. A mouse trigeminal inflammatory compression (TIC model is introduced here which successfully and reliably promotes vibrissal whisker pad hypersensitivity. Results The chronic orofacial neuropathic pain model is induced after surgical placement of chromic gut suture in the infraorbital nerve fissure in the maxillary bone. Slight compression and chemical effects of the chromic gut suture on the portion of the infraorbital nerve contacted cause mild nerve trauma. Nerve edema is observed in the contacting infraorbital nerve bundle as well as macrophage infiltration in the trigeminal ganglia. Centrally in the spinal trigeminal nucleus, increased immunoreactivity for an activated microglial marker is evident (OX42, postoperative day 70. Mechanical thresholds of the affected whisker pad are significantly decreased on day 3 after chromic gut suture placement, persisting at least 10 weeks. The mechanical allodynia is reversed by suppression of microglial activation. Cold allodynia was detected at 4 weeks. Conclusions A simple, effective, and reproducible chronic mouse model mimicking clinical orofacial neuropathic pain (Type 2 is induced by placing chromic gut suture between the infraorbital nerve and the maxillary bone. The method produces mild inflammatory compression with significant continuous mechanical allodynia persisting at least 10 weeks and cold allodynia measureable at 4 weeks.

Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.

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Yarnitsky, David; Granot, Michal; Nahman-Averbuch, Hadas; Khamaisi, Mogher; Granovsky, Yelena

2012-06-01

This study aims to individualize the selection of drugs for neuropathic pain by examining the potential coupling of a given drug's mechanism of action with the patient's pain modulation pattern. The latter is assessed by the conditioned pain modulation (CPM) and temporal summation (TS) protocols. We hypothesized that patients with a malfunctioning pain modulation pattern, such as less efficient CPM, would benefit more from drugs augmenting descending inhibitory pain control than would patients with a normal modulation pattern of efficient CPM. Thirty patients with painful diabetic neuropathy received 1 week of placebo, 1 week of 30 mg/d duloxetine, and 4 weeks of 60 mg/d duloxetine. Pain modulation was assessed psychophysically, both before and at the end of treatment. Patient assessment of drug efficacy, assessed weekly, was the study's primary outcome. Baseline CPM was found to be correlated with duloxetine efficacy (r=0.628, P<.001, efficient CPM is marked negative), such that less efficient CPM predicted efficacious use of duloxetine. Regression analysis (R(2)=0.673; P=.012) showed that drug efficacy was predicted only by CPM (P=.001) and not by pretreatment pain levels, neuropathy severity, depression level, or patient assessment of improvement by placebo. Furthermore, beyond its predictive value, the treatment-induced improvement in CPM was correlated with drug efficacy (r=-0.411, P=.033). However, this improvement occurred only in patients with less efficient CPM (16.8±16.0 to -1.1±15.5, P<.050). No predictive role was found for TS. In conclusion, the coupling of CPM and duloxetine efficacy highlights the importance of pain pathophysiology in the clinical decision-making process. This evaluative approach promotes personalized pain therapy. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.

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Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars

2014-05-01

This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The roles of special proresolving mediators in pain relief.

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Zhang, Lan-Yu; Jia, Ming-Rui; Sun, Tao

2018-02-08

The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders. Due to the potent proresolving and anti-inflammatory effects, SPMs are also used for pain relief. This review focuses on the mechanisms by which SPMs act on their respective G-protein-coupled receptors in immune cells and nerve cells to normalize pain via regulating inflammatory mediators, transient receptor potential ion channels, and central sensitization. SPMs may offer novel therapeutic approaches for preventing and treating pain conditions associated with inflammation.

Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

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Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

2015-06-04

Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-Term Effects of Neonatal Pain and Stress on Reactivity of the Nociceptive System.

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Butkevich, I P; Mikhailenko, V A

2016-10-01

The influence of inflammatory pain and/or weaning stress at different terms of neonatal development on functional activity of the nociceptive system during adulthood was studied in rats. Repeated stress in 1-2-day-old rat pups (a premature baby model) enhanced pain sensitivity to peripheral inflammation in both males and females. Repeated inflammatory pain experienced by male pups aged 1-2 or 7-8 days (models of preterm and full-term baby), even in presence of mother, enhanced pain behavior under conditions of repeated inflammatory pain in adulthood. Pain sensitivity in adult animals before (hot plate test) and after formation of the inflammatory focus (formalin test) depended on the age when the animals were subjected to the injury, type of exposure, and on animal sex. The priority data obtained by us will help to understand the mechanisms of long-term effects of early injuries and are important for pediatricians and neonatologists.

Current advances in orthodontic pain

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Long, Hu; Wang, Yan; Jian, Fan; Liao, Li-Na; Yang, Xin; Lai, Wen-Li

2016-01-01

Orthodontic pain is an inflammatory pain that is initiated by orthodontic force-induced vascular occlusion followed by a cascade of inflammatory responses, including vascular changes, the recruitment of inflammatory and immune cells, and the release of neurogenic and pro-inflammatory mediators. Ultimately, endogenous analgesic mechanisms check the inflammatory response and the sensation of pain subsides. The orthodontic pain signal, once received by periodontal sensory endings, reaches the sensory cortex for pain perception through three-order neurons: the trigeminal neuron at the trigeminal ganglia, the trigeminal nucleus caudalis at the medulla oblongata and the ventroposterior nucleus at the thalamus. Many brain areas participate in the emotion, cognition and memory of orthodontic pain, including the insular cortex, amygdala, hippocampus, locus coeruleus and hypothalamus. A built-in analgesic neural pathway—periaqueductal grey and dorsal raphe—has an important role in alleviating orthodontic pain. Currently, several treatment modalities have been applied for the relief of orthodontic pain, including pharmacological, mechanical and behavioural approaches and low-level laser therapy. The effectiveness of nonsteroidal anti-inflammatory drugs for pain relief has been validated, but its effects on tooth movement are controversial. However, more studies are needed to verify the effectiveness of other modalities. Furthermore, gene therapy is a novel, viable and promising modality for alleviating orthodontic pain in the future. PMID:27341389

p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats.

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Kiyomoto, Masaaki; Shinoda, Masamichi; Honda, Kuniya; Nakaya, Yuka; Dezawa, Ko; Katagiri, Ayano; Kamakura, Satoshi; Inoue, Tomio; Iwata, Koichi

2015-08-12

Orofacial inflammatory pain is likely to accompany referred pain in uninflamed orofacial structures. The ectopic pain precludes precise diagnosis and makes treatment problematic, because the underlying mechanism is not well understood. Using the established ectopic orofacial pain model induced by complete Freund's adjuvant (CFA) injection into trapezius muscle, we analyzed the possible role of p38 phosphorylation in activated microglia in ectopic orofacial pain. Mechanical allodynia in the lateral facial skin was induced following trapezius muscle inflammation, which accompanied microglial activation with p38 phosphorylation and hyperexcitability of wide dynamic range (WDR) neurons in the trigeminal spinal subnucleus caudalis (Vc). Intra-cisterna successive administration of a p38 mitogen-activated protein kinase selective inhibitor, SB203580, suppressed microglial activation and its phosphorylation of p38. Moreover, SB203580 administration completely suppressed mechanical allodynia in the lateral facial skin and enhanced WDR neuronal excitability in Vc. Microglial interleukin-1β over-expression in Vc was induced by trapezius muscle inflammation, which was significantly suppressed by SB203580 administration. These findings indicate that microglia, activated via p38 phosphorylation, play a pivotal role in WDR neuronal hyperexcitability, which accounts for the mechanical hypersensitivity in the lateral facial skin associated with trapezius muscle inflammation.

Acute dental pain II

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Jonasson, Peter; Kirkevang, Lise-Lotte; Rosen, Annika

2016-01-01

Acute dental pain most often occurs in relation to inflammatory conditions in the dental pulp or in the periradicular tissues surrounding a tooth, but it is not always easy to reach a diagnose and determine what treatment to perform. The anamnesis and the clinical examination provide valuable...

The application of conditioning paradigms in the measurement of pain.

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Li, Jun-Xu

2013-09-15

Pain is a private experience that involves both sensory and emotional components. Animal studies of pain can only be inferred by their responses, and therefore the measurement of reflexive responses dominates the pain literature for nearly a century. It has been argued that although reflexive responses are important to unveil the sensory nature of pain in organisms, pain affect is equally important but largely ignored in pain studies primarily due to the lack of validated animal models. One strategy to begin to understand pain affect is to use conditioning principles to indirectly reveal the affective condition of pain. This review critically analyzed several procedures that are thought to measure affective learning of pain. The procedures regarding the current knowledge, the applications, and their advantages and disadvantages in pain research are discussed. It is proposed that these procedures should be combined with traditional reflex-based pain measurements in future studies of pain, which could greatly benefit both the understanding of neural underpinnings of pain and preclinical assessment of novel analgesics. © 2013 Elsevier B.V. All rights reserved.

Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish General Population: The DanFunD Study

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Skovbjerg, Sine; Jørgensen, Torben; Arendt-Nielsen, Lars

2017-01-01

with cold pressor pain (hand) for 2 minutes. Conditioning pain intensity was assessed using a visual analog scale and questionnaire data were collected. Female sex (P stress......Increased pressure pain sensitivity and impaired descending pain control have been associated with chronic pain, but knowledge on the variability in the adult general population is lacking. Pressure pain thresholds (PPTs) and descending pain control assessed using conditioned pain modulation (CPM...... (P ≤ .02), and high visual analog scale score (P ≤ .02) were associated with a larger CPM response. PERSPECTIVE: Data from this large population-based study provide new insight into the gender and age variation in pain sensitivity and CPM response. Decreased CPM potency and increased pain sensitivity...

Learned helplessness predicts functional disability, pain and fatigue in patients with recent-onset inflammatory polyarthritis.

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Camacho, Elizabeth M; Verstappen, Suzanne M M; Chipping, Jacqueline; Symmons, Deborah P M

2013-07-01

Cross-sectional studies have found that learned helplessness (LH) is associated with disease outcome in patients with RA. However, little is known about the longitudinal impact of LH. The aim of this study was to investigate whether LH is associated with future disease outcome (disability, pain and fatigue) and to investigate whether LH changes over time in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Patients included in this investigation had been recruited to the Norfolk Arthritis Register, a primary-care-based inception cohort. LH was measured at baseline as patients' total score on the Rheumatology Attitudes Index (RAI). A total of 443 patients completed the HAQ and visual analogue scales of pain and fatigue at baseline and after 2 years of follow-up. Greater feelings of LH at baseline were associated with higher HAQ scores at follow-up [difference in HAQ score per 1-point increase in RAI score (β-coefficient) 0.02; 95% CI 0.01, 0.04]. Greater baseline LH was also associated with more pain (β-coefficient 1.0; 95% CI 0.4, 1.5) and more fatigue (β-coefficient 1.0; 95% CI 0.2, 1.4) at follow-up. LH was highly changeable during follow-up, with 87% of patients showing any change and 50% improving. Baseline LH independently predicted disability, pain and fatigue at follow-up. Half of patients reported fewer feelings of helplessness after 2 years of follow-up, suggesting that LH may potentially be a modifiable risk factor for disease outcome in IP and a target for intervention.

Attitudes of farmers and veterinarians towards pain and the use of pain relief in pigs.

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Ison, S H; Rutherford, K M D

2014-12-01

A survey of UK-based pig farmers and veterinarians was conducted, in order to investigate attitudes to pain and the use of pain relief in pigs. Survey respondents were asked to indicate which anti-inflammatory drugs they used or prescribed for pigs, how often these were administered, and the level of pain they associated with particular conditions. The survey found that veterinarians used a range of anti-inflammatory products to treat pigs with lameness. While both farmers and veterinarians gave similar pain scores overall, farmers rated gastrointestinal disease as more painful and conversely veterinarians scored lameness higher. Female and younger respondents gave higher pain scores than males and older respondents. Overall, farmers and veterinarians had a positive attitude towards pain relief in pigs with the majority agreeing that animals recovered more promptly when pain relief was administered. Most farmers agreed that the recognition and management of pain is an important part of pig husbandry, and many expressed an interest in finding out more about identifying pain in this species as well as the treatment options available. The study highlighted potential barriers to the increased application of pain relief in pigs in that almost one-third of veterinarians and two-thirds of farmers did not agree that they discussed pain management with each other, while other respondents indicated that they found it difficult to recognise pain in pigs, and did not know how to treat it appropriately. Copyright © 2014 Elsevier Ltd. All rights reserved.

Equal pain – Unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

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Michael Lukas Meier

2014-07-01

Full Text Available Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS applied to the right maxillary canine (UCS-c versus the right tibia (UCS-t. For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+. Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were 1 skin conductance changes and 2 time-dependent brain activity (BOLD responses in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex and medial prefrontal cortex.A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point towards a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending Facilitatory Pathway in Rats with Inflammatory Pain

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Man-Li Hu

2017-01-01

Full Text Available The mitogen-activated protein kinases (MAPKs, especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG, the rostral ventromedial medulla (RVM, and the spinal cord dorsal horn (SCDH. However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT, paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR cells were measured before (0 h and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

Chronic female pelvic pain

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Gaurab Maitra

2013-01-01

Full Text Available Chronic pelvic pain (CPP is defined as nonmalignant pain perceived in the structures related to the pelvis that has been present for more than 6 months or a non acute pain mechanism of shorter duration. Pain in the pelvic region can arise from musculoskeletal, gynaecological, urologic, gastrointestinal and or neurologic conditions. Key gynaecological conditions that contribute to CPP include pelvic inflammatory disease (PID, endometriosis, adnexa pathologies (ovarian cysts, ovarian remnant syndrome, uterine pathologies (leiomyoma, adenomyosis and pelvic girdle pain associated with pregnancy. Several major and minor sexually transmitted diseases (STD can cause pelvic and vulvar pain. A common painful condition of the urinary system is Interstitial cystitis(IC. A second urologic condition that can lead to development of CPP is urethral syndrome. Irritable bowel syndrome (IBS is associated with dysmenorrhoea in 60% of cases. Other bowel conditions contributing to pelvic pain include diverticular disease,Crohn′s disease ulcerative colitis and chronic appendicitis. Musculoskeletal pathologies that can cause pelvic pain include sacroiliac joint (SIJ dysfunction, symphysis pubis and sacro-coccygeal joint dysfunction, coccyx injury or malposition and neuropathic structures in the lower thoracic, lumbar and sacral plexus. Prolonged pelvic girdle pain, lasting more than 6 months postpartum is estimated in 3% to 30% of women. Nerve irritation or entrapment as a cause of pelvic pain can be related to injury of the upper lumbar segments giving rise to irritation of the sensory nerves to the ventral trunk or from direct trauma from abdominal incisions or retractors used during abdominal surgical procedures. Afflictions of the iliohypogastric, ilioinguinal, genitofemoral, pudendal and obturator nerves are of greatest concern in patients with pelvic pain. Patient education about the disease and treatment involved is paramount. A knowledge of the differential

Vitamin D for the treatment of chronic painful conditions in adults.

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Straube, Sebastian; Derry, Sheena; Straube, Carmen; Moore, R Andrew

2015-05-06

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions. To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries. We included studies if they were randomised double-blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults. Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events. We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was

Investigating the Burden of Chronic Pain: An Inflammatory and Metabolic Composite

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Kimberly T. Sibille

2016-01-01

Full Text Available Background. Chronic pain is associated with increased morbidity and mortality, predominated by cardiovascular disease and cancer. Investigating related risk factor measures may elucidate the biological burden of chronic pain. Objectives. We hypothesized that chronic pain severity would be positively associated with the risk factor composite. Methods. Data from 12,982 participants in the 6th Tromsø study were analyzed. Questionnaires included demographics, health behaviors, medical comorbidities, and chronic pain symptoms. The risk factor composite was comprised of body mass index, fibrinogen, C-reactive protein, and triglycerides. Chronic pain severity was characterized by frequency, intensity, time/duration, and total number of pain sites. Results. Individuals with chronic pain had a greater risk factor composite than individuals without chronic pain controlling for covariates and after excluding inflammation-related health conditions (p<0.001. A significant “dose-response” relationship was demonstrated with pain severity (p<0.001. In individuals with chronic pain, the risk factor composite varied by health behavior, exercise, lower levels and smoking, and higher levels. Discussion. The risk factor composite was higher in individuals with chronic pain, greater with increasing pain severity, and influenced by health behaviors. Conclusions. Identification of a biological composite sensitive to pain severity and adaptive/maladaptive behaviors would have significant clinical and research utility.

Pain and pain mechanisms in patients with inflammatory arthritis

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Rifbjerg-Madsen, S; Christensen, A W; Christensen, R

2017-01-01

completed the PDQ (RA: 3,826, PsA: 1,180, SpA: 1,093). 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18....... The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation. METHODS: The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology......28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment....

Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).

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Park, Thomas J; Lu, Ying; Jüttner, René; Smith, Ewan St J; Hu, Jing; Brand, Antje; Wetzel, Christiane; Milenkovic, Nevena; Erdmann, Bettina; Heppenstall, Paul A; Laurito, Charles E; Wilson, Steven P; Lewin, Gary R

2008-01-01

In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber.

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Thomas J Park

2008-01-01

Full Text Available In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception.

Conditioned pain modulation is affected by occlusion cuff conditioning stimulus intensity, but not duration.

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Smith, A; Pedler, A

2018-01-01

Various conditioned pain modulation (CPM) methodologies have been used to investigate diffuse noxious inhibitory control pain mechanisms in healthy and clinical populations. Occlusion cuff parameters have been poorly studied. We aimed to investigate whether occlusion cuff intensity and/or duration influenced CPM magnitudes. We also investigated the role of physical activity levels on CPM magnitude. Two studies were performed to investigate the role of intensity and duration of occlusion cuff conditioning stimulus on test stimulus (tibialis anterior pressure pain thresholds). In Study 1, conditioning stimulus intensity of 2/10 or 5/10 (duration CPM magnitude. In Study 1, 27 healthy volunteers (mean ± SD: 24.9 years (±4.5); eight female) demonstrated that an occlusion cuff applied to the upper arm eliciting 5/10 local pain resulted in a significant (mean ± SD: 17% ± 46%) increase in CPM magnitude, when compared to 2/10 intensity (-3% ± 38%, p = 0.026), whereas in Study 2, 25 healthy volunteers (22.5 years (±2.7); 13 female) demonstrated that 3 min of 2/10 CS intensity did not result in a significant change in CPM (p = 0.21). There was no significant relationship between physical activity levels and CPM in either study (p > 0.22). This study demonstrated that an occlusion cuff of 5/10 conditioning stimulus intensity, when compared to 2/10, significantly increased CPM magnitude. Maintaining 2/10 conditioning stimulus for 3 min did not increase CPM magnitude. Dysfunctional conditioned pain modulation (CPM) has been associated with poor health outcomes. Various factors can influence CPM outcomes. The role of occlusion cuff conditioning stimulus intensity and duration has not been previously investigated. Intensity (5/10), but not duration of lower intensity (2/10) conditioning stimulus, affects CPM magnitude. © 2017 European Pain Federation - EFIC®.

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

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Sakin, Y S; Dogrul, A; Ilkaya, F; Seyrek, M; Ulas, U H; Gulsen, M; Bagci, S

2015-07-01

Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain. © 2015 John Wiley & Sons Ltd.

Short-term cortical plasticity induced by conditioning pain modulation

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Egsgaard, Line Lindhardt; Buchgreitz, Line; Wang, Li

2012-01-01

To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical stimulat......To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical......, and after homotopic and heterotopic CPM versus control. Peak latencies at N100, P200, and P300 were extracted and the location/strength of corresponding dipole current sources and multiple dipoles were estimated. Homotopic CPM caused hypoalgesia (P = 0.032, 30.6% compared to baseline) to electrical...... stimulation. No cortical changes were found for homotopic CPM. A positive correlation at P200 between electrical pain threshold after tonic pain and the z coordinate after tonic pain (P = 0.032) was found for homotopic CPM. For heterotopic CPM, no significant hypoalgesia was found and a dipole shift of the P...

Sex differences in the relationship between maternal fear of pain and children's conditioned pain modulation

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Evans S

2013-03-01

Full Text Available Subhadra Evans, Laura C Seidman, Kirsten C Lung, Lonnie K Zeltzer, Jennie C TsaoPediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USABackground: Parental behaviors, emotions, and cognitions are known to influence children's response to pain. However, prior work has not tested the association between maternal psychological factors and children's responses to a conditioned pain modulation (CPM task. CPM refers to the reduction in perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals.Methods: The present study examined sex differences in the association between maternal anxiety about pain and children's CPM responses in 133 healthy children aged 8–17 years. Maternal pain anxiety was assessed using the Pain Anxiety Symptoms Scale-20. In addition to the magnitude of CPM, children's anticipatory anxiety and pain-related fear of the CPM task were measured.Results: Sequential multiple linear regression revealed that even after controlling for child age and general maternal psychological distress, greater maternal pain anxiety was significantly related to greater CPM anticipatory anxiety and pain-related fear in girls, and to less CPM (ie, less pain inhibition in boys.Conclusion: The findings indicate sex-specific relationships between maternal pain anxiety and children's responses to a CPM task over and above that accounted for by the age of the child and the mother's general psychological distress.Keywords: diffuse noxious inhibitory controls, pediatric pain, mother-child relationship, cold pressor, pressure pain, laboratory pain

Conditioned pain modulation dampens the thermal grill illusion.

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Harper, D E; Hollins, M

2017-10-01

The thermal grill illusion (TGI) refers to the perception of burning heat and often pain that arises from simultaneous cutaneous application of innocuous warm and cool stimuli. This study utilized conditioned pain modulation (CPM) to help elucidate the TGI's underlying neural mechanisms, including the debated role of ascending nociceptive signals in generating the illusion. To trigger CPM, subjects placed the left hand in noxious cold (6 °C) water before placing the right volar forearm onto a thermal grill. Lower pain and unpleasantness ratings of the grill in this CPM run compared to those in a control run (i.e. 33 °C water) were taken as evidence of CPM. To determine whether CPM reduces noxious heat pain and illusory heat pain equally, an experimental group of subjects rated pain and unpleasantness of a grill consisting of innocuous alternating warm (42 °C) and cool (18 °C) bars, while a control group rated a grill with all bars controlled to a noxious temperature (45 °C). CPM produced significant and comparable reductions in pain, unpleasantness and perceived heat of both noxious heat and the TGI. This result suggests that the TGI results from signals in nociceptive dorsal horn convergent neurons, since CPM involves descending inhibition with high selectivity for this neuronal population. More broadly, CPM's ability to produce a shift in perceived thermal sensation of both noxious heat and the TGI from 'hot' to 'warm' implies that nociceptive signals generated by a cutaneous stimulus can contribute to its perceived thermal intensity. Conditioned pain modulation reduces the perceived painfulness, unpleasantness and heat of the thermal grill illusion and noxious heat similarly. The results have important theoretical implications for both types of pain. © 2017 European Pain Federation - EFIC®.

Anti-hyperalgesic activity of the aqueous and methanol extracts of the leaves of Pittosporum mannii Hook on CFA-induced persistent inflammatory pain.

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Wandji, Bibiane Aimée; Bomba, Francis Desire Tatsinkou; Nkeng-Efouet, Pepin Alango; Piegang, Basile Nganmegne; Kamanyi, Albert; Nguelefack, Télesphore Benoît

2018-02-01

Previous study showed that aqueous (AEPM) and methanol (MEPM) extracts from the leaves of Pittosporum mannii have analgesic effects in acute pain models. The present study evaluates the acute and chronic anti-hypernociceptive and anti-inflammatory effects of AEPM and MEPM in a model of persistent inflammatory pain. The third day after induction of inflammatory pain by subplantar injection of 100 µL of CFA in Wistar rats, AEPM and MEPM were administered orally (75, 150 and 300 mg/kg/day) and their anti-hyperalgesic and anti-inflammatory effects were follow in acute (1-24 h) and chronic (for 14 days) treatments. At the end of the chronic treatment, oxidative stress and liver parameters were assessed. Effects of plant extracts were also evaluated on nociception induced by Phorbol 12-Myristate 13-Acetate (PMA) and 8-bromo 3',5'-cAMP (8-Br-cAMP) in mice. AEPM and MEPM significantly reversed the mechanical hyperalgesia caused by CFA in acute and chronic treatment. Moreover, AEPM and MEPM also significantly reduced the nociception caused by PMA (60%) and 8-Br-cAMP (87%). Nevertheless, AEPM and MEPM failed to inhibit the paw edema caused by CFA. Plant extracts significantly reduced the nitric oxide content in the spinal cord and the plasmatic concentration of alanine aminotransferase. MEPM also significantly increased the glutathione content in the spinal cord. AEPM and MEPM given orally are effective in inhibiting mechanical hyperalgesia in persistent inflammatory pain caused by CFA. Their mechanisms of action seem to involve an interaction with PKC, PKA and nitric oxide pathways. These extracts might be devoid of hepatotoxic effects.

Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch.

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Lionberger, David R; Brennan, Michael J

2010-11-10

The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP) in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978-2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5-1.9). In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs). The physical-chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions.

Inflammatory Mediators and Pain in the First Year After Acute Episode of Low-Back Pain in Elderly Women: Longitudinal Data from Back Complaints in the Elders-Brazil.

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Queiroz, Bárbara Zille; Pereira, Daniele Sirineu; Rosa, Nayza Maciel de Britto; Lopes, Renata Antunes; Andrade, André Gustavo Pereira; Felício, Diogo Carvalho; Jardim, Renata Muniz Freire Vinhal Siqueira; Leopoldino, Amanda Aparecida Oliveira; Silva, Juscélio Pereira; Pereira, Leani Souza Máximo

2017-08-01

The aims of this study were to determine the course of plasma levels of inflammatory mediators (interleukin 6 [IL-6], tumor necrosis factor α [TNF-α], soluble TNF receptor 1 [sTNF-R1]) and the severity of low-back pain (LBP) over 6 to 12 months after an acute episode of LBP in elderly women and to establish an association between inflammatory mediators and LBP recovery. This was a longitudinal study of a subsample (155 elderly women with acute LBP, aged ≥65 years) of the international Back Complaints in the Elders cohort study. Plasma levels of IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays and pain severity using the numerical pain scale. There was a decrease in the severity of LBP (P = 0.033) and in the levels of IL-6 and TNF-α (P relief at the 12-month follow-up was 2.22 times higher in elderly women who had low levels of IL-6 (<1.58 pg/mL) at baseline. Our findings showed a relationship between inflammation and LBP by establishing that low IL-6 plasma levels preceded outcome (LBP recovery), supporting the concept that proinflammatory cytokines promote pain.

Modulation of itch by conditioning itch and pain stimulation in healthy humans

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Andersen, Hjalte Holm; van Laarhoven, Antoinette I. M.; Elberling, Jesper

2017-01-01

Little is known about endogenous descending control of itch. In chronic pain, descending pain inhibition is reduced as signified by lowered conditioned pain modulation (CPM). There are indications that patients with chronic itch may also exhibit reduced endogenous descending inhibition of itch......-evoked itch, while the test stimuli were electrical stimulation paradigms designed to evoke itch or pain. Pain was significantly reduced (CPM-effect) by the conditioning pain stimulus (p

A novel paradigm to evaluate conditioned pain modulation in fibromyalgia

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Schoen CJ

2016-09-01

Full Text Available Cynthia J Schoen,1,* Jacob N Ablin,2,* Eric Ichesco,1 Rupal J Bhavsar,3 Laura Kochlefl,1 Richard E Harris,1 Daniel J Clauw,1 Richard H Gracely,4 Steven E Harte1 1Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA; 2Institute of Rheumatology, Tel Aviv Suorasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Neurology, University of Pennsylvania, Philadelphia, PA, 4Department of Endodontics, University of North Carolina – Chapel Hill, Chapel Hill, NC, USA *These authors contributed equally to this work Introduction: Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM. The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associated with various chronic pain conditions. Current methods used to assess CPM vary widely, and interest in CPM method development remains strong. Here, we evaluated a novel method for assessing CPM in healthy controls and fibromyalgia (FM patients using thumb pressure as both a test and conditioning stimulus.Methods: Sixteen female FM patients and 14 matched healthy controls underwent CPM testing with thumbnail pressure as the test stimulus, and either cold water or noxious pressure as the conditioning stimulus. CPM magnitude was evaluated as the difference in pain rating of the test stimulus applied before and during the conditioning stimulus.Results: In healthy controls, application of either pressure or cold water conditioning stimulation induced CPM as evidenced by a significant reduction in test stimulus pain rating during conditioning (P=0.007 and P=0.021, respectively. In contrast, in FM patients, neither conditioning stimulus induced a significant CPM effect P-values >0

Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: implications for pain and memory.

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Rahn, Elizabeth J; Guzman-Karlsson, Mikael C; David Sweatt, J

2013-10-01

Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla. Copyright © 2013 Elsevier Inc. All rights reserved.

Provoked Vestibulodynia and the Health Care Implications of Comorbid Pain Conditions.

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Lester, Robynn A; Brotto, Lori A; Sadownik, Leslie A

2015-11-01

Sexual pain secondary to provoked vestibulodynia (PVD) is a chronic pain condition affecting up to 16% of women. Women with PVD may report other chronic pain conditions. The goals of this study were (1) to identify the prevalence of self-reported chronic pain conditions in a sample of women with a diagnosis of PVD and seeking treatment, and (2) to compare demographic and clinical characteristics and health care needs of women with PVD alone and women with PVD and two or more self-reported chronic pain conditions. We assessed the characteristics of 236 women with PVD alone and 55 women with PVD and comorbid chronic pain using a standardized questionnaire, the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Pain Vigilance and Awareness Questionnaire, and the Female Sexual Distress Scale. Compared with women with PVD alone, women with PVD and other concurrent pain reported a significantly longer duration of pain, pain radiating to other parts of the vulva, and pain interfering in a variety of daily activities. This group was also significantly more likely to have seen more gynaecologists, and to have had more office visits with their gynaecologist than women with PVD alone. They were more likely to have tried anticonvulsants, antidepressants, and stress/relaxation therapy for their PVD and were also more likely to have allergies and skin sensitivities. Finally, this group of women had higher symptoms of depression, trait anxiety, and showed a trend towards more pain vigilance. Taken together, these findings suggest that physicians caring for women with PVD and concurrent chronic pain must be alert to the potentially greater health needs among this subsample of women.

Anorectal and Pelvic Pain.

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Bharucha, Adil E; Lee, Tae Hee

2016-10-01

Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Orofacial pain conditions

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Pedersen, Anne Marie Lynge; Forssell, Heli; Grinde, Bjørn

2016-01-01

Pain of the oral mucosa is a common accompanying symptom of various oral mucosal lesions caused by local and systemic diseases. Pain of the oral mucosa is usually associated with a known cause of tissue damage, e.g. mucosal ulcer or erosion, and it generally responds to adequate treatment...... and dissolves after healing. Chronic pain, on the other hand, persists months and years after apparent tissue healing, and attempts to alleviate pain are challenging. Neuropathic pain occurs due to damage neurogenic structures in the peripheral and/or the central nervous system. It may occur in the absence...... of any obvious noxious stimuli, and in the oral mucosal, the pain is often described as tingling and burning. In the oral cavity, burning mouth syndrome (BMS) is presently considered to have neuropathic background. It is important for dental practitioners to have a clear understanding of the various...

Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients

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Petersen, Susanne G; Beyer, Nina; Hansen, Mette

2011-01-01

Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients.......Petersen SG, Beyer N, Hansen M, Holm L, Aagaard P, Mackey AL, Kjaer M. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients....

The prevalence of radiographic sacroiliitis in patients affected by inflammatory bowel disease with inflammatory low back pain

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A. Lo Nigro

2011-09-01

Full Text Available Inflammatory bowel diseases (IBD, are Crohn’s disease (CD or ulcerative colitis (UC, are frequently complicated by joint complaints with prevalence that varies between 10 and 28 %. The IBD related arthropathy may be expressed as peripheral arthritis or axial one frequently indistinguishable from the classical ankylosing spondylitis (AS. According to ESSG criteria for spondyloarthropathy, the presence of synovitis or the inflammatory back pain (IBP in IBD patients is diagnostic for spondyloarthropathy, but for diagnosis of as also radiological criteria must be fulfilled. There are few studies regarding the radiological prevalence of sacroiliitis in patients with IBD. We examined, by plain film radiograms of pelvis, 100 sacroiliac joints (SJ of 50 IBD patients with IBP. The New York (1984 SJ radiological score with gradation from 0 to 4 was applied. Total sacroiliac score (SJS was summarized between left and right side (from 0 to 8. Fourteen patients fulfilled New York modified criteria for AS and 8 patients had unilateral 2nd grade sacroiliitis. Only 4 of 14 AS patients (28% were HLA B27 positive. Thirty patients had localized IBP, 10 extended to buttock and 4 extended to sacrum. Sixteen patients had sciatica-like extension of back pain. A difference in SJS between left and right side were observed only in CD patients (1,3± 0,8 e 0,8± 0,9 respectively; p<0,05, but not in UC (1,5± 1,2 vs 1,5± 1,3; p=ns nor in total IBD patients (1,4± 1 vs 1,2± 1,2; p=ns. Total SJS was higher in UC respect CD, but not significantly (2,9± 2,3 vs 2,1± 1,5; p=ns. Our data confirm the importance of these symptoms in patients with IBD, who need to be carefully investigated also for these aspects.

Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain

Czech Academy of Sciences Publication Activity Database

Rivas-Ramirez, Paula; Gadotti, V. M.; Zamponi, G. W.; Weiss, Norbert

2017-01-01

Roč. 469, č. 10 (2017), s. 1325-1334 ISSN 0031-6768 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * pain * inflammatory pain * calcium channel blocker * surfen * DRG neuron Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 3.156, year: 2016

Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

Science.gov (United States)

Ji, Yan-Bo; Bo, Chun-Lu; Xue, Xiu-Juan; Weng, En-Ming; Gao, Guang-Chao; Dai, Bei-Bei; Ding, Kai-Wen; Xu, Cui-Ping

2017-12-01

Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. Copyright © 2017. Published by Elsevier Inc.

Inflammatory pain in experimental burns in man

DEFF Research Database (Denmark)

Pedersen, J L

2000-01-01

stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects......Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects...... demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model...

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)

NARCIS (Netherlands)

Sieper, J.; Van der Heijde, D.M.; Landewe, RB; Brandt, J.; Burgos-Vagas, R.; Collantes-Estevez, E.; Dijkmans, B.A.C.; Dougados, M.; Khan, M.M.; Leirisalo-Repo, M; van der Linden, S.C.; Maksymowych, W.P.; Mielants, H.; Olivieri, I.; Rudwaleit, M.

2009-01-01

Objective: Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Methods: Rheumatologists (n =

AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions.

Science.gov (United States)

Paice, Judith A; Mulvey, Matt; Bennett, Michael; Dougherty, Patrick M; Farrar, John T; Mantyh, Patrick W; Miaskowski, Christine; Schmidt, Brian; Smith, Thomas J

2017-03-01

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to develop the characteristics of an optimal diagnostic system. After the establishment of these characteristics, a working group consisting of clinicians and clinical and basic scientists with expertise in cancer and cancer-related pain was convened to generate core diagnostic criteria for an illustrative sample of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic cancer pain as models of pain related to a tumor) or its treatment (ie, chemotherapy-induced peripheral neuropathy). A systematic review and synthesis was conducted to provide evidence for the dimensions that comprise this cancer pain taxonomy. Future efforts will subject these diagnostic categories and criteria to systematic empirical evaluation of their feasibility, reliability, and validity and extension to other cancer-related pain syndromes. The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy provides consistent diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms for these potentially serious cancer pain conditions that can be extended and applied with other cancer

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS)

NARCIS (Netherlands)

Sieper, J.; van der Heijde, D.; Landewé, R.; Brandt, J.; Burgos-Vagas, R.; Collantes-Estevez, E.; Dijkmans, B.; Dougados, M.; Khan, M. A.; Leirisalo-Repo, M.; van der Linden, S.; Maksymowych, W. P.; Mielants, H.; Olivieri, I.; Rudwaleit, M.

2009-01-01

Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Rheumatologists (n = 13) who are experts

Bilobalide, a unique constituent of Ginkgo biloba, inhibits inflammatory pain in rats.

Science.gov (United States)

Goldie, Michelle; Dolan, Sharron

2013-08-01

Standardized Ginkgo biloba extract EGb 761 has been shown to inhibit inflammatory hyperalgesia in rats; however, the mechanism of action is not known. This study set out to investigate the anti-inflammatory and analgesic potential of bilobalide, a unique G. biloba constituent, in three well-characterized models of acute inflammatory pain. The effect of oral, intraplantar or intrathecal administration of bilobalide or drug-vehicle (0.25% agar; 10% ethanol in H2O) on responses to noxious thermal and mechanical stimulation of the hindpaw, and paw oedema were assessed in adult male Wistar rats before and after intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or after hindpaw incision (n=6-8/group). Oral administration of bilobalide (10-30 mg/kg) significantly inhibited thermal hyperalgesia in response to carrageenan, capsaicin and paw incision, independent of dose, with an efficacy similar to that of diclofenac. In the carrageenan model, mechanical hypersensitivity and paw oedema were also significantly reduced after treatment with bilobalide (10-30 mg/kg). Intrathecal administration of bilobalide (0.5-1 μg) inhibited carrageenan-induced thermal hyperalgesia, but had no effect on mechanical hypersensitivity or paw oedema (application≥2 μg induced adverse effects, precluding testing of higher doses). Intraplantar administration of bilobalide (30-100 μg) had no effect. These data show that bilobalide is a potent anti-inflammatory and antihyperalgesic agent, the therapeutic effects of which are mediated in part through a central site of action, and may account for the therapeutic action of the whole extract G. biloba.

Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM).

Science.gov (United States)

Tsukamoto, M; Petersen, K K; Mørch, C D; Arendt-Nielsen, L

2017-12-29

Aims Traditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM. Methods 20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, "0" represented "no pain", and "10" represented "maximal pain"). The pain detection threshold (PDT) was defined as "1" on the VAS scale. Results There was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.

Analgesic efficacy of CR4056, a novel imidazoline-2 receptor ligand, in rat models of inflammatory and neuropathic pain

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Ferrari F

2011-04-01

Full Text Available Flora Ferrari1, Simonetta Fiorentino1, Laura Mennuni1, Paolo Garofalo1, Ornella Letari1, Stefano Mandelli2, Antonio Giordani3, Marco Lanza1, Gianfranco Caselli11Department of Pharmacology and Toxicology; 2Department of Medicinal Chemistry; 3R&D Chemistry Drug Development and OS, Rottapharm S.p.A., Monza (MB, ItalyAbstract: Two decades of investigations have failed to unequivocally clarify the functions and the molecular nature of imidazoline-2 receptors (I2R. However, there is robust pharmacological evidence for the functional modulation of monoamino oxidase (MAO and other important enzyme activities by I2 site ligands. Some compounds of this class proved to be active experimental tools in preventing both experimental pain and opioid tolerance and dependence. Unfortunately, even though these compounds bind with high potency to central I2 sites, they fail to represent a valid clinical opportunity due to their pharmacokinetic, selectivity or side-effects profile. This paper presents the preclinical profile of a novel I2 ligand (2-phenyl-6-(1H-imidazol-1ylquinazoline; [CR4056] that selectively inhibits the activity of human recombinant MAO-A in a concentration-dependent manner. A sub-chronic four day oral treatment of CR4056 increased norepinephrine (NE tissue levels both in the rat cerebral cortex (63.1% ± 4.2%; P<0.05 and lumbar spinal cord (51.3% ± 6.7%; P < 0.05. In the complete Freund's adjuvant (CFA rat model of inflammatory pain, CR4056 was found to be orally active (ED50 = 5.8 mg/kg, by mouth [p.o.]. In the acute capsaicin model, CR4056 completely blocked mechanical hyperalgesia in the injured hind paw (ED50 = 4.1 mg/kg, p.o.; ED100 = 17.9 mg/kg, p.o.. This effect was dose-dependently antagonized by the non-selective imidazoline I2/α2 antagonist idazoxan. In rat models of neuropathic pain, oral administration of CR4056 significantly attenuated mechanical hyperalgesia and allodynia. In summary, the present study suggests a novel

Utilization of Samarium-153 in bone pain and bone tumours in dog

International Nuclear Information System (INIS)

Martin, V. de; Marques, F.L.N.; Okamoto, M.; Guimaraes, M.I.C.C.; Dias-Neto, A.; Fonseca, A.C.

1997-01-01

Full text: The experimental unit of of Centro de Medicina Nuclear of the University of Sao Paulo is working on the utilization of Sm-153-EDTMP, produced by IPEN/CNEN-SP (Brazil), for the treatment of bone pain due either inflammatory process or bone tumours spontaneously developed in dogs. The effect of the injection of the radiopharmaceutical (37 MBq/kg) were analysed by observing the animal behavior against the pain and the evolution of the clinical picture of the inflammatory process. The cases where tumours were diagnosed, bone scintigraphy was performed to follow-up the evolution of those tumours. Preliminary observations indicated that, especially in inflammatory process due to disc spondylitis, there was an improvement concerning pain and consequently a better condition of the life for those animals. Bone tumours even being more difficult to evaluate, have shown a favorable evolution concerning the reduction of pain and consequently the increase in the life span of the animals

Botulinum Toxin Type A—A Modulator of Spinal Neuron–Glia Interactions under Neuropathic Pain Conditions

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Ewelina Rojewska

2018-04-01

Full Text Available Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A is used to treat a variety of clinical diseases associated with pain. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This review addresses the effects of BoNT/A on the relationship between glia and neurons under neuropathic pain. The inhibitory action of BoNT/A on synaptic vesicle fusion that blocks the release of miscellaneous pain-related neurotransmitters is known. However, increasing evidence suggests that the analgesic effect of BoNT/A is mediated through neurons and glial cells, especially microglia. In vitro studies provide evidence that BoNT/A exerts its anti-inflammatory effect by diminishing NF-κB, p38 and ERK1/2 phosphorylation in microglia and directly interacts with Toll-like receptor 2 (TLR2. Furthermore, BoNT/A appears to have no more than a slight effect on astroglia. The full activation of TLR2 in astroglia appears to require the presence of functional TLR4 in microglia, emphasizing the significant interaction between those cell types. In this review, we discuss whether and how BoNT/A affects the spinal neuron–glia interaction and reduces the development of neuropathy.

Functional abdominal pain.

Science.gov (United States)

Grover, Madhusudan; Drossman, Douglas A

2010-10-01

Functional abdominal pain syndrome (FAPS) is a relatively less common functional gastrointestinal (GI) disorder defined by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods (Drossman Gastroenterology 130:1377-1390, 2006), which points to a more centrally targeted (spinal and supraspinal) basis for the symptoms. However, FAPS is frequently confused with irritable bowel syndrome and other functional GI disorders in which abdominal pain is associated with eating and bowel movements. FAPS also differs from chronic abdominal pain associated with entities such as chronic pancreatitis or chronic inflammatory bowel disease, in which the pain is associated with peripherally acting factors (eg, gut inflammation or injury). Given the central contribution to the pain experience, concomitant psychosocial disturbances are common and strongly influence the clinical expression of FAPS, which also by definition is associated with loss of daily functioning. These factors make it critical to use a biopsychosocial construct to understand and manage FAPS, because gut-directed treatments are usually not successful in managing this condition.

Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

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Can Zhang

Full Text Available Painful neuropathy (PN is a prevalent condition in patients with metabolic syndrome (MetS. However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN remain unclear. In the current study, high-fat-fed mice (HF mice were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF-α, and interleukin (IL-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

Peculiarities of Abdominal Pain Syndrome in Patients with Functional and Inflammatory Bowel Diseases and Methods of Its Correction

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A.E. Dorofeiev

2014-11-01

Full Text Available Objective of this study was to evaluate peculiarities of abdominal pain syndrome in patients with irritable bowel syndrome (IBS and inflammatory bowel disease (IBD and to assess efficacy of Enterospasmil in complex therapy of these patients. 120 patients with IBS and 35 patients with IBD were examined. Age of patients varied from 18 to 65 years. Abdominal pain syndrome was detected in all patients with IBS and IBD. In examined patients we have detected predominantly variable, without irradiation, often of blunt, aching nature, lasting more than 3 hours, with moderate intensity. Enterospasmil is an effective drug for abdominal pain relief in patients with IBS and IBD and can be used in complex therapy of these patients.

Topical nonsteroidal anti-inflammatory drugs for the treatment of pain due to soft tissue injury: diclofenac epolamine topical patch

Directory of Open Access Journals (Sweden)

David R Lionberger

2010-11-01

Full Text Available David R Lionberger1, Michael J Brennan21Southwest Orthopedic Group, Houston, TX, USA; 2Department of Medicine, Bridgeport Hospital, Bridgeport, CT, USAAbstract: The objective of this article is to review published clinical data on diclofenac epolamine topical patch 1.3% (DETP in the treatment of acute soft tissue injuries, such as strains, sprains, and contusions. Review of published literature on topical nonsteroidal anti-inflammatory drugs (NSAIDs, diclofenac, and DETP in patients with acute soft tissue injuries was included. Relevant literature was identified on MEDLINE using the search terms topical NSAIDs, diclofenac, diclofenac epolamine, acute pain, sports injury, soft tissue injury, strain, sprain, and contusion, and from citations in retrieved articles covering the years 1978–2008. Review of published, randomized clinical trials and meta-analyses shows that topical NSAIDs are significantly more effective than placebo in relieving acute pain; the pooled average relative benefit was 1.7 (95% confidence interval, 1.5–1.9. In a limited number of comparisons, topical and oral NSAIDs provided comparable pain relief, but the use of topical agents produced lower plasma drug concentrations and fewer systemic adverse events (AEs. The physical–chemical properties of diclofenac epolamine make it well suited for topical use. In patients with acute soft tissue injuries treated with DETP, clinical data report an analgesic benefit within hours of the first application, and significant pain relief relative to placebo within 3 days. Moreover, DETP displayed tolerability comparable with placebo; the most common AEs were pruritus and other application site reactions. Review of published literature suggests that DETP is generally safe and well tolerated, clinically efficacious, and a rational treatment option for patients experiencing acute pain associated with strains, sprains, and contusions, and other localized painful conditions

Biomarkers for Musculoskeletal Pain Conditions: Use of Brain Imaging and Machine Learning.

Science.gov (United States)

Boissoneault, Jeff; Sevel, Landrew; Letzen, Janelle; Robinson, Michael; Staud, Roland

2017-01-01

Chronic musculoskeletal pain condition often shows poor correlations between tissue abnormalities and clinical pain. Therefore, classification of pain conditions like chronic low back pain, osteoarthritis, and fibromyalgia depends mostly on self report and less on objective findings like X-ray or magnetic resonance imaging (MRI) changes. However, recent advances in structural and functional brain imaging have identified brain abnormalities in chronic pain conditions that can be used for illness classification. Because the analysis of complex and multivariate brain imaging data is challenging, machine learning techniques have been increasingly utilized for this purpose. The goal of machine learning is to train specific classifiers to best identify variables of interest on brain MRIs (i.e., biomarkers). This report describes classification techniques capable of separating MRI-based brain biomarkers of chronic pain patients from healthy controls with high accuracy (70-92%) using machine learning, as well as critical scientific, practical, and ethical considerations related to their potential clinical application. Although self-report remains the gold standard for pain assessment, machine learning may aid in the classification of chronic pain disorders like chronic back pain and fibromyalgia as well as provide mechanistic information regarding their neural correlates.

A systematic review assessing non-pharmacological conservative treatment studies for people with non-inflammatory multi-joint pain: clinical outcomes and research design considerations.

Science.gov (United States)

Comer, C; Smith, T O; Drew, B; Raja, R; Kingsbury, S R; Conaghan, Philip G

2018-03-01

To systematically review the evidence to determine the clinical outcomes and the important methodological quality features of interventional studies on adults with non-inflammatory multi-joint pain (MJP). Systematic search of published and unpublished literature using the databases: AMED, CINAHL, MEDLINE, EMBASE, psycINFO, SPORTDiscus, PEDro, OpenGrey, the EU Clinical Trials Register, World Health Organization International Clinical Trial Registry Platform, ClinicalTrials.gov and the ISRCTN registry (search: inception to 19th October 2017). All papers reporting the clinical outcomes of non-pharmacological interventions for people with non-inflammatory MJP were included. Studies were critically appraised using the Downs and Black Critical Appraisal and the TIDieR reporting checklists. Data were analysed using a Best Evidence Synthesis approach. From 3824 citations, four papers satisfied the eligibility criteria. Three studies reported outcomes from multidisciplinary rehabilitation programmes and one study reported the findings of a spa therapy intervention. All interventions significantly improved pain, function and quality of life in the short-term. There was limited reporting of measures for absenteeism, presenteeism and psychosocial outcomes. The evidence was 'weak', and due to a lack of controlled trials, there is limited evidence to ascertain treatment effectiveness. Design consideration for future trials surround improved reporting of participant characteristics, interventions and the standardisation of core outcome measures. There is insufficient high-quality trial data to determine the effectiveness of treatments for non-inflammatory MJP. Given the significant health burden which this condition presents on both individuals and wider society, developing and testing interventions and accurately reporting these, should be a research priority. Registration PROSPERO (CRD42013005888).

Recommendations on practice of conditioned pain modulation (CPM) testing.

Science.gov (United States)

Yarnitsky, D; Bouhassira, D; Drewes, A M; Fillingim, R B; Granot, M; Hansson, P; Landau, R; Marchand, S; Matre, D; Nilsen, K B; Stubhaug, A; Treede, R D; Wilder-Smith, O H G

2015-07-01

Protocols for testing conditioned pain modulation (CPM) vary between different labs/clinics. In order to promote research and clinical application of this tool, we summarize the recommendations of interested researchers consensus meeting regarding the practice of CPM and report of its results. © 2014 European Pain Federation - EFIC®

Knowledge of Housewives Regarding Non Steroid Anti Inflammatory Drug Use on Joint Pain in Hegarmanah Village Jatinangor

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Adi Mulyono Gondopurwanto

2016-03-01

Full Text Available Background: Joint pain is frequently found in daily life activities. The prevalence of joint pain increases within the age. One of the medicine used for joint pain is non-steroidal anti-inflammatory drug (NSAID. In connection with inappropriate usage and their side effects, this study aimed to seek the extent ofhousewives’ knowledge on the use of NSAID for joint pain in Hegarmanah village, Jatinangor subdistrict. Methods: This cross-sectional descriptive study was conducted in October 2013 to the housewives resided in Hegarmanah village, Jatinangor subdistrict, West Java. Questionaire sheet was distributed to each of 110 housewives that had been stratifiedly with randomized sample. The questionaire contained identity, age, education level, and knowledge of NSAID in related to joint pain. Results: Based on the data collected, 73 subjects had adequate level of the knowledge and 37 subjects were in a poor level of the knowledge. The proportion of respondents who knew that joint pain was the pain occurs in the joint was 99.1%, the proportion of respondents who knew that the pain relieving drugs are called NSAID group was 40.9%, the proportion of respondents who knew that NSAID had a side-effect was 73.6%, and the proportion of respondents who knew that the side-effect of NSAID is abdominal pain was 61.8%. Conclusions: Most of the housewives in Hegarmanah Subdistrict have adequate knowledge in the use ofNSAID for joint pain relief.

Habituating pain: Questioning pain and physical strain as inextricable conditions in the construction industry

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Jeppe Z.N. Ajslev

2013-09-01

Full Text Available In this article, we investigate the relations between discursive practices within the Danish construction industry and the perceived pain, physical deterioration, and strain affecting the construction workers. Of central importance is the widely accepted hegemonic discourse on physical strain and pain as unavoidable conditions in construction work. Based on 32 semi-structured interviews performed in eight case studies within four different construction professions, workers’ descriptions of physical strain and its relation to the organizational and social context are analyzed through concepts of subject positioning in discursive practice and a focus on power relations. The analysis shows that workers and employers reproduce certain types of traditional working class masculinities and search for high-pace productive working rhythms, which in combination with economic incentives common within the industry reproduce physical strain and the habituation of pain as unquestioned conditions in construction work. The understanding of this mutual reinforcement of the necessity of physically straining, painful, high-paced construction work provides fruitful perspectives on the overrepresentation of musculoskeletal deterioration within construction work and also sheds light on some of the difficulties in addressing and changing occupational health and safety practices in the construction industry.

Learning to predict and control harmful events: chronic pain and conditioning.

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Vlaeyen, Johan W S

2015-04-01

Pain is a biologically relevant signal and response to bodily threat, associated with the urge to restore the integrity of the body. Immediate protective responses include increased arousal, selective attention, escape, and facial expressions, followed by recuperative avoidance and safety-seeking behaviors. To facilitate early and effective protection against future bodily threat or injury, learning takes place rapidly. Learning is the observable change in behavior due to events in the internal and external environmental and includes nonassociative (habituation and sensitization) and associative learning (Pavlovian and operant conditioning). Once acquired, these knowledge representations remain stored in memory and may generalize to perceptually or functionally similar events. Moreover, these processes are not just a consequence of pain; they may directly influence pain perception. In contrast to the rapid acquisition of learned responses, their extinction is slow, fragile, context dependent and only occurs through inhibitory processes. Here, we review features of associative forms of learning in humans that contribute to pain, pain-related distress, and disability and discuss promising future directions. Although conditioning has a long and honorable history, a conditioning perspective still might open new windows on novel treatment modalities that facilitate the well-being of individuals with chronic pain.

Silencing of FKBP51 alleviates the mechanical pain threshold, inhibits DRG inflammatory factors and pain mediators through the NF-kappaB signaling pathway.

Science.gov (United States)

Yu, Hong-Mei; Wang, Qi; Sun, Wen-Bo

2017-09-05

Neuropathic pain is chronic pain caused by lesions or diseases of the somatosensory system, currently available analgesics provide only temporal relief. The precise role of FK506 binding protein 51 (FKBP51) in neuropathic pain induced by chronic constriction injury (CCI) is not clear. The purpose of the present study was to investigate the effects and possible mechanisms of FKBP51 in neuropathic pain in the rat model of CCI. Our results showed that FKBP51 was obviously upregulated in a time-dependent manner in the dorsal root ganglion (DRG) of CCI rats. Additionally, silencing of FKBP51 remarkably attenuated mechanical allodynia and thermal hyperalgesia as reflected by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in CCI rats. Moreover, knockdown of FKBP51 reduced the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in the DRG of CCI rats. Furthermore, we revealed that inhibition of FKBP51 greatly suppressed the activation of the NF-kappaB (NF-κB) signaling in the DRG of CCI rats. Interestingly, similar to the FKBP51 siRNA (si-FKBP51), ammonium pyrrolidinedithiocarbamate (PDTC, an inhibitor of NF-κB) also alleviated neuropathic pain and neuro-inflammation, indicating that knockdown of FKBP51 alleviated neuropathic pain development of CCI rats by inhibiting the activation of NF-κB signaling pathway. Taken together, our findings indicate that FKBP51 may serve as a novel therapeutic target for neuropathic pain. Copyright © 2017. Published by Elsevier B.V.

Effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals

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Liang-Ying Luo

2017-08-01

Full Text Available Objective: To explore the effect of hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery on the synthesis of pain mediators, inflammatory mediator and oxygen free radicals. Methods: A total of 120 patients with fracture who underwent operation in the hospital between July 2014 and December 2016 were collected and divided into control group and observation group according to the random number table method, 60 cases in each group. Control group received morphine hydrochloride combined with ropivacaine for analgesia, observation group received hydromorphone hydrochloride combined with ropivacaine for analgesia, and the postoperative analgesia lasted for 48 h. The differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were compared between the two groups. Results: Immediately after operation, the differences in serum levels of pain mediators, inflammatory mediators and oxidative stress indexes were not statistically significant between the two groups. 48 h after operation, serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of both groups of patients were significantly lower than those immediately after operation while Cu-Zn SOD and GSH-Px levels were significantly higher than those immediately after operation, and serum PGE2, SP, β-EP, IL-6, MCP-1, HMGB-1 and MDA levels of observation group were significantly lower than those of control group while Cu-Zn SOD and GSH-Px levels were significantly higher than those of control group. Conclusion: Hydromorphone hydrochloride combined with ropivacaine for PCEA after orthopedic surgery is effective in alleviating pain and inhibiting systemic inflammatory response.

Socioeconomic conditions and number of pain sites in women

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Rannestad Toril

2012-03-01

Full Text Available Abstract Background Women in deprived socioeconomic situations run a high pain risk. Although number of pain sites (NPS is considered highly relevant in pain assessment, little is known regarding the relationship between socioeconomic conditions and NPS. Methods The study population comprised 653 women; 160 recurrence-free long-term gynecological cancer survivors, and 493 women selected at random from the general population. Demographic characteristics and co-morbidity over the past 12 months were assessed. Socioeconomic conditions were measured by Socioeconomic Condition Index (SCI, comprising education, employment status, income, ability to pay bills, self-perceived health, and satisfaction with number of close friends. Main outcome measure NPS was recorded using a body outline diagram indicating where the respondents had experienced pain during the past week. Chi-square test and forward stepwise logistic regression were applied. Results and Conclusion There were only minor differences in SCI scores between women with 0, 1-2 or 3 NPS. Four or more NPS was associated with younger age, higher BMI and low SCI. After adjustment for age, BMI and co-morbidity, we found a strong association between low SCI scores and four or more NPS, indicating that there is a threshold in the NPS count for when socioeconomic determinants are associated to NPS in women.

Efficacy of kilohertz-frequency and conventional spinal cord stimulation in rat models of different pain conditions.

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Song, Zhiyang; Viisanen, Hanna; Meyerson, Björn A; Pertovaara, Antti; Linderoth, Bengt

2014-04-01

The aim was to compare the effects of high-frequency spinal cord stimulation (HF-SCS) at subparesthetic intensity with conventional SCS in rat models of different types of pain. In addition, microrecordings of afferent activity in the dorsal columns during both types of SCS were performed to elucidate their mode of action. Miniature SCS electrodes were implanted in all rats. One group was submitted to the spared nerve injury procedure (SNI) and another to inflammatory pain after carrageenan injection into a hind paw. All animals were tested for hypersensitivity to normally innocuous tactile and thermal stimuli. One group of normal healthy rats was submitted to acute nociceptive (pinch, heat) pain. Microrecording of afferent activity in the gracile nucleus (GN) was performed in a group of nerve-lesioned rats responding to conventional SCS. HF-SCS at 500, 1,000, or 10,000 Hz at subparesthetic amplitudes produced similar reductions in hypersensitivity due to nerve lesion as did conventional SCS at 50 Hz. HF-SCS showed no effect on thermal pain. A trial to rescue non-responders to conventional SCS using HF-SCS was not successful. There were no effects either of conventional or of HF-SCS on acute or inflammatory pain. Conventional SCS produced massive activation in the GN but no activation during HF-SCS, though normal peripherally evoked afferent activity remained. Conventional SCS proved equally effective to HF-SCS in various pain models. As no activity is conveyed rostrally in subparesthetic HF-SCS, we hypothesize that its mechanisms of action are primarily segmental. © 2014 International Neuromodulation Society.

Anti-inflammatory and antinociceptive activities of Solenostemon monostachyus aerial part extract in mice

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Jude Fiom Okokon

2016-04-01

Full Text Available Objective: Solenostemon monostachyus is used in traditional medicine for the treatment of various ailments such as ulcer, hypertension, pains and inflammatory diseases. Evaluation of anti-inflammatory and analgesic activities of S. monostachyus aerial parts was carried out to ascertain its uses in traditional medicine. Materials and Methods: The aerial parts of S. monostachyus was cold extracted by soaking the dried powdered material in ethanol. The aerial parts crude extract (75 –225 mg/kg of  S. monostachyus was investigated for analgesic and anti-inflammatory activities using various experimental models; acetic acid, formalin and thermal- induced pains models for analgesic study and carrageenin, egg albumin and xylene – induced edema models for anti-inflammatory investigation. Results: The extract caused a significant (pConclusion: The anti-inflammatory and analgesic effects of this plant may in part be mediated through the chemical constituents of the plant and the results of the analgesic action suggest central and peripheral mechanisms. The findings of this work confirm the ethno medical use of this plant to treat inflammatory conditions.

Pharmacological potential of Maytenus species and isolated constituents, especially tingenone, for treatment of painful inflammatory diseases

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Clarice C. Veloso

Full Text Available ABSTRACT Uses of medicinal plants by people around the world significantly contribute and guide biologically active compounds research that can be useful in the combat against various diseases. Due to a great chemical and structural variety found in their vegetal structures it consolidates ethnopharmacology as an important science for the pharmaceutical section. Inserted in the diversity of medicinal plants, is the Maytenus genus, whose research has already revealed lots of isolated substances which are responsible for a great variety of biological activities, among which we cite analgesic and anti-inflammatory, for the treatment of inflammatory diseases such as rheumatoid arthritis, gastritis, ulcers and gastrointestinal disorders. The aim of this review article is to make a compendium of the Maytenus genus and its isolated chemical compounds, among them tingenone. The elucidation of its mechanism of action reveals promising sources for the development of new drugs specially targeted for the treatment of painful inflammatory diseases.

Pain management in patients with hidradenitis suppurativa

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Horvath, Barbara; Janse, Ineke C.; Sibbald, Gary R.

Hidradenitis suppurativa (HS) is a chronic, relapsing, and painful inflammatory disease. HS patients' quality of life is severely impaired, and this impairment correlates strongly with their pain. Pain in HS can be acute or chronic and has both inflammatory and noninflammatory origins. The purpose

α-blockers, antibiotics and anti-inflammatories have a role in the management of chronic prostatitis/chronic pelvic pain syndrome.

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Thakkinstian, Ammarin; Attia, John; Anothaisintawee, Thunyarat; Nickel, J Curtis

2012-10-01

Study Type - Therapy (systematic review) Level of Evidence 1a. What's known on the subject? and What does the study add? Individual clinical trials evaluating antibiotics, anti-inflammatories and α-blockers for the treatment of chronic prostatitis/chronic pelvic pain syndrome have shown only modest or even no benefits for patients compared with placebo, yet we continue to use these agents in selected patients with some success in clinical practice. This network meta-analysis of current evidence from all available randomized placebo-controlled trials with similar inclusion criteria and outcome measures shows that these '3-As' of chronic prostatitis/chronic pelvic pain syndrome treatment (antibiotics, anti-inflammatories and α-blockers) do offer benefits to some patients, particularly if we use them strategically in selected individuals. To provide an updated network meta-analysis mapping α-blockers, antibiotics and anti-inflammatories (the 3-As) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). • To use the results of this meta-analysis to comment on the role of the 3-As in clinical practice. We updated a previous review including only randomized controlled studies employing the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as one of the outcomes to compare treatment effects in CP/CPPS patients. • A longitudinal mixed regression model (network meta-analysis) was applied to indirectly assess multiple treatment comparisons (i.e. α-blockers, antibiotics, anti-inflammatory/immune modulation therapies, α-blockers plus antibiotics, and placebo). Nineteen studies (1669 subjects) were eligible for analysis. • α-blockers, antibiotics and anti-inflammatory/immune modulation therapies were associated with significant improvement in symptoms when compared with placebo, with mean differences of total CPSI of -10.8 (95% CI -13.2 to -8.3; P antibiotics resulted in the greatest CPSI difference (-13.6, 95% CI -16.7 to -10.6; P

Quality of Life in Arthritis Patients Using Nonsteroidal Anti-Inflammatory Drugs

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Ingela Wiklund

1999-01-01

Full Text Available Arthritis is a painful and disabling condition. To suppress the pain and the inflammatory process, patients are often chronic nonsteroidal anti-inflammatory drug (NSAID users. Chronic use of NSAIDs may induce peptic ulcer, dyspeptic problems and heartburn. Therefore, these patients are often provided with treatment to relieve and/or protect against gastrointestinal problems. Rheumatic disorders also affect a range of health-related quality of life domains. In one study, patients with NSAID-associated gastroduodenal lesions complained about lack of energy, sleep disturbances, emotional distress and social isolation in addition to pain and mobility limitations. The degree of distress and dysfunction differed markedly from scores in an unselected population. Clinical trial data suggest that acid-suppressing therapy with omeprazole is superior to therapy with misoprostol and ranitidine in healing gastroduodenal lesions and preventing abdominal pain, heartburn and indigestion symptoms during continued NSAID treatment. Because arthritic patients are severely incapacitated by their condition regarding most aspects of health-related quality of life, it is important to offer a treatment that is effective in healing and preventing NSAID-induced ulcers and gastrointestinal symptoms during continued NSAID treatment without further compromising the patients’ quality of life. Treatment with omeprazole once daily has been shown to be superior to that with ranitidine and misoprostol in this respect.

Hypoxic Stress and Inflammatory Pain Disrupt Blood-Brain Barrier Tight Junctions: Implications for Drug Delivery to the Central Nervous System.

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Lochhead, Jeffrey J; Ronaldson, Patrick T; Davis, Thomas P

2017-07-01

A functional blood-brain barrier (BBB) is necessary to maintain central nervous system (CNS) homeostasis. Many diseases affecting the CNS, however, alter the functional integrity of the BBB. It has been shown that various diseases and physiological stressors can impact the BBB's ability to selectively restrict passage of substances from the blood to the brain. Modifications of the BBB's permeability properties can potentially contribute to the pathophysiology of CNS diseases and result in altered brain delivery of therapeutic agents. Hypoxia and/or inflammation are central components of a number of diseases affecting the CNS. A number of studies indicate hypoxia or inflammatory pain increase BBB paracellular permeability, induce changes in the expression and/or localization of tight junction proteins, and affect CNS drug uptake. In this review, we look at what is currently known with regard to BBB disruption following a hypoxic or inflammatory insult in vivo. Potential mechanisms involved in altering tight junction components at the BBB are also discussed. A more detailed understanding of the mediators involved in changing BBB functional integrity in response to hypoxia or inflammatory pain could potentially lead to new treatments for CNS diseases with hypoxic or inflammatory components. Additionally, greater insight into the mechanisms involved in TJ rearrangement at the BBB may lead to novel strategies to pharmacologically increase delivery of drugs to the CNS.

Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

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Dong, Yingchun; Li, Pengfei; Ni, Yanhong; Zhao, Junjie; Liu, Zhiqiang

2014-01-01

Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs) and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA). Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs) following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO). Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase) alpha and CGRP (calcitonin gene-related peptide) were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.

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Yingchun Dong

Full Text Available Orofacial inflammatory pain is a difficult clinical problem, and the specific molecular mechanisms for this pain remain largely unexplained. The present study aimed to determine the differential expression of microRNAs (miRNAs and disclose the underlying role of miR-125a-3p in orofacial inflammatory pain induced by complete Freund's adjuvant (CFA. Thirty-two differentially expressed miRNAs were first screened using a microarray chip in ipsilateral trigeminal ganglions (TGs following CFA injection into the orofacial skin innervated by trigeminal nerve, and a portion of them, including miR-23a*, -24-2*, -26a, -92a, -125a-3p, -183 and -299 were subsequently selected and validated by qPCR. The target genes were predicted based on the miRWalk website and were further analyzed by gene ontology (GO. Further studies revealed miR-125a-3p expression was down-regulated, whereas both the expression of p38 MAPK (mitogen-activated protein kinase alpha and CGRP (calcitonin gene-related peptide were up-regulated in ipsilateral TGs at different time points after CFA injection compared with control. Furthermore, mechanistic study revealed that miR-125a-3p negatively regulates p38 alpha gene expression and is positively correlated with the head withdrawal threshold reflecting pain. Luciferase assay showed that binding of miR-125a-3p to the 3'UTR of p38 alpha gene suppressed the transcriptional activity, and overexpression of miR-125a-3p significantly inhibited the p38 alpha mRNA level in ND8/34 cells. Taken together, our results show that miR-125a-3p is negatively correlated with the development and maintenance of orofacial inflammatory pain via regulating p38 MAPK.

Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

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Moore, R A; Derry, S; Wiffen, P J; Straube, S; Aldington, D J

2015-10-01

Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICC®.

Chronic inflammatory pain: new molecules & mechanisms

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Willemen, H.L.D.M.

2013-01-01

Pain is an important self-protecting signal. The pain system detects and reacts to (withdrawal reflex) the presence of an acute potentially injurious stimulus such as heat, pressure, tissue damage or inflammation to avoid possible (further) tissue damage. However, after inflammation or tissue damage

Tamsulosin Monotherapy versus Combination Therapy with Antibiotics or Anti-Inflammatory Agents in the Treatment of Chronic Pelvic Pain Syndrome

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Tae Hyo Kim

2011-06-01

Full Text Available Purpose Chronic pelvic pain syndrome (CPPS is treated by use of various protocols. We compared tamsulosin monotherapy with tamsulosin in combination with antibiotics or anti-inflammatory agents and evaluated the efficacy of these treatments in patients with CPPS. Methods Patients (n=107 who were younger than 55 years and diagnosed with CPPS were randomly assigned to treatment with tamsulosin at 0.2 mg (group A, tamsulosin at 0.2 mg plus anti-inflammatory drugs (group B or tamsulosin at 0.2 mg plus antibiotics (group C daily. We applied the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI and the International Prostate Symptom Score (IPSS to evaluate 100 patients who were treated for 12 weeks (7 withdrew. Scores of the three groups were compared by analysis of variance and we also evaluated subscores, which included pain, voiding and quality of life (QoL. Results All three groups showed statistically significant decreases in NIH-CPSI score, IPSS and subscore scores (P<0.05. There were no statistically significant differences between the groups except for the QoL domain of the IPSS (group A vs. C; P<0.01. Conclusions Tamsulosin monotherapy for 12 weeks was effective for treating patients with CPPS, compared with combination therapy with antibiotics or anti-inflammatory drugs.

Effect of Eucalyptus Oil Inhalation on Pain and Inflammatory Responses after Total Knee Replacement: A Randomized Clinical Trial

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Yang Suk Jun

2013-01-01

Full Text Available Eucalyptus oil has been reported effective in reducing pain, swelling, and inflammation. This study aimed to investigate the effects of eucalyptus oil inhalation on pain and inflammatory responses after total knee replacement (TKR surgery. Participants were randomized 1 : 1 to intervention group (eucalyptus inhalation group or control group (almond oil inhalation group. Patients inhaled eucalyptus or almond oil for 30 min of continuous passive motion (CPM on 3 consecutive days. Pain on a visual analog scale (VAS, blood pressure, heart rate, C-reactive protein (CRP concentration, and white blood cell (WBC count were measured before and after inhalation. Pain VAS on all three days (P<.001 and systolic (P<.05 and diastolic (P=.03 blood pressure on the second day were significantly lower in the group inhaling eucalyptus than that inhaling almond oil. Heart rate, CRP, and WBC, however, did not differ significantly in the two groups. In conclusion, inhalation of eucalyptus oil was effective in decreasing patient's pain and blood pressure following TKR, suggesting that eucalyptus oil inhalation may be a nursing intervention for the relief of pain after TKR.

Activity of masticatory muscles in subjects with different orofacial pain conditions.

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Bodéré, Céline; Téa, Say Hack; Giroux-Metges, Marie Agnes; Woda, Alain

2005-07-01

The existence of a pathophysiological link between tonic muscle activity and chronic muscle pain is still being debated. The purpose of this retrospective, controlled study was to evaluate the electromyographic (EMG) activity of masticatory muscles in subjects with different orofacial pain conditions. The temporal and masseter EMG activity at rest and the masseteric reflex were recorded in two groups of patients with either myofascial pain (n=33) or neuropathic pain (n=20), one group of non-pain patients with disc derangement disorders (n=27) and one control group of healthy, asymptomatic subjects (n=32). The EMG activities of both muscles at rest were significantly higher in the pain patient groups compared to the asymptomatic control group. There was no significant difference between the disc derangement disorder group and the control group. The masseteric reflex amplitude was reduced in all patient groups when compared with the control group. In pain patient groups, the increased EMG activity at rest and the reduction of the masseteric reflex amplitude were equally distributed in the pain and non-pain sides. In addition, subjects presenting with bilateral pain showed higher EMG activity at rest than those with unilateral pain. These results suggested that the modulation of muscle activity was not the direct consequence of a peripheral nociceptive mechanism and seemed to indicate that a central mechanism was at work. The contrast between the increased EMG activity at rest and the reduction of the masseteric reflex amplitude may reflect modulations of motoneurones that differed in tonic versus phasic conditions in chronic pain patients.

Electroacupuncture Alleviates Pain Responses and Inflammation in a Rat Model of Acute Gout Arthritis

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Wenxin Chai

2018-01-01

Full Text Available Acute gout arthritis is one of the most painful inflammatory conditions. Treatments for gout pain are limited to colchicine, nonsteroidal anti-inflammatory drugs, and corticosteroids, which oftentimes result in severe adverse effects. Electroacupuncture (EA has been proved to be effective in relieving many inflammatory pain conditions with few side effects. Here, we aim to investigate the therapeutic potentials of EA on pain and inflammation of a rat model of acute gout arthritis and underlying mechanisms. We found that 2/100 Hz EA produced the most robust analgesic effect on mechanical hyperalgesia of acute gout arthritis rat model compared with 2 and 100 Hz. EA produced similar analgesic effect compared with indomethacin. 2/100 Hz EA also significantly alleviates the ongoing pain behavior, thermal hyperalgesia, and ankle edema. Locally applied μ and κ-opioid receptor antagonists but not adenosine A1 receptor antagonist significantly abolished the analgesic effect of EA. Locally applied μ and κ-opioid receptor agonists produced significant antiallodynia on acute gout arthritis rats, mimicking EA. Furthermore, 2/100 Hz EA upregulated β-endorphin expression in inflamed ankle skin tissue. Our results demonstrated, for the first time, that EA can be used for relieving acute gout arthritis with effect dependent on peripheral opioid system and comparable with the one obtained with indomethacin.

Metabotropic glutamate receptor 5 contributes to inflammatory tongue pain via extracellular signal-regulated kinase signaling in the trigeminal spinal subnucleus caudalis and upper cervical spinal cord

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Liu Ming-Gang

2012-11-01

Full Text Available Abstract Background In the orofacial region, limited information is available concerning pathological tongue pain, such as inflammatory pain or neuropathic pain occurring in the tongue. Here, we tried for the first time to establish a novel animal model of inflammatory tongue pain in rats and to investigate the roles of metabotropic glutamate receptor 5 (mGluR5-extracellular signal-regulated kinase (ERK signaling in this process. Methods Complete Freund’s adjuvant (CFA was submucosally injected into the tongue to induce the inflammatory pain phenotype that was confirmed by behavioral testing. Expression of phosphorylated ERK (pERK and mGluR5 in the trigeminal subnucleus caudalis (Vc and upper cervical spinal cord (C1-C2 were detected with immunohistochemical staining and Western blotting. pERK inhibitor, a selective mGluR5 antagonist or agonist was continuously administered for 7 days via an intrathecal (i.t. route. Local inflammatory responses were verified by tongue histology. Results Submucosal injection of CFA into the tongue produced a long-lasting mechanical allodynia and heat hyperalgesia at the inflamed site, concomitant with an increase in the pERK immunoreactivity in the Vc and C1-C2. The distribution of pERK-IR cells was laminar specific, ipsilaterally dominant, somatotopically relevant, and rostrocaudally restricted. Western blot analysis also showed an enhanced activation of ERK in the Vc and C1-C2 following CFA injection. Continuous i.t. administration of the pERK inhibitor and a selective mGluR5 antagonist significantly depressed the mechanical allodynia and heat hyperalgesia in the CFA-injected tongue. In addition, the number of pERK-IR cells in ipsilateral Vc and C1-C2 was also decreased by both drugs. Moreover, continuous i.t. administration of a selective mGluR5 agonist induced mechanical allodynia in naive rats. Conclusions The present study constructed a new animal model of inflammatory tongue pain in rodents, and

Sleep Deprivation and Recovery Sleep Prior to a Noxious Inflammatory Insult Influence Characteristics and Duration of Pain.

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Vanini, Giancarlo

2016-01-01

Insufficient sleep and chronic pain are public health epidemics. Sleep loss worsens pain and predicts the development of chronic pain. Whether previous, acute sleep loss and recovery sleep determine pain levels and duration remains poorly understood. This study tested whether acute sleep deprivation and recovery sleep prior to formalin injection alter post-injection pain levels and duration. Male Sprague-Dawley rats (n = 48) underwent sleep deprivation or ad libitum sleep for 9 hours. Thereafter, rats received a subcutaneous injection of formalin or saline into a hind paw. In the recovery sleep group, rats were allowed 24 h between sleep deprivation and the injection of formalin. Mechanical and thermal nociception were assessed using the von Frey test and Hargreaves' method. Nociceptive measures were performed at 1, 3, 7, 10, 14, 17 and 21 days post-injection. Formalin caused bilateral mechanical hypersensitivity (allodynia) that persisted for up to 21 days post-injection. Sleep deprivation significantly enhanced bilateral allodynia. There was a synergistic interaction when sleep deprivation preceded a formalin injection. Rats allowed a recovery sleep period prior to formalin injection developed allodynia only in the injected limb, with higher mechanical thresholds (less allodynia) and a shorter recovery period. There were no persistent changes in thermal nociception. The data suggest that acute sleep loss preceding an inflammatory insult enhances pain and can contribute to chronic pain. The results encourage studies in a model of surgical pain to test whether enhancing sleep reduces pain levels and duration. © 2016 Associated Professional Sleep Societies, LLC.

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.

Evaluation of reward from pain relief

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Navratilova, Edita; Xie, Jennifer Yanhua; King, Tamara; Porreca, Frank

2014-01-01

The human experience of pain is multidimensional and comprises sensory, affective, and cognitive dimensions. Preclinical assessment of pain has been largely focused on the sensory features that contribute to nociception. The affective (aversive) qualities of pain are clinically significant but have received relatively less mechanistic investigation in preclinical models. Recently, operant behaviors such as conditioned place preference, avoidance, escape from noxious stimulus, and analgesic drug self-administration have been used in rodents to evaluate affective aspects of pain. An important advance of such operant behaviors is that these approaches may allow the detection and mechanistic investigation of spontaneous neuropathic or ongoing inflammatory/nociceptive (i.e., nonevoked) pain that is otherwise difficult to assess in nonverbal animals. Operant measures may allow the identification of mechanisms that contribute differentially to reflexive hypersensitivity or to pain affect and may inform the decision to progress novel mechanisms to clinical trials for pain therapy. Additionally, operant behaviors may allow investigation of the poorly understood mechanisms and neural circuits underlying motivational aspects of pain and the reward of pain relief. PMID:23496247

Anterior cingulate cortex is crucial for contra- but not ipsi-lateral electro-acupuncture in the formalin-induced inflammatory pain model of rats

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Xing Guo-Gang

2011-08-01

Full Text Available Abstract Acupuncture and electro-acupuncture (EA are now widely used to treat disorders like pain. We and others have shown previously that current frequency, intensity and treatment duration all significantly influence the anti-nociceptive effects of EA. There is evidence that stimulating sites also affect the antinociception, with EA applied ipsilaterally to the pain site being more effective under some pain states but contralateral EA under others. It was recently reported that local adenosine A1 receptors were responsible for ipsilateral acupuncture, but what mechanisms specifically mediate the anti-nociceptive effects of contralateral acupuncture or EA remains unclear. In the present study, we applied 100 Hz EA on the ipsi- or contra-lateral side of rats with inflammatory pain induced by intra-plantar injection of formalin, and reported distinct anti-nociceptive effects and mechanisms between them. Both ipsi- and contra-lateral EA reduced the paw lifting time in the second phase of the formalin test and attenuated formalin-induced conditioned place aversion. Contralateral EA had an additional effect of reducing paw licking time, suggesting a supraspinal mechanism. Lesions of rostral anterior cingulate cortex (ACC completely abolished the anti-nociceptive effects of contra- but not ipsi-lateral EA. These findings were not lateralized effects, since injection of formalin into the left or right hind paws produced similar results. Overall, these results demonstrated distinct anti-nociceptive effects and mechanisms between different stimulating sides and implied the necessity of finding the best stimulating protocols for different pain states.

The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

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Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

2013-04-01

The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Chronic Lateral Epicondylalgia Does Not Exhibit Mechanical Pain Modulation in Response to Noxious Conditioning Heat Stimulus.

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Lim, Edwin Choon Wyn; Sterling, Michele; Vicenzino, Bill

2017-10-01

The impaired attenuation of pain by the application of a noxious conditioning stimulus at a segmentally distinct site, known as conditioned pain modulation (CPM), has been implicated in clinical pain states. Chronic lateral epicondylalgia (LE), which is characterized by lower pressure pain thresholds (PPTs) at sites remote to the affected elbow and spinal cord hyperexcitability, is a clinical pain state that might plausibly involve less efficacious CPM. This study aimed to determine whether LE exhibits a less efficacious CPM compared with that in pain-free controls. Results: Twenty participants with LE, aged 50.7 years (SD=7.05) and who had their condition for 10.2 months (range: 2 to 80 mo), were matched by age and sex to 22 pain-free participants. All participants indicated their PPT over the lateral epicondyle(s) before and during a conditioning noxious heat stimulus that was applied over the calf. A CPM score was calculated as the difference between the PPT before and during the heat pain-conditioning stimulus expressed as a percentage of PPT before the heat pain-conditioning stimulus. The condition (LE vs. control) by side (affected vs. unaffected) analysis of variance revealed a significant condition effect (P=0.001), but not side effect (P=0.192) or side-by-condition interaction effect (P=0.951). Follow-up tests for the effect of condition revealed a mean deficit in CPM of -24.5% (95% confidence interval, -38.0 to -11.0) in LE compared with that in pain-free participants. The results that suggest an impaired ability to modulate pain might be associated with the previously observed spinal cord hyperexcitability and the mechanical hyperalgesia that characterizes LE.

Systemic Inflammatory and Th17 Immune Activation among Patients Treated for Lumbar Radiculopathy Exceeds that of Patients Treated for Persistent Postoperative Neuropathic Pain.

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Shamji, Mohammed F; Guha, Daipayan; Paul, Darcia; Shcharinsky, Alina

2017-09-01

The pathophysiology of lumbar radiculopathy includes both mechanical compression and biochemical irritation of apposed neural elements. Inflammatory and immune cytokines have been implicated, induced by systemic exposure of immune-privileged intervertebral disc tissue. Surgical intervention provides improved symptoms and quality of life, but persistent postoperative neuropathic pain (PPNP) afflicts a significant fraction of patients. To compare the inflammatory and immune phenotypes among patients undergoing structural surgery for lumbar radiculopathy and spinal cord stimulation for neuropathic pain. Consecutive patients undergoing surgical intervention for lumbar radiculopathy or neuropathic pain were studied. Demographic data included age, gender, and VAS and neuropathic pain scores. Serum was evaluated for cytokine levels (IL-6, Il-17, TNF-α) and cellular content [white blood cell (WBC)/differential, lymphocyte subtypes]. The primary analysis differentiated molecular and cellular profiles between radiculopathy and neuropathic pain patients. Subgroup analysis within the surgical radiculopathy population compared those patients achieving relief of symptoms and those with PPNP. Heightened IL-6, Il-17, and TNF-α levels were observed for the lumbar radiculopathy group compared with the neuropathic pain group. This was complemented by higher WBC count and a greater fraction of Th17 lymphocytes among radiculopathy patients. In the lumbar discectomy subgroup, pain relief was seen among patients with preoperatively elevated IL-17 levels. Those patients with PPNP refractory to surgical discectomy exhibited normal cytokine levels. Differences in Th17 immune activation are seen among radiculopathy and neuropathic pain patients. These cellular and molecular profiles may be translated into biomarkers to improve patient selection for structural spine surgery. Copyright © 2017 by the Congress of Neurological Surgeons

Pain after earthquake

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Angeletti Chiara

2012-06-01

Full Text Available Abstract Introduction On 6 April 2009, at 03:32 local time, an Mw 6.3 earthquake hit the Abruzzi region of central Italy causing widespread damage in the City of L Aquila and its nearby villages. The earthquake caused 308 casualties and over 1,500 injuries, displaced more than 25,000 people and induced significant damage to more than 10,000 buildings in the L'Aquila region. Objectives This observational retrospective study evaluated the prevalence and drug treatment of pain in the five weeks following the L'Aquila earthquake (April 6, 2009. Methods 958 triage documents were analysed for patients pain severity, pain type, and treatment efficacy. Results A third of pain patients reported pain with a prevalence of 34.6%. More than half of pain patients reported severe pain (58.8%. Analgesic agents were limited to available drugs: anti-inflammatory agents, paracetamol, and weak opioids. Reduction in verbal numerical pain scores within the first 24 hours after treatment was achieved with the medications at hand. Pain prevalence and characterization exhibited a biphasic pattern with acute pain syndromes owing to trauma occurring in the first 15 days after the earthquake; traumatic pain then decreased and re-surged at around week five, owing to rebuilding efforts. In the second through fourth week, reports of pain occurred mainly owing to relapses of chronic conditions. Conclusions This study indicates that pain is prevalent during natural disasters, may exhibit a discernible pattern over the weeks following the event, and current drug treatments in this region may be adequate for emergency situations.

The epidemiology of outpatient pain treatment in pediatrics

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Baldridge S

2018-05-01

Full Text Available Stacy Baldridge, Laura Wallace, Aditi Kadakia Purdue Pharma L.P., Stamford, CT, USA Background: There is limited real-world, population-level data on the prevalence and treatment of pain in children. An understanding of pediatric pain conditions and its management can help inform provider education, treatment guidelines, and design of pediatric pain studies. Therefore, in this study, we aimed to describe the prevalence of conditions associated with acute and chronic pain in pediatric patients and to characterize pediatric pain treatment with nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 (COX-2 inhibitors, opioids (immediate release or extended release, antidepressants, topical analgesics, anticonvulsants, and other therapies based on a large, real-world sample. Materials and methods: In this cohort study, we used administrative claims data from the Truven Health MarketScan® Research Databases, which contain data regarding demography, prescription, diagnosis, and procedure performed. Descriptive statistics were used to assess the prevalence of various conditions associated with pediatric pain and to estimate the proportion of patients who received various analgesic and nonanalgesic treatments. All analyses were stratified according to demographics. Results: This study included data on more than 30 million pediatric patients from throughout the US. Overall, among patients with commercial insurance, surgery was the most common pain-related diagnosis, followed by orthopedic conditions, malignancies, trauma, and genetic conditions. For patients with Medicaid, surgery was also the most common diagnosis, followed by traumatic injury, orthopedic conditions, malignancies, and genetic conditions. These diagnoses varied by age, with most showing higher prevalence in older children. Treatment varied substantially by condition, and many children (more than 50% for most of the conditions evaluated did not receive any prescription pain treatments

ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.

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Klyne, David M; Barbe, Mary F; van den Hoorn, Wolbert; Hodges, Paul W

2018-04-01

Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific

Conditioned pain modulation (CPM) in children and adolescents: Effects of sex and age

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Tsao, Jennie C. I.; Seidman, Laura C.; Evans, Subhadra; Lung, Kirsten C.; Zeltzer, Lonnie K.; Naliboff, Bruce D.

2013-01-01

Conditioned pain modulation (CPM) refers to the diminution of perceived pain intensity for a test stimulus following application of a conditioning stimulus to a remote area of the body, and is thought to reflect the descending inhibition of nociceptive signals. Studying CPM in children may inform interventions to enhance central pain inhibition within a developmental framework. We assessed CPM in 133 healthy children (mean age = 13 years; 52.6% girls) and tested the effects of sex and age. Participants were exposed to four trials of a pressure test stimulus before, during, and after the application of a cold water conditioning stimulus. CPM was documented by a reduction in pressure pain ratings during cold water administration. Older children (12–17 years) exhibited greater CPM than younger (8–11 years) children. No sex differences in CPM were found. Lower heart rate variability (HRV) at baseline and after pain induction was associated with less CPM controlling for child age. The findings of greater CPM in the older age cohort suggest a developmental improvement in central pain inhibitory mechanisms. The results highlight the need to examine developmental and contributory factors in central pain inhibitory mechanisms in children to guide effective, age appropriate, pain interventions. PMID:23541066

Association of chest pain and risk of cardiovascular disease with coronary atherosclerosis in patients with inflammatory joint diseases

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Silvia eRollefstad

2015-11-01

Full Text Available Objectives: The relation between chest pain and coronary atherosclerosis (CA in patients with inflammatory joint diseases (IJD has not been explored previously. Our aim was to evaluate the associations of the presence of chest pain and the predicted 10-year risk of cardiovascular disease (CVD by use of several CVD risk algorithms, with multi-detector computer tomography (MDCT coronary angiography verified CA. Methods: Detailed information concerning chest pain and CVD risk factors was obtained in 335 patients with rheumatoid arthritis (RA and ankylosing spondylitis (AS. In addition, 119 of these patients underwent MDCT coronary angiography.Results: Thirty-one percent of the patients (104/335 reported chest pain. Only 6 patients (1.8% had atypical angina pectoris (pricking pain at rest. In 69 patients without chest pain, two thirds had CA, while in those who reported chest pain (n=50, CA was present in 48.0%. In a logistic regression analysis, chest pain was not associated with CA (dependent variable (p=0.43. About 30% (Nagelkerke R2 of CA was explained by any of the CVD risk calculators: SCORE, Framingham Risk Score or Reynolds Risk Score.Conclusion: The presence of chest pain was surprisingly infrequently reported in patients with IJD who were referred for a CVD risk evaluation. However, when present, chest pain was weakly associated with CA, in contrast to the predicted CVD risk by several risk calculators which was highly associated with the presence of CA. These findings suggest that clinicians treating patients with IJD should be alert of coronary atherosclerotic disease also in absence of chest pain symptoms.

Effect of experimental stress in 2 different pain conditions affecting the facial muscles.

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Woda, Alain; L'heveder, Gildas; Ouchchane, Lemlih; Bodéré, Céline

2013-05-01

Chronic facial muscle pain is a common feature in both fibromyalgia (FM) and myofascial (MF) pain conditions. In this controlled study, a possible difference in the mode of deregulation of the physiological response to a stressing stimulus was explored by applying an acute mental stress to FM and MF patients and to controls. The effects of the stress test were observed on pain, sympathetic variables, and both tonic and reflex electromyographic activities of masseteric and temporal muscles. The statistical analyses were performed through a generalized linear model including mixed effects. Painful reaction to the stressor was stronger (P < .001) and longer (P = .011) in FM than in MF independently of a higher pain level at baseline. The stress-induced autonomic changes only seen in FM patients did not reach significance. The electromyographic responses to the stress test were strongest for controls and weakest for FM. The stress test had no effect on reflex activity (area under the curve [AUC]) or latency, although AUC was high in FM and latencies were low in both pain groups. It is suggested that FM is characterized by a lower ability to adapt to acute stress than MF. This study showed that an acute psychosocial stress triggered several changes in 2 pain conditions including an increase in pain of larger amplitude in FM than in MF pain. Similar stress-induced changes should be explored as possible mechanisms for differentiation between dysfunctional pain conditions. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation.

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Canetta, Sarah E; Luca, Edlira; Pertot, Elyse; Role, Lorna W; Talmage, David A

2011-01-01

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs). Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function.

Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation.

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Sarah E Canetta

Full Text Available Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling can acutely activate phosphatidylinositol-3-kinase (PtdIns3K signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons. Transient receptor potential vanilloid 1 (TRPV1 is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K, making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function.

Pain management in older adults.

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Tracy, Bridget; Sean Morrison, R

2013-11-01

Chronic pain is prevalent among older adults but is underrecognized and undertreated. The approach to pain assessment and management in older adults requires an understanding of the physiology of aging, validated assessment tools, and common pain presentations among older adults. To identify the overall principles of pain management in older adults with a specific focus on common painful conditions and approaches to pharmacologic treatment. We searched PubMed for common pain presentations in older adults with heart failure, end-stage renal disease, dementia, frailty, and cancer. We also reviewed guidelines for pain management. Our review encompassed 2 guidelines, 10 original studies, and 22 review articles published from 2000 to the present. This review does not discuss nonpharmacologic treatments of pain. Clinical guidelines support the use of opioids in persistent nonmalignant pain. Opioids should be used in patients with moderate or severe pain or pain not otherwise controlled but with careful attention to potential toxic effects and half-life. In addition, clinical practice guidelines recommend use of oral nonsteroidal anti-inflammatory drugs with extreme caution and for defined, limited periods. An understanding of the basics of pain pathophysiology, assessment, pharmacologic management, and a familiarity with common pain presentations will allow clinicians to effectively manage pain for older adults. © 2013 Elsevier HS Journals, 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.

Pain and microcrystalline arthritis

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R. Ramonda

2014-06-01

Full Text Available Microcrystals are responsible for some of the most common and complex arthropathies which are often accompanied by intense, severe pain and inflammatory reactions. The main pathogens are crystals of monosodium urate (MSU, responsible for the gout, calcium pyrophosphate (CPP, which deposits also in various clinical forms of arthopathies, and basic calcium phosphate associated with osteoarthritis. In this context, the microcrystal arthritis is characterized by multiple, acute attacks followed by chronic pain, disability, impaired quality of life, and increased mortality. Given their chronic nature, they represent an ever more urgent public health problem. MSU and CPP crystals are also able to activate nociceptors. The pain in mycrocrystalline arthritis (MCA is an expression of the inflammatory process. In the course of these diseases there is an abundant release of inflammatory molecules, including prostaglandins 2 and kinins. Interleukin-1 represents the most important cytokine released during the crystal-induced inflammatory process. Therefore, clinically, pain is the most important component of MCA, which lead to functional impairment and disability in a large proportion of the population. It is fundamental to diagnose these diseases as early as possible, and to this aim, to identify appropriate and specific targets for a timely therapeutic intervention.

Osteoarthritis guidelines: a progressive role for topical nonsteroidal anti-inflammatory drugs

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Stanos SP

2013-04-01

Full Text Available Steven P Stanos Rehabilitation Institute of Chicago, Center for Pain Management, Chicago, IL, USA Abstract: Current treatment guidelines for the treatment of chronic pain associated with osteoarthritis reflect the collective clinical knowledge of international experts in weighing the benefits of pharmacologic therapy options while striving to minimize the negative effects associated with them. Consideration of disease progression, pattern of flares, level of functional impairment or disability, response to treatment, coexisting conditions such as cardiovascular disease or gastrointestinal disorders, and concomitant prescription medication use should be considered when creating a therapeutic plan for a patient with osteoarthritis. Although topical nonsteroidal anti-inflammatory drugs historically have not been prevalent in many of the guidelines for osteoarthritis treatment, recent evidence-based medicine and new guidelines now support their use as a viable option for the clinician seeking alternatives to typical oral formulations. This article provides a qualitative review of these treatment guidelines and the emerging role of topical nonsteroidal anti-inflammatory drugs as a therapy option for patients with localized symptoms of osteoarthritis who may be at risk for oral nonsteroidal anti-inflammatory drug-related serious adverse events. Keywords: osteoarthritis, nonsteroidal anti-inflammatory drugs, guidelines, topical analgesics, diclofenac

Neurovascular Unit in Chronic Pain

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Beatrice Mihaela Radu

2013-01-01

Full Text Available Chronic pain is a debilitating condition with major socioeconomic impact, whose neurobiological basis is still not clear. An involvement of the neurovascular unit (NVU has been recently proposed. In particular, the blood-brain barrier (BBB and blood-spinal cord barrier (BSCB, two NVU key players, may be affected during the development of chronic pain; in particular, transient permeabilization of the barrier is suggested by several inflammatory- and nerve-injury-based pain models, and we argue that the clarification of molecular BBB/BSCB permeabilization events will shed new light in understanding chronic pain mechanisms. Possible biases in experiments supporting this theory and its translational potentials are discussed. Moving beyond an exclusive focus on the role of the endothelium, we propose that our understanding of the mechanisms subserving chronic pain will benefit from the extension of research efforts to the NVU as a whole. In this view, the available evidence on the interaction between analgesic drugs and the NVU is here reviewed. Chronic pain comorbidities, such as neuroinflammatory and neurodegenerative diseases, are also discussed in view of NVU changes, together with innovative pharmacological solutions targeting NVU components in chronic pain treatment.

Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

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Deise Prehs Montrucchio

Full Text Available S-(+-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+-dicentrine (100 mg/kg reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C. Moreover, S-(+-dicentrine (100 mg/kg, p.o. was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+-dicentrine reduced the licking time (spontaneous nociception and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity, both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.

Analgesic and anti-inflammatory effects of Cyphostemma vogelii (Hook

African Journals Online (AJOL)

Rita

2013-04-24

Apr 24, 2013 ... Key words: Analgesic, anti-inflammatory, mice, Cyphostemma vogelii, nociception. ... steroidal anti- inflammatory drugs (NSAIDs) are considered the drugs of ..... 44-55. Hughes H, Lang M (1983). Control of pain in dogs and cats In: Kitchell. R, Erickson H (eds.) Animal pain. Baltimore Waverly press. pp. 207-.

Lean mass predicts conditioned pain modulation in adolescents across weight status.

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Stolzman, S; Hoeger Bement, M

2016-07-01

There is a wide continuum of conditioned pain modulation (CPM) in adults with older adults experiencing an attenuated CPM response compared with younger adults. Less is known for adolescents and the role of anthropometrics. Fifty-six adolescents (15.1 ± 1.8 years; 32 normal weight and 24 overweight/obese; 27 boys) completed in a CPM session that included anthropometric testing. Pressure pain thresholds were measured at the nailbed and deltoid muscle (test stimuli) with the foot submerged in a cool or ice water bath (conditioning stimulus). Weight status, body composition (Dual-energy X-ray absorptiometry scan), physical activity levels and clinical pain were also evaluated. The CPM response in adolescents was similar across sites (nailbed vs. deltoid), weight status (normal vs. overweight/obese) and sex. CPM measured at the deltoid muscle was positively associated with left arm lean mass but not fat mass; lean mass of the arm uniquely predicted 10% of the CPM magnitude. CPM measured at the nailbed was positively correlated with physical activity levels. These results suggest that lean mass and physical activity levels may contribute to endogenous pain inhibition in adolescents across weight status. © 2016 European Pain Federation - EFIC®

Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain

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Shih Ming-Hung

2008-12-01

Full Text Available Abstract Spinal cord α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs mediate acute spinal processing of nociceptive and non-nociceptive information, but whether and how their activation contributes to the central sensitization that underlies persistent inflammatory pain are still unclear. Here, we examined the role of spinal AMPARs in the development and maintenance of complete Freund's adjuvant (CFA-induced persistent inflammatory pain. Intrathecal application of two selective non-competitive AMPAR antagonists, CFM-2 (25 and 50 μg and GYKI 52466 (50 μg, significantly attenuated mechanical and thermal hypersensitivities on the ipsilateral hind paw at 2 and 24 h post-CFA injection. Neither CFM-2 nor GYKI 52466 affected the contralateral basal responses to thermal and mechanical stimuli. Locomotor activity was not altered in any of the drug-treated animals. CFA-induced inflammation did not change total expression or distribution of AMPAR subunits GluR1 and GluR2 in dorsal horn but did alter their subcellular distribution. The amount of GluR2 was markedly increased in the crude cytosolic fraction and decreased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. Conversely, the level of GluR1 was significantly decreased in the crude cytosolic fraction and increased in the crude membrane fraction from the ipsilateral L4–5 dorsal horn at 24 h (but not at 2 h post-CFA injection. These findings suggest that spinal AMPARs might participate in the central spinal mechanism of persistent inflammatory pain.

Mast cell-neural interactions contribute to pain and itch.

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Gupta, Kalpna; Harvima, Ilkka T

2018-03-01

Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions.

Science.gov (United States)

Alvarado-Vazquez, Perla Abigail; Bernal, Laura; Paige, Candler A; Grosick, Rachel L; Moracho Vilrriales, Carolina; Ferreira, David Wilson; Ulecia-Morón, Cristina; Romero-Sandoval, E Alfonso

2017-08-01

and practical approach for inflammatory conditions that could lead to persistent pain, i.e. major surgeries, burns, rheumatoid arthritis, etc. Copyright © 2017 Elsevier GmbH. All rights reserved.

Prediction of pain sensitivity in healthy volunteers

DEFF Research Database (Denmark)

Ravn, Pernille; Frederiksen, R; Skovsen, AP

2012-01-01

The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury.......The primary objective of the present study was to evaluate predictive parameters of the acute pain score during induction of an inflammatory heat injury....

[Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].

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Costantino, D; Guaraldi, C; Costantino, M; Bounous, V E

2015-10-01

Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.

Purinergic mechanosensory transduction and visceral pain

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Burnstock Geoffrey

2009-11-01

Full Text Available Abstract In this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown.

Diagnostic Accuracy of Quantitative Sensory Testing to Discriminate Inflammatory Toothache and Intraoral Neuropathic Pain.

Science.gov (United States)

Porporatti, André Luís; Costa, Yuri Martins; Stuginski-Barbosa, Juliana; Bonjardim, Leonardo Rigoldi; Duarte, Marco Antônio Hungaro; Conti, Paulo César Rodrigues

2015-10-01

A differential diagnosis between inflammatory toothache (IT) and intraoral neuropathic pain is challenging. The aim of this diagnostic study was to quantify somatosensory function of subjects with IT (acute pulpitis) and atypical odontalgia (AO, intraoral neuropathic pain) and healthy volunteers and to quantify how accurately quantitative sensory testing (QST) discriminates an IT or AO diagnosis. The sample consisted of 60 subjects equally divided (n = 20) into 3 groups: (1) IT, (2) AO, and (3) control. A sequence of 4 QST methods was performed over the dentoalveolar mucosa in the apical maxillar or mandibular area: mechanical detection threshold, pain detection threshold (PDT), dynamic mechanical allodynia, and temporal summation. One-way analysis of variance, Tukey post hoc analyses, and z score transformation were applied to the data. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of the QST methods were calculated (α = 5%). Somatosensory abnormalities were found for the AO group, which is consistent with a low detection threshold to touch and pain and the presence of mechanical allodynia. For the IT group, no somatosensory abnormality was observed when compared with the control group. The most accurate QST to discriminate the diagnostic differences between IT and healthy individuals is the PDT. The diagnostic differences between AO and healthy individuals and between IT and AO are best discriminated with the mechanical detection threshold, PDT, and dynamic mechanical allodynia. The proposed QST methods may aid in the differential diagnosis between IT and AO with strong accuracy and may be used as complementary diagnostic tests. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Role of Sigma-1 Receptor/p38 MAPK Inhibition in Acupoint Catgut Embedding-Mediated Analgesic Effects in Complete Freund's Adjuvant-Induced Inflammatory Pain.

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Du, Kairong; Wang, Xue; Chi, Laiting; Li, Wenzhi

2017-08-01

The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia. Rats were prepared with intrathecal catheter implantation. ACE was applied to bilateral "Kunlun" (BL60), "Zusanli" (ST36), and "Sanyinjiao" (SP6) acupoints in the rat model of inflammatory pain (complete Freund's adjuvant [CFA] intraplantar injection). Then, Sig-1R agonist PRE084 or saline was intrathecally given daily. The paw withdrawal thresholds and paw edema were measured before CFA injection and at 1, 3, and 5 day after CFA injection. Western bolt was used to evaluate the protein expression of spinal Sig-1R, p38MAPK, and extracellular signal-regulated kinase (ERK), and immunohistochemistry of Sig-1R was detected at 1, 3, and 5 days after CFA injection. ACE exhibited specific analgesic effects. ACE increased paw withdrawal thresholds and markedly decreased CFA-induced paw edema at 1, 3, and 5 days. ACE downregulated the protein expression of Sig-1R, which was increased significantly at 1, 3, and 5 days after CFA injection. ACE decreased the expression of p38 MAPK and ERK at 1 and 3 days but not at 5 days. However, an injection of Sig-1R agonist PRE084 markedly reversed these alterations, except ERK expression. The present study demonstrated that ACE exhibited antihyperalgesic effects via the inhibition of the Sig-1R that modulated p38 MAPK, but not ERK, expression in the CFA-induced inflammatory pain model in rats.

Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.

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Norbert Mair

2011-02-01

Full Text Available Sphingosine-1-phosphate (S1P is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P₁ receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P₁ receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P₁ receptor. Our data show that neuronally expressed S1P₁ receptors play a significant role in regulating nociceptor function and that S1P/S1P₁ signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation.

Differential diagnosis of calf pain by ultrasonography

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Luciano Augusto Botter

2008-03-01

Full Text Available This paper aims to evaluate the recent and numerous applications of ultrasonography in the differential diagnosis of conditions that affect the popliteal fossa and lower limbs, resulting in calf pain. Popliteal cysts and their ruptures, aneurysms, hematomas, cellulitis, abscesses, soft tissue tumors and other fluid collections are easily identified by this technique. Moreover, post-trauma and inflammatory conditions affecting muscles and tendons, muscle necrosis, deep venous thrombosis and superficial thrombophlebitis are very well demonstrated by the ultrasonographic screening.

Inflammatory conditions induce IRES-dependent translation of cyp24a1.

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Daniela Rübsamen

Full Text Available Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR-kinase, alternative modes of translation, such as internal ribosome entry site (IRES-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM. Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.

Evidence that dry eye is a comorbid pain condition in a U.S. veteran population

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Lee, Charity J.; Levitt, Roy C.; Felix, Elizabeth R.; Sarantopoulos, Constantine D.; Galor, Anat

2017-01-01

Abstract Introduction: Recent evidence suggests that dry eye (DE) may be comorbid with other chronic pain conditions. Objectives: To evaluate DE as a comorbid condition in the U.S. veteran population. Methods: Retrospective review of veterans seen in the Veterans Administration Healthcare System (Veteran Affairs) between January 1, 2010, and December 31, 2014. Dry eye and nonocular pain disorders were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. Dry eye was further separated into ICD-9 codes representing tear film dysfunction or ocular pain. χ2 and logistic regression analyses were used to examine frequency and risk of DE, ocular pain, and tear film dysfunction by pain disorders. Results: Of 3,265,894 veterans, 959,881 had a DE diagnosis (29.4%). Dry eye frequency increased with the number of pain conditions reported (P < 0.0005). Ocular pain was most strongly associated with headache (odds ratio [OR] 2.98; 95% confidence interval [CI] 2.95–3.01), tension headache (OR 2.64; 95% CI 2.58–2.71), migraine (OR 2.58; 95% CI 2.54–2.61), temporomandibular joint dysfunction (OR 2.39; 95% CI 2.34–2.44), pelvic pain (OR 2.30; 95% CI 2.24–2.37), central pain syndrome (OR 2.24; 95% CI 1.94–2.60), and fibromyalgia/muscle pain (OR 2.23; 95% CI 2.20–2.26), all P < 0.0005. Tear film dysfunction was most closely associated with osteoarthritis (OR 1.97; 95% CI 1.96–1.98) and postherpetic neuralgia (OR 1.95; 95% CI 1.90–2.00), both P < 0.0005. Conclusions: Dry eye, including both ocular pain and tear film dysfunction, is comorbid with pain conditions in this nationwide population, implying common mechanisms. PMID:29392243

Detection of systemic inflammation in severely impaired chronic pain patients, and effects of a CBT-ACT-based multi-modal pain rehabilitation program.

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Hysing, E-B; Smith, L; Thulin, M; Karlsten, R; Gordh, T

2017-12-29

Aims A few previous studies indicate an ongoing of low-grade systemic inflammation in chronic pain patients (CPP) [1, 2]. In the present study we investigated the plasma inflammatory profile in severely impaired chronic pain patients. In addition we studied if there were any alterations in inflammation patterns at one-year follow up, after the patients had taken part in a CBT-ACT based 4 weeks in-hospital pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well characterized chronic pain patients. Plasma from matched healthy blood donors were used as controls. At one year after the treatment program, 28 of the patients were available for follow up. Instead of only analyzing single inflammation-related substances, we used a new multiplex panel enabling the simultaneous analysis of 92 inflammation-related proteins, mainly cytokines and chemokines (Proseek Inflammation, Olink, Uppsala, Sweden). Multivariate statistics were used for analysis. Results Clear signs of increased inflammatory activity were detected in the pain patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43 of the 92 inflammatory biomarkers. The expression of 8 biomarkers were 4 times higher in patients compared to controls. Three biomarkers, CXCL5, SIRT2, AXIN1 were more than 8 times higher. The conventional marker for inflammation, CRP, did not differ. Of the 28 patients available for follow up one year after the intervention, all showed lower levels of the inflammatory biomarker initially raised. Conclusions The results indicate that CPP suffer from a low grade of chronic systemic inflammation, not detectable by CRP analysis. This may have implications for the general pain hypersensitivity, and other symptoms, often described in this group of patients. We conclude that inflammatory plasma proteins may be measureable molecular markers to distinguishes CPP from pain free controls, and that a CBT-ACT pain rehab program seem to

Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.

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Martel, Marc O; Wasan, Ajay D; Edwards, Robert R

2013-11-01

To examine the temporal stability of conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory controls, among a sample of patients with chronic pain. The study also examined the factors that might be responsible for the stability of CPM. In this test-retest study, patients underwent a series of standardized psychophysical pain-testing procedures designed to assess CPM on two separate occasions (i.e., baseline and follow up). Patients also completed self-report measures of catastrophizing (Pain Catastrophizing Scale [PCS] and negative affect [NA]). Overall, results provided evidence for the stability of CPM among patients with chronic pain. Results, however, revealed considerable sex differences in the stability of CPM. For women, results revealed a significant test-retest correlation between baseline and follow-up CPM scores. For men, however, the test-retest correlation between baseline and follow-up CPM scores was not significant. Results of a Fisher's Z-test revealed that the stability of CPM was significantly greater for women than for men. Follow-up analyses revealed that the difference between men and women in the stability of CPM could not be accounted for by any demographic (e.g., age) and/or psychological factors (PCS and NA). Our findings suggest that CPM paradigms possess sufficient reliability to be incorporated into bedside clinical evaluation of patients with chronic pain, but only among women. The lack of CPM reproducibility/stability observed among men places limits on the potential use of CPM paradigms in clinical settings for the assessment of men's endogenous pain-inhibitory function. Wiley Periodicals, Inc.

Effects of Progressive Resistance Exercise Training on Low Back Pain Conditions of Miners in Ghana

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Monday Omoniyi MOSES

2014-09-01

Conclusions: The low back pain conditions of miners were significantly improved using PRE, especially pain intensity, pain scale and pain frequency. Hence, exercise and physical activity that followed PRE training patterns should be majorly incorporated into the lifestyles of the miners.

Association of multiple chronic conditions and pain among older black and white adults with diabetes mellitus

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Tamara A. Baker

2017-10-01

Full Text Available Abstract Background Aging is often associated with the challenge of navigating daily tasks with a painful chronic medical illness. Yet, there is concern of the number of older adults impacted with more than one chronic condition. Despite the increasing number of adults diagnosed with diabetes and comorbid chronic illnesses, there remains a lack of understanding in how multiple illnesses relate to experiences of pain. To assess the association between multiple chronic conditions and pain, this study aimed to identify clusters of chronic medical conditions and their association with pain among a sample of older Black and White adults diagnosed with diabetes. Methods Two hundred and thirty-six participants responded to a series of questions assessing pain frequency and severity, as well as health and social characteristics. A factor analysis was used to categorize clusters of medical conditions, and multiple regression models were used to examine predictors of pain. Results Seven of the assessed chronic medical conditions loaded on three factors, and accounted for 57.2% of the total variance, with heart disease (factor 1 accounting for 21.9%, musculoskeletal conditions (factor 2 for another 18.4%, and factor 3 (microvascular diseases accounting for a final 16.9% of the variability among the chronic medical conditions. Covariate-adjusted models showed that fewer years of education and higher scores on the microvascular and musculoskeletal conditions factors were associated with higher pain frequency, with the musculoskeletal conditions factor being the strongest predictor. Conclusions Findings from this study compliment existent literature underscoring the prevalence and importance of comorbid diagnoses in relation to pain. Examining health-related factors beyond a single disease diagnosis also provides an opportunity to explore underlying disease co-occurrences that may persist beyond organ system classifications.

Tai Chi for Chronic Pain Conditions: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

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Kong, Ling Jun; Lauche, Romy; Klose, Petra; Bu, Jiang Hui; Yang, Xiao Cun; Guo, Chao Qing; Dobos, Gustav; Cheng, Ying Wu

2016-04-29

Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P complementary and alternative medicine for chronic pain conditions.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

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Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation

Temporal changes in cortical activation during conditioned pain modulation (CPM), a LORETA study.

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Moont, Ruth; Crispel, Yonatan; Lev, Rina; Pud, Dorit; Yarnitsky, David

2011-07-01

For most healthy subjects, both subjective pain ratings and pain-evoked potentials are attenuated under conditioned pain modulation (CPM; formerly termed diffuse noxious inhibitory controls, or DNIC). Although essentially spinal-bulbar, this inhibition is under cortical control. This is the first study to observe temporal as well as spatial changes in cortical activations under CPM. Specifically, we aimed to investigate the interplay of areas involved in the perception and processing of pain and those involved in controlling descending inhibition. We examined brief consecutive poststimulus time windows of 50 ms using a method of source-localization from pain evoked potentials, sLORETA. This enabled determination of dynamic changes in localized cortical generators evoked by phasic noxious heat stimuli to the left volar forearm in healthy young males, with and without conditioning hot-water pain to the right hand. We found a CPM effect characterized by an initial increased activation in the orbitofrontal cortex (OFC) and amygdala at 250-300 ms poststimulus, which was correlated with the extent of psychophysical pain reduction. This was followed by reduced activations in the primary and secondary somatosensory cortices, supplementary motor area, posterior insula, and anterior cingulate cortex from 400 ms poststimulus. Our findings show that the prefrontal pain-controlling areas of OFC and amygdala increase their activity in parallel with subjective pain reduction under CPM, and that this increased activity occurs prior to reductions in activations of the pain sensory areas. In conclusion, achieving pain inhibition by the CPM process seems to be under control of the OFC and the amygdala. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

A Rare Cause of Acute Abdominal Pain: Primary Appendagitis Epiploica

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Tarkan Ergun

2014-03-01

Primary appendagitis epiploica – one of the causes of acute abdominal pain – is a self-limited rare benign inflammatory condition involving the colonic epiploic appendages. Their therapy is conservative and clinically mimics other conditions requiring surgery such as acute diverticulitis or appendicitis. However, being a quite rare condition is the reason they are usually neglected by both the surgeon and the radiologist. However the computed tomography (CT findings are rather characteristic and pathognomonic. Thus, to consider CT as the diagnostic modality of choice is extremely important in order to diagnose the condition and to avoid unnecessary surgical interventions.             This is a paper reporting an acute abdominal pain case of primary appendicitis epiploica diagnosed using computed tomography. 

MicroRNA modulation in complex regional pain syndrome

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Orlova Irina A

2011-11-01

Full Text Available Abstract Background Aberrant expression of small noncoding RNAs called microRNAs (miRNAs is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. Methods We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. Results Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF, interleukin1 receptor antagonist (IL1Ra and monocyte chemotactic protein-1 (MCP1 were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

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Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

2018-05-16

Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

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Busch Melanie

2009-12-01

Full Text Available Abstract Background Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC on complete Freund's adjuvant-induced inflammatory pain in rats. Results POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin. Conclusion Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

Pain-relevant anxiety affects desire for pain relief, but not pain perception

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Adriana Banozic

2017-01-01

Full Text Available Background: Pain context plays a significant role in the perception of pain. Despite recent interest in vicarious learning and anxiety in pain modulation, there have been no attempts to explore pain modulation by specific environmental cues. Aims: Therefore, the present study evaluated pain responses in the condition that was attributed as either anxiety relevant (AR or anxiety irrelevant. Materials and Methods: Participants were exposed to both conditions through social observational learning. Pain perception was assessed by means of a visual analog scale ranging from 0 = no pain to 10 = maximum imaginable pain. State anxiety, empathy, expectancy, and desire for pain relief were also measured at both neutral and emotionally inducing conditions. Results: No effect of relevancy of anxiety for the pain context on any of the pain-related constructs was found. However, participants in the AR condition reported an increased desire for pain relief. Maximizing similarities between observed and experienced pain context did not enhance observational learning effects in the emotionally inducing condition regardless of its relevance, but significant changes were found in comparison to the affectively neutral group. Conclusions: These results could have potentially significant clinical implications suggesting that even though observing painful procedures does not increase pain it could affect medication usage.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

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Siebenhuener, Klarissa; Eschmann, Emmanuel; Kienast, Alexander; Schneider, Dominik; Minder, Christoph E.; Saller, Reinhard; Zimmerli, Lukas; Blaser, Jürg; Battegay, Edouard

2017-01-01

Background Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. Methods and Findings We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). Conclusions Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication

Hybrid protocols plus natural treatments for inflammatory conditions.

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1998-01-01

Hybrid protocols combine one, two, or three pharmaceutical drugs with several nutritional or immune-based therapies. These protocols are not limited solely to FDA-approved drugs or strictly to alternative therapies. The rationale for using a hybrid protocol is to find an effective antiviral regimen that also restores immune function. The goal is to obtain the benefits of protease inhibitors without viral resistance and side effects which include problems with fat metabolism and cholesterol levels. Natural treatments for inflammatory conditions are also described. Options include licorice root, ginger root, and slippery elm.

Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia.

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Huang, Chun-Ping; Chen, Hsiang-Ni; Su, Hong-Lin; Hsieh, Ching-Liang; Chen, Wei-Hsin; Lai, Zhen-Rung; Lin, Yi-Wen

2013-01-01

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

Reliability of conditioned pain modulation: a systematic review

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Kennedy, Donna L.; Kemp, Harriet I.; Ridout, Deborah; Yarnitsky, David; Rice, Andrew S.C.

2016-01-01

Abstract A systematic literature review was undertaken to determine if conditioned pain modulation (CPM) is reliable. Longitudinal, English language observational studies of the repeatability of a CPM test paradigm in adult humans were included. Two independent reviewers assessed the risk of bias in 6 domains; study participation; study attrition; prognostic factor measurement; outcome measurement; confounding and analysis using the Quality in Prognosis Studies (QUIPS) critical assessment tool. Intraclass correlation coefficients (ICCs) less than 0.4 were considered to be poor; 0.4 and 0.59 to be fair; 0.6 and 0.75 good and greater than 0.75 excellent. Ten studies were included in the final review. Meta-analysis was not appropriate because of differences between studies. The intersession reliability of the CPM effect was investigated in 8 studies and reported as good (ICC = 0.6-0.75) in 3 studies and excellent (ICC > 0.75) in subgroups in 2 of those 3. The assessment of risk of bias demonstrated that reporting is not comprehensive for the description of sample demographics, recruitment strategy, and study attrition. The absence of blinding, a lack of control for confounding factors, and lack of standardisation in statistical analysis are common. Conditioned pain modulation is a reliable measure; however, the degree of reliability is heavily dependent on stimulation parameters and study methodology and this warrants consideration for investigators. The validation of CPM as a robust prognostic factor in experimental and clinical pain studies may be facilitated by improvements in the reporting of CPM reliability studies. PMID:27559835

Acupuncture for chronic pain: an update and critical overview.

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Yin, Changshik; Buchheit, Thomas E; Park, Jongbae J

2017-10-01

Acupuncture is now recommended for several chronic pain conditions. Despite supportive evidence of its effectiveness, this ancient approach is often misunderstood, and may still be underused in mainstream practice. A critical review on its effectiveness and practice integration, and mechanisms of action is essential to the medical community that is continuing to seek nonopioid therapies for chronic pain. Mounting evidence supports the effectiveness of acupuncture to treat chronic low back, neck, shoulder, and knee pain, as well as headaches. Additional data are emerging that support the use of acupuncture as an adjunct or alternative to opioids, and in perioperative settings. Findings related to its mechanisms of action include transient receptor potential cation channel vanilloid 1 activation in the periphery, microglial suppression in the cerebral cortex and spinal cord, and regulation of cytokines and other key inflammatory factors in the spinal cord. Incremental integration of acupuncture into pain medicine practices and training programmes continues to grow. Acupuncture is effective, safe, and cost-effective for treating several chronic pain conditions when performed by well-trained healthcare professionals. Further studies on its use as an adjunct or alternative to opioids, and in perioperative settings are needed.

Pre-existing Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced BRONJ Lesions in Mice

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Song, Minju; Alshaikh, Abdullah; Kim, Terresa; Kim, Sol; Dang, Michelle; Mehrazarin, Shebli; Shin, Ki-Hyuk; Kang, Mo; Park, No-Hee; Kim, Reuben H.

2016-01-01

Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ. PMID:27637460

When is irritable bowel syndrome not irritable bowel syndrome? Diagnosis and treatment of chronic functional abdominal pain.

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Grover, Madhusudan

2012-08-01

Functional abdominal pain syndrome (FAPS) is a distinct chronic gastrointestinal (GI) pain disorder characterized by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods. The pain experience in FAPS is predominantly centrally driven as compared to other chronic painful GI conditions such as inflammatory bowel disease and chronic pancreatitis where peripherally acting factors play a major role in driving the pain. Psychosocial factors are often integrally associated with the disorder and can pose significant challenges to evaluation and treatment. Patients suffer from considerable loss of function, which can drive health care utilization. Treatment options are limited at best with most therapeutic regimens extrapolated from pain management of other functional GI disorders and chronic pain conditions. A comprehensive approach to management using a biopsychosocial construct and collaboration with pain specialists and psychiatry is most beneficial to the management of this disorder.

Flank pain

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... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows.

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Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R; Olsen, Jesse R; Jeffress, Erin J; Moore, Dale A; Kastelic, John P

2013-11-09

Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P cows with subclinical endometritis compared to normal cows (P insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P insulin, and IGF-1 had significant associations with BCS categories (low vs. high) and postpartum uterine inflammatory conditions. Perhaps loss of

Pain, power and patience - A narrative study of general practitioners' relations with chronic pain patients

OpenAIRE

Hemborg Kristiansson, Mia; Brorsson, Annika; Wachtler, Caroline; Troein, Margareta

2011-01-01

Abstract Background Chronic pain patients are common in general practice. In this study "chronic pain" is defined as diffuse musculoskeletal pain not due to inflammatory diseases or cancer. Effective patient-physician relations improve treatment results. The relationship between doctors and chronic pain patients is often dysfunctional. Consultation training for physicians and medical students can improve the professional ability to build effective relations, but this demands a thorough unders...

The Acquisition and Extinction of Fear of Painful Touch: a Novel Tactile Fear Conditioning Paradigm

NARCIS (Netherlands)

Biggs, Emma E; Meulders, Ann; Kaas, Amanda L; Goebel, R.; Vlaeyen, Johan W S

2017-01-01

Fear of touch, due to allodynia and spontaneous pain, is not well-understood. Experimental methods to advance this topic are lacking, and therefore we propose a novel tactile conditioning paradigm. Seventy-six pain-free participants underwent acquisition in both a predictable and unpredictable pain

Osteoarthritis: the genesis of pain.

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Fu, Kai; Robbins, Sarah R; McDougall, Jason J

2018-05-01

OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

Anti-inflammatory management for tendon injuries - friends or foes?

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Chan Kai-Ming

2009-10-01

Full Text Available Abstract Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic tendon injuries we treat as specialists have received non-steroidal anti-inflammatory drugs by their physician, suggesting that there might be a potential interaction in some of these cases turning a mild inflammatory tendon injury into chronic tendinopathy in predisposed individuals. We are aware of the fact that non-steroidal anti-inflammatory drugs and corticosteroids may well have a positive effect on the pain control in the clinical situation whilst negatively affect the structural healing. It follows that a comprehensive evaluation of anti-inflammatory management for tendon injuries is needed and any such data would have profound clinical and health economic importance.

Ketamine analgesia for inflammatory pain in neonatal rats: a factorial randomized trial examining long-term effects

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Bhutta Adnan T

2008-08-01

Full Text Available Abstract Background Neonatal rats exposed to repetitive inflammatory pain have altered behaviors in young adulthood, partly ameliorated by Ketamine analgesia. We examined the relationships between protein expression, neuronal survival and plasticity in the neonatal rat brain, and correlated these changes with adult cognitive behavior. Methods Using Western immunoblot techniques, homogenates of cortical tissue were analyzed from neonatal rats 18–20 hours following repeated exposure to 4% formalin injections (F, N = 9, Ketamine (K, 2.5 mg/kg × 2, N = 9, Ketamine prior to formalin (KF, N = 9, or undisturbed controls (C, N = 9. Brain tissues from another cohort of rat pups (F = 11, K = 12, KF = 10, C = 15 were used for cellular staining with Fos immunohistochemistry or FluoroJade-B (FJB, followed by cell counting in eleven cortical and three hippocampal areas. Long-term cognitive testing using a delayed non-match to sample (DNMS paradigm in the 8-arm radial maze was performed in adult rats receiving the same treatments (F = 20, K = 24, KF = 21, C = 27 in the neonatal period. Results Greater cell death occurred in F vs. C, K, KF in parietal and retrosplenial areas, vs. K, KF in piriform, temporal, and occipital areas, vs. C, K in frontal and hindlimb areas. In retrosplenial cortex, less Fos expression occurred in F vs. C, KF. Cell death correlated inversely with Fos expression in piriform, retrosplenial, and occipital areas, but only in F. Cortical expression of glial fibrillary acidic protein (GFAP was elevated in F, K and KF vs. C. No significant differences occurred in Caspase-3, Bax, and Bcl-2 expression between groups, but cellular changes in cortical areas were significantly correlated with protein expression patterns. Cluster analysis of the frequencies and durations of behaviors grouped them as exploratory, learning, preparatory, consumptive, and foraging behaviors. Neonatal inflammatory pain exposure reduced exploratory behaviors in adult

Analgesic, anti-inflammatory and anti-platelet activities of Buddleja crispa.

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Bukhari, Ishfaq A; Gilani, Anwar H; Meo, Sultan Ayoub; Saeed, Anjum

2016-02-25

Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa. Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests. The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml. The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

Localized scleroderma and regional inflammatory myopathy.

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Zivković, Saša A; Freiberg, William; Lacomis, David; Domsic, Robyn T; Medsger, Thomas A

2014-05-01

Inflammatory myopathy is rare in localized scleroderma. We report 2 new cases of regional inflammatory myopathy associated with localized scleroderma and review 10 reported cases of localized scleroderma associated with an inflammatory myopathy with regional muscle involvement, more often in the upper extremities. Serum creatine kinase was mildly elevated or normal. Histopathology often showed perimysial inflammation and plasma cell infiltration. These cases demonstrate that inflammatory myopathy should be considered in patients with localized scleroderma and regional muscle weakness, pain or atrophy. Muscle biopsy can confirm the diagnosis of myositis, which if identified, will require anti-inflammatory and/or immunosuppressive therapy. Published by Elsevier B.V.

Cannabis use amongst patients with inflammatory bowel disease.

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Lal, Simon; Prasad, Neeraj; Ryan, Manijeh; Tangri, Sabrena; Silverberg, Mark S; Gordon, Allan; Steinhart, Hillary

2011-10-01

Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn's disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); Pmedicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); Pcannabis for IBD. Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.

Does transcutaneous electrical nerve stimulation (TENS have a clinically relevant analgesic effect on different pain conditions? A literature review

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Asami Naka

2013-07-01

Full Text Available Transcutaneous electric nerve stimulation (TENS is a standard therapy used in different painful conditions such as low back pain, diabetic polyneuropathy or arthrosis. However, literature reviews focusing on the effects and the clinical implication of this method in various painful conditions are yet scarce. The purpose of this literature research was to determine, whether TENS provides an analgesic effect on common painful conditions in clinical practice. Literature research was performed using three data bases (Pubmed, Embase, Cochrane Database, focusing on papers published in the space of time from 2007 to 2012. Papers were evaluated from two reviewers independently concerning the clinical outcome, taking account for the level of external evidence according to the German Cochrane levels of evidence (Ia – IV. 133 papers of varying methodological quality dealing with different painful conditions were selected in total. A clinically relevant analgesic effect was described in 90 painful conditions (67%. In 30 painful states (22%, the outcome was inconclusive due to the study design. No significant analgesic effect of TENS was observed in 15 painful conditions (11%. The vast majority of the papers were classified as Cochrane evidence level Ib (n = 64; 48%, followed by level Ia (n = 23; 17%, level III (n = 18; 14%, level IV (n = 15; 11%, level IIb (n = 10; 8% and level IIa (n = 3; 2%. Most of the studies revealed an analgesic effect in various painful conditions, confirming the usefulness of TENS in clinical practice.

Pain – Part I. Pharmaco-therapeutic management (ro.

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Tuns, C. I.,

2011-12-01

Full Text Available The complexity of pain mechanisms require different treatments that address to the different stages of pain production, transmission, modulation and control and at the same time can be individualized according to each patient. In this respect several substances with specific anti-inflammatory, analgesic, antipyretic activity,tranquilizers, etc. are successfully used in pain, they are supplemented by physical and chemical means. Treatment of pain is achieved by removing the cause that produced it. Elimination of inflammation, ischemia control, of infection or nerve compression, many times can lead to complete disappearance of pain. In thepresent referate groups of substances with implications in pain are presented. Are presented sintheticaly:amines, antihistamines group, anti-inflammatory nonsteroidic drugs (classic and modern, anesthetics and tranquilizers groups etc. Are also presented other means of pain therapy (analgesic electrotherapy: low frequency effect analgesic currents: diadynamic, Trabert, stochastic, transcutaneous electrical nerve stimulation (TENS, pain stimulation by galvanic current.

Towards an ICF Core Set for chronic musculoskeletal conditions: commonalities across ICF Core Sets for osteoarthritis, rheumatoid arthritis, osteoporosis, low back pain and chronic widespread pain.

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Schwarzkopf, S R; Ewert, T; Dreinhöfer, K E; Cieza, A; Stucki, G

2008-11-01

The objective of the study was to identify commonalities among the International Classification of Functioning, Disability and Health (ICF) Core Sets of osteoarthritis (OA), osteoporosis (OP), low back pain (LBP), rheumatoid arthritis (RA) and chronic widespread pain (CWP). The aim is to identify relevant categories for the development of a tentative ICF Core Set for musculoskeletal and pain conditions. The ICF categories common to the five musculoskeletal and pain conditions in the Brief and Comprehensive ICF Core Sets were identified in three steps. In a first step, the commonalities across the Brief and Comprehensive ICF Core Sets for these conditions were examined. In a second and third step, we analysed the increase in commonalities when iteratively excluding one or two of the five conditions. In the first step, 29 common categories out of the total number of 120 categories were identified across the Comprehensive ICF Core Sets of all musculoskeletal and pain conditions, primarily in the component activities and participation. In the second and third step, we found that the exclusion of CWP across the Comprehensive ICF Core Sets increased the commonalities of the remaining four musculoskeletal conditions in a maximum of ten additional categories. The Brief ICF Core Sets of all musculoskeletal and pain conditions contain four common categories out of a total number of 62 categories. The iterative exclusion of a singular condition did not significantly increase the commonalities in the remaining. Based on our analysis, it seems possible to develop a tentative Comprehensive ICF Core Set across a number of musculoskeletal conditions including LBP, OA, OP and RA. However, the profile of functioning in people with CWP differs considerably and should not be further considered for a common ICF Core Set.

A case of unilateral atypical orofacial pain with Eagle's syndrome

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G V Sowmya

2016-01-01

Full Text Available Eagle's syndrome is not an uncommon condition, but less known to physicians, where an elongated styloid process or calcified stylohyoid ligament compresses the adjacent anatomical structures leading to orofacial pain. Diagnosis is made with appropriate radiological examination. Nonsurgical treatment options include reassurance, analgesia, and anti.inflammatory medications; and the surgical option includes a transoral or external approach. Here, we present a case report of a male patient, of age38 years, with a chief complaint of unilateral atypical orofacial pain on the right side of his face radiating to the neck region, for the last two months.

VGLUTs and Glutamate Synthesis—Focus on DRG Neurons and Pain

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Mariana Malet

2015-12-01

Full Text Available The amino acid glutamate is the principal excitatory transmitter in the nervous system, including in sensory neurons that convey pain sensation from the periphery to the brain. It is now well established that a family of membrane proteins, termed vesicular glutamate transporters (VGLUTs, serve a critical function in these neurons: they incorporate glutamate into synaptic vesicles. VGLUTs have a central role both under normal neurotransmission and pathological conditions, such as neuropathic or inflammatory pain. In the present short review, we will address VGLUTs in the context of primary afferent neurons. We will focus on the role of VGLUTs in pain triggered by noxious stimuli, peripheral nerve injury, and tissue inflammation, as mostly explored in transgenic mice. The possible interplay between glutamate biosynthesis and VGLUT-dependent packaging in synaptic vesicles, and its potential impact in various pain states will be presented.

Controlling pain during orthodontic fixed appliance therapy with non-steroidal anti-inflammatory drugs (NSAID): a randomized, double-blinded, placebo-controlled study.

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Gupta, Mudit; Kandula, Srinivas; Laxmikanth, Sarala M; Vyavahare, Shreyas S; Reddy, Satheesha B H; Ramachandra, Chanila S

2014-11-01

Despite all the technological advances in orthodontics, orthodontic treatment still seems to involve some degree of discomfort and/or pain. Pain control during orthodontic therapy is of great concern to both orthodontists and patients. However, there has been limited research into controlling such pain. The purpose of this work was to assess patient-perceived pain following fixed orthodontic treatment and to evaluate the comparative analgesic efficacy of non-steroidal anti-inflammatory drugs for controlling pain. A total of 45 patients about to undergo fixed appliance orthodontic treatment were enrolled in this double-blind prospective study. Patients were evenly and randomly distributed in a blinded manner to one of three groups as follows: paracetamol/acetaminophen 500 mg thrice daily; placebo in the form of empty capsules; and etoricoxib 60 mg once daily. Drug administration began 1 h before initiating the bonding procedure and archwire placement, and given until the day 3. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 h after insertion of the appliance; 6 h thereafter and again at nighttime of the same day of the appointment; 24 h later and on the 2nd day at nighttime; 48 h after the appointment and on day 3 at nighttime. Our results revealed that moderately intense pain is associated with routine orthodontic treatment, and that the amount of pain individuals perceive varies widely. We observed statistically significant differences in the pain control among the three groups, and that etoricoxib 60 mg proved most efficient. Etoricoxib 60 mg is highly efficacious for controlling pain during fixed orthodontic appliance therapy.

Responses to tonic heat pain in the ongoing EEG under conditions of controlled attention.

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Giehl, Janet; Meyer-Brandis, Gesa; Kunz, Miriam; Lautenbacher, Stefan

2014-03-01

To confirm the existence of an ongoing electroencephalogram (EEG) pattern that is truly suggestive of pain, tonic heat pain was induced by small heat pulses at 1 °C above the pain threshold and compared to slightly less intense tonic non-painful heat pulses at 1 °C below the pain threshold. Twenty healthy subjects rated the sensation intensity during thermal stimulation. Possible confounding effects of attention were thoroughly controlled for by testing in four conditions: (1) focus of attention directed ipsilateral or (2) contralateral to the side of the stimulation, (3) control without a side preference, and (4) no control of attention at all. EEG was recorded via eight leads according to the 10/20 convention. Absolute power was computed for the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha1 (8-11 Hz), alpha2 (11-14 Hz), beta1 (14-25 Hz), and beta2 (25-35 Hz). Ratings were clearly distinct between the heat and pain conditions and suggestive for heat and pain sensations. Manipulation of attention proved to be successful by producing effects on the ratings and on the EEG activity (with lower ratings and lower EEG activity (theta, beta1, 2) over central areas for side-focused attention). During pain stimulation, lower central alpha1 and alpha2 activity and higher right-parietal and right-occipital delta power were observed compared to heat stimulation. This EEG pattern was not influenced by the manipulation of attention. Since the two types of stimuli (pain, heat) were subjectively felt differently although stimulation intensities were nearby, we conclude that this EEG pattern is clearly suggestive of pain.

Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects.

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Wehling, Martin

2014-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, and this widespread use is complicated by safety issues. A Literature review was conducted. NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. Most adverse effects are related to generalized inhibition of the major targets of NSAIDs: cyclooxygenases I and II. These enzymes are not only involved in pain and inflammation pathogenesis but are also required in the gastrointestinal (GI) tract for mucosal protection and gut motility, and in the kidneys for functional integrity. Thus, the mechanisms of NSAID toxicity are well understood, but the consequences are largely uncontrolled in clinical practice. GI ulcers, including bleeding ulcers, may occur in several percent of all chronic unprotected, high-dose NSAID users. Renal side effects may precipitate renal failure, resulting in acute dialysis and chronic retention. This includes sodium retention, resulting in arterial hypertension, heart failure, and atherosclerotic events. Cardiovascular risk may be tripled by chronic high-dose NSAID use in long-term clinical trials though "real-life studies" indicate lower risk ratios. Off-target side effects include allergic reactions, drug-induced liver injury, and central nervous system effects. Management of pain and inflammation must consider those risks and find alternative drugs or approaches to limit the negative impact of NSAIDs on mortality and morbidity. Alternative drugs, low-dose/short-term use, but especially non-pharmacologic approaches, such as physiotherapy, exercise, neurophysiologic measures, and local therapies, need to be further utilized. The appalling equation "less pain-more deaths/morbidity" ultimately necessitates treatment optimization in the individual patient.

Effects of Preoperative Non-Steroidal Anti-Inflammatory Drugs on Pain Mitigation and Patients’ Shoulder Performance Following Rotator Cuff Repair

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Alireza Rouhani

2014-12-01

Full Text Available Purpose: Pain is one of the most important factors adversely affecting clinical outcomes of operated patients. The present study aims at evaluating effects of preoperative COX2 non-steroidal anti-inflammatory inhibitors on pain mitigation and performance of patients with shoulder rotator cuff tear. Methods: This case-control study was conducted on 60 patients suffering from rotator cuff injury candidate for arthroscopic repair. The patients were classified in two parallel and matched groups. One group (case group was treated using Celecoxib (200mg/12h started 48 hours before surgery and continued for 10 days after operation. In the control group, the placebo was prescribed in the same way. Postoperative pain, side effects, sleep disturbance, and short-term outcomes were compared between two groups using DASH questionnaire. Results: Postoperative pain in the Celecoxib group significantly decreased in comparison with the control one. The difference was statistically meaningful (P<0.001. Well motion ability was seen in 80% of patients of the Celecoxib group. It was 26.6% in the placebo group since pain inhibited them from exercising more motions. In this regard, there was a statistically meaningful difference between these two groups (P=0.02. Sleep disturbance was meaningfully at higher levels in the placebo group (P=0.001. Following up the patients for three months, it was made clear that performance of the Celecoxib group was better than that of the placebo one. Conclusion: COX2 inhibitors are well efficient in patients’ pain management after arthroscopic rotator cuff repair surgery. It results in less life complications, less sleep disturbances, improvement of patients’ short-term clinical outcome, and more quick recovery.

Endogenous Opioid-Masked Latent Pain Sensitization

DEFF Research Database (Denmark)

Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

2015-01-01

UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chr...

New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS).

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Sieper, J; van der Heijde, D; Landewé, R; Brandt, J; Burgos-Vagas, R; Collantes-Estevez, E; Dijkmans, B; Dougados, M; Khan, M A; Leirisalo-Repo, M; van der Linden, S; Maksymowych, W P; Mielants, H; Olivieri, I; Rudwaleit, M

2009-06-01

Inflammatory back pain (IBP) is an important clinical symptom in patients with axial spondyloarthritis (SpA), and relevant for classification and diagnosis. In the present report, a new approach for the development of IBP classification criteria is discussed. Rheumatologists (n = 13) who are experts in SpA took part in a 2-day international workshop to investigate 20 patients with back pain and possible SpA. Each expert documented the presence/absence of clinical parameters typical for IBP, and judged whether IBP was considered present or absent based on the received information. This expert judgement was used as the dependent variable in a logistic regression analysis in order to identify those individual IBP parameters that contributed best to a diagnosis of IBP. The new set of IBP criteria was validated in a separate cohort of patients (n = 648). Five parameters best explained IBP according to the experts. These were: (1) improvement with exercise (odds ratio (OR) 23.1); (2) pain at night (OR 20.4); (3) insidious onset (OR 12.7); (4) age at onset validation cohort. This new approach with real patients defines a set of IBP definition criteria using overall expert judgement on IBP as the gold standard. The IBP experts' criteria are robust, easy to apply and have good face validity.

Balneotherapy in elderly patients: effect on pain from degenerative knee and spine conditions and on quality of life.

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Gaál, János; Varga, József; Szekanecz, Zoltán; Kurkó, Julia; Ficzere, Andrea; Bodolay, Edit; Bender, Tamás

2008-05-01

Balneotherapy is an established treatment modality for musculoskeletal disease, but few studies have examined the efficacy of spa therapy in elderly patients with degenerative spine and joint diseases. To assess the effects of balneotherapy on chronic musculoskeletal pain, functional capacity, and quality of life in elderly patients with osteoarthritis of the knee or with chronic low back pain. The 81 patients in the study group underwent a 1 day course of 30 minute daily baths in mineral water. Changes were evaluated in the following parameters: pain intensity, functional capacity, quality of life, use of non-steroidal anti-inflammatory or analgesic drugs, subjective disease severity perceived by the patients, investigator-rated disease severity, and severity of pain perceived by the patients. We analyzed the results of 76 subjects as 5 did not complete the study. Compared to baseline, all monitored parameters were significantly improved by balneotherapy in both investigated groups. Moreover, the favorable effect was prolonged for 3 months after treatment. This study showed that balneotherapy is an effective treatment modality in elderly patients with osteoarthritis of the knee or with chronic low back pain, and its benefits last for at least 3 months after treatment.

Activated microglia in the spinal cord underlies diabetic neuropathic pain.

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Wang, Dongmei; Couture, Réjean; Hong, Yanguo

2014-04-05

Diabetes mellitus is an increasingly common chronic medical condition. Approximately 30% of diabetic patients develop neuropathic pain, manifested as spontaneous pain, hyperalgesia and allodynia. Hyperglycemia induces metabolic changes in peripheral tissues and enhances oxidative stress in nerve fibers. The damages and subsequent reactive inflammation affect structural properties of Schwann cells and axons leading to the release of neuropoietic mediators, such as pro-inflammatory cytokines and pro-nociceptive mediators. Therefore, diabetic neuropathic pain (DNP) shares some histological features and underlying mechanisms with traumatic neuropathy. DNP displays, however, other distinct features; for instance, sensory input to the spinal cord decreases rather than increasing in diabetic patients. Consequently, development of central sensitization in DNP involves mechanisms that are distinct from traumatic neuropathic pain. In DNP, the contribution of spinal cord microglia activation to central sensitization and pain processes is emerging as a new concept. Besides inflammation in the periphery, hyperglycemia and the resulting production of reactive oxygen species affect the local microenvironment in the spinal cord. All these alterations could trigger resting and sessile microglia to the activated phenotype. In turn, microglia synthesize and release pro-inflammatory cytokines and neuroactive molecules capable of inducing hyperactivity of spinal nociceptive neurons. Hence, it is imperative to elucidate glial mechanisms underlying DNP for the development of effective therapeutic agents. The present review highlights the recent developments regarding the contribution of spinal microglia as compelling target for the treatment of DNP. Copyright © 2014 Elsevier B.V. All rights reserved.

Overlap between functional abdominal pain disorders and organic diseases in children.

Science.gov (United States)

Langshaw, A H; Rosen, J M; Pensabene, L; Borrelli, O; Salvatore, S; Thapar, N; Concolino, D; Saps, M

2018-04-02

Functional abdominal pain disorders are highly prevalent in children. These disorders can be present in isolation or combined with organic diseases, such as celiac disease and inflammatory bowel diseases. Intestinal inflammation (infectious and non-infectious) predisposes children to the development of visceral hypersensitivity that can manifest as functional abdominal pain disorders, including irritable bowel syndrome. The new onset of irritable bowel syndrome symptoms in a patient with an underlying organic disease, such as inflammatory bowel disease, is clinically challenging, given that the same symptomatology may represent a flare-up of the inflammatory bowel disease or an overlapping functional abdominal pain disorder. Similarly, irritable bowel syndrome symptoms in a child previously diagnosed with celiac disease may occur due to poorly controlled celiac disease or the overlap with a functional abdominal pain disorder. There is little research on the overlap of functional abdominal disorders with organic diseases in children. Studies suggest that the overlap between functional abdominal pain disorders and inflammatory bowel disease is more common in adults than in children. The causes for these differences in prevalence are unknown. Only a handful of studies have been published on the overlap between celiac disease and functional abdominal pain disorders in children. The present article provides a review of the literature on the overlap between celiac disease, inflammatory bowel disease, and functional abdominal pain disorders in children and establish comparisons with studies conducted on adults. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

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...

The protective effect of bee venom on fibrosis causing inflammatory diseases.

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Lee, Woo-Ram; Pak, Sok Cheon; Park, Kwan-Kyu

2015-11-16

Bee venom therapy is a treatment modality that may be thousands of years old and involves the application of live bee stings to the patient's skin or, in more recent years, the injection of bee venom into the skin with a hypodermic needle. Studies have proven the effectiveness of bee venom in treating pathological conditions such as arthritis, pain and cancerous tumors. However, there has not been sufficient review to fully elucidate the cellular mechanisms of the anti-inflammatory effects of bee venom and its components. In this respect, the present study reviews current understanding of the mechanisms of the anti-inflammatory properties of bee venom and its components in the treatment of liver fibrosis, atherosclerosis and skin disease.

[Complex regional pain syndrome (CRPS) : An update].

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Dimova, V; Birklein, F

2018-04-17

The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists. A stage adapted, targeted treatment could improve the prognosis. Effective multidisciplinary treatment includes the following: pharmacotherapy with steroids, bisphosphonates, or dimethylsulfoxide cream (acute phase), and antineuropathic analgesics (all phases); physiotherapy and behavioral therapy for pain-related anxiety and avoidance of movement; and interventional treatment like spinal cord or dorsal root ganglion stimulation if noninvasive options failed.

Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation.

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Hannibal, Kara E; Bishop, Mark D

2014-12-01

Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to

Inflammatory spine disease as a cause of back pain; Entzuendliche Wirbelsaeulenerkrankungen als Ursache fuer Rueckenschmerzen

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Schlossbauer, T.; Panteleon, A.; Becker-Gaab, C. [Klinikum Innenstadt der Ludwig-Maximilians-Universitaet, Institut fuer Klinische Radiologe, Muenchen (Germany)

2006-06-15

The aim of this review is to evaluate the role of inflammatory spine disease in patients with chronic back pain. The contribution of imaging modalities for the diagnostic evaluation of back pain is discussed. A systematic literature search based on the classification of seronegative spondyloarthropathies and rheumatoid arthritis was performed. The results of this search and the experiences in a large collective of rheumatological patients are analyzed. The prevalence of rheumatoid arthritis (1-2%) is comparable to that of spondyloarthropathies (1.9%). The etiology of these entities is not fully elucidated. Magnetic resonance imaging is increasingly used for early detection and surveillance of therapy with TNF-{alpha} antagonists. Bone marrow edema, which is only detectable with MRI, represents an early sign of inflammation. Therapy with TNF-{alpha} antagonists is based on clinical and laboratory criteria, and signs of inflammation in MRI. MRI is useful for assessment of the effectiveness of anti-inflammatory therapy. (orig.) [German] Ziel der Arbeit ist, die Bedeutung inflammatorischer Wirbelsaeulenerkrankungen fuer das Leitsymptom Rueckenschmerz zu eroertern. Die Aussagekraft der verschiedenen radiologischen Verfahren wird diskutiert. Basierend auf der Einteilung der seronegativen Spondylarthropathien (SpA) sowie der rheumatoiden Arthritis (RA), erfolgte eine systematische Literaturrecherche. Die Ergebnisse dieser Recherche und die eigenen Erfahrungen mit einem grossen rheumatologischen Krankengut werden analysiert. Die Praevalenz der RA (1-2%) und der Gruppe der SpA (1,9%) ist vergleichbar, wobei die Aetiologie letztlich bei keiner der genannten Erkrankungen bekannt ist. Die bildmorphologische Kriterien koennen sich ueberlappen. Die MRT wird zunehmend bei Frueherkennung und Verlaufsbeurteilung der immunmodulatorischen Therapien (TNF-{alpha}-Antagonisten) eingesetzt. Ein Oedem im Knochen, das nur mit der MRT nachweisbar ist, zeigt die Aktivitaet der Entzuendung

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

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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.

Advances in the diagnosis and management of neck pain.

Science.gov (United States)

Cohen, Steven P; Hooten, W Michael

2017-08-14

Neck pain imposes a considerable personal and socioeconomic burden-it is one of the top five chronic pain conditions in terms of prevalence and years lost to disability-yet it receives a fraction of the research funding given to low back pain. Although most acute episodes resolve spontaneously, more than a third of affected people still have low grade symptoms or recurrences more than one year later, with genetics and psychosocial factors being risk factors for persistence. Nearly half of people with chronic neck pain have mixed neuropathic-nociceptive symptoms or predominantly neuropathic symptoms. Few clinical trials are dedicated solely to neck pain. Muscle relaxants and non-steroidal anti-inflammatory drugs are effective for acute neck pain, and clinical practice is mostly guided by the results of studies performed for other chronic pain conditions. Among complementary and alternative treatments, the strongest evidence is for exercise, with weaker evidence supporting massage, acupuncture, yoga, and spinal manipulation in different contexts. For cervical radiculopathy and facet arthropathy, weak evidence supports epidural steroid injections and radiofrequency denervation, respectively. Surgery is more effective than conservative treatment in the short term but not in the long term for most of these patients, and clinical observation is a reasonable strategy before surgery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Lack of predictive power of trait fear and anxiety for conditioned pain modulation (CPM).

Science.gov (United States)

Horn-Hofmann, Claudia; Priebe, Janosch A; Schaller, Jörg; Görlitz, Rüdiger; Lautenbacher, Stefan

2016-12-01

In recent years the association of conditioned pain modulation (CPM) with trait fear and anxiety has become a hot topic in pain research due to the assumption that such variables may explain the low CPM efficiency in some individuals. However, empirical evidence concerning this association is still equivocal. Our study is the first to investigate the predictive power of fear and anxiety for CPM by using a well-established psycho-physiological measure of trait fear, i.e. startle potentiation, in addition to two self-report measures of pain-related trait anxiety. Forty healthy, pain-free participants (female: N = 20; age: M = 23.62 years) underwent two experimental blocks in counter-balanced order: (1) a startle paradigm with affective picture presentation and (2) a CPM procedure with hot water as conditioning stimulus (CS) and contact heat as test stimulus (TS). At the end of the experimental session, pain catastrophizing (PCS) and pain anxiety (PASS) were assessed. PCS score, PASS score and startle potentiation to threatening pictures were entered as predictors in a linear regression model with CPM magnitude as criterion. We were able to show an inhibitory CPM effect in our sample: pain ratings of the heat stimuli were significantly reduced during hot water immersion. However, CPM was neither predicted by self-report of pain-related anxiety nor by startle potentiation as psycho-physiological measure of trait fear. These results corroborate previous negative findings concerning the association between trait fear/anxiety and CPM efficiency and suggest that shifting the focus from trait to state measures might be promising.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

Science.gov (United States)

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

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N. A. Shostak

2014-07-01

Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

BACK PAIN ASSOCIATED WITH INTERVERTEBRAL DISK DEGENERATION: MORPHOLOGICAL, GENETIC AND CLINICO-INSTRUMENTAL ASPECTS

Directory of Open Access Journals (Sweden)

N. A. Shostak

2011-01-01

Full Text Available Degenerative spine disease is one of the causes of back pain. Clinical types of pain and severity of inflammatory changes in the vertebral bodies depend on the activity of pro-inflammatory cytokines. Rate of development and progression of degenerative changes in the spine structures is genetically determined. Therapy of pain syndrome associated with a degenerative disc disease may include use of methods to restore damaged intervertebral disc structures, and also use of different combinations of anti-inflammatory and analgesics therapy.

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

Science.gov (United States)

Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

2017-01-01

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

Responsiveness of five condition-specific and generic outcome assessment instruments for chronic pain

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Verra Martin L

2008-04-01

Full Text Available Abstract Background Changes of health and quality-of-life in chronic conditions are mostly small and require specific and sensitive instruments. The aim of this study was to determine and compare responsiveness, i.e. the sensitivity to change of five outcome instruments for effect measurement in chronic pain. Methods In a prospective cohort study, 273 chronic pain patients were assessed on the Numeric Rating Scale (NRS for pain, the Short Form 36 (SF-36, the Multidimensional Pain Inventory (MPI, the Hospital Anxiety and Depression Scale (HADS, and the Coping Strategies Questionnaire (CSQ. Responsiveness was quantified by effect size (ES and standardized response mean (SRM before and after a four week in-patient interdisciplinary pain program and compared by the modified Jacknife test. Results The MPI measured pain more responsively than the SF-36 (ES: 0.85 vs 0.72, p = 0.053; SRM: 0.72 vs 0.60, p = 0.027 and the pain NRS (ES: 0.85 vs 0.62, p Conclusion The MPI was most responsive in all comparable domains followed by the SF-36. The pain-specific MPI and the generic SF-36 can be recommended for comprehensive and specific bio-psycho-social effect measurement of health and quality-of-life in chronic pain.

Vitamin D in Pain Management.

Science.gov (United States)

Helde-Frankling, Maria; Björkhem-Bergman, Linda

2017-10-18

Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like other hormones, vitamin D plays a role in a wide range of processes in the body. Here we review the possible role of vitamin D in nociceptive and inflammatory pain. In observational studies, low vitamin D levels have been associated with increased pain and higher opioid doses. Recent interventional studies have shown promising effects of vitamin D supplementation on cancer pain and muscular pain-but only in patients with insufficient levels of vitamin D when starting intervention. Possible mechanisms for vitamin D in pain management are the anti-inflammatory effects mediated by reduced cytokine and prostaglandin release and effects on T-cell responses. The recent finding of vitamin D-mediated inhibition of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible mechanistic explanation. Having reviewed current literature, we suggest that patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels 50 nmol/L probably have little benefit from supplementation. Our conclusion is that vitamin D may constitute a safe, simple and potentially beneficial way to reduce pain among patients with vitamin D deficiency, but that more randomized and placebo-controlled studies are needed before any firm conclusions can be drawn.

The interfaces between vitamin D, sleep and pain.

Science.gov (United States)

de Oliveira, Daniela Leite; Hirotsu, Camila; Tufik, Sergio; Andersen, Monica Levy

2017-07-01

The role of vitamin D in osteomineral metabolism is well known. Several studies have suggested its action on different biological mechanisms, such as nociceptive sensitivity and sleep-wake cycle modulation. Sleep is an important biological process regulated by different regions of the central nervous system, mainly the hypothalamus, in combination with several neurotransmitters. Pain, which can be classified as nociceptive, neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in the prevention and treatment of chronic pain conditions. © 2017 Society for Endocrinology.

Leaves extract of Murraya Koenigii linn for anti--inflammatory and analgesic activity in animal models

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Shailly Gupta

2010-01-01

Full Text Available This work has been done for the investigation of the anti-inflammatory and analgesic activity of methanol extract of dried leaves of Murraya koenigii Linn by oral administration at dose of 100, 200 and 400 mg/kg body weight, to healthy animals. Extract was studied for its anti-inflammatory activity by using carrageenan-induced hind paw edema in albino rats and the mean increase in paw volume and % inhibition in paw volume were measured plethysmometrically at different time intervals after carrageenan (1% w/v injection. Extract was also evaluated for analgesic activity using Eddy′s hot plate method and formalin induced paw licking method in albino rats. The methanol extract showed significant (P < 0.001 reduction in the carrageenan-induced paw edema and analgesic activity evidenced by increase in the reaction time by eddy′s hot plate method and percentage increase in pain in formalin test. The methanol extract showed anti-inflammatory and analgesic effect in dose dependent manner when compared with the control and standard drug, diclofenac sodium (10mg/kg, p.o. These inhibitions were statistically significant (P < 0.05. Thus our investigation suggests a potential benefit of Murraya koenigii in treating conditions associated with inflammatory pain.

Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

DEFF Research Database (Denmark)

Vægter, Henrik Bjarke; Handberg, Gitte; Graven-Nielsen, Thomas

2014-01-01

Pain inhibitory mechanisms are often assessed by paradigms of exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesised that the spatial and temporal manifestations of EIH and CPM were comparable. Eighty healthy subjects (40 females), between 18......-65 years participated in this randomized repeated-measures crossover trial with data collection on two different days. CPM was assessed by two different cold pressor tests (hand,foot). EIH was assessed through two intensities of aerobic bicycling exercises and two intensities of isometric muscle...... tests and after all of the exercise conditions, except low intensity bicycling. EIH after bicycling was increased in women compared to men. CPM and the EIH response after isometric exercises were comparable in men and women and not affected by age. The EIH response was larger in the exercising body part...

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

Science.gov (United States)

Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

2009-03-17

The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory

Systemic inflammatory mediators in post-traumatic Complex Regional Pain Syndrome (CRPS I - longitudinal investigations and differences to control groups

Directory of Open Access Journals (Sweden)

Schinkel Ch

2009-03-01

Full Text Available Abstract Objectives The Complex Regional Pain Syndrome I (CRPS I is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. Methods To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP, White Blood Cell Count (WBC, Interleukins 4, 6, 8, 10, 11, 12 (p70, Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-α and its soluble Receptors I/II, soluble Selectins (E, L, P, Substance-P (SP, and Calcitonin Gene-Related Peptide (CGRP at different time points in venous blood from patients with acute (AC and chronic (CC CRPS I, patients with forearm fractures (FR, with neuralgia (NE, and from healthy volunteers (C. Results No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007, FR/C (CGRP p = 0.048 and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049. High interindividual variations were observed. No intra-or interindividual correlation of parameters with clinical course (e.g. chronification or outcome was detectable. Conclusion Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this

Anti-inflammatory, anti-nociceptive and antipyretic potential of ...

African Journals Online (AJOL)

Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity.

The rat intervertebral disk degeneration pain model: relationships between biological and structural alterations and pain.

Science.gov (United States)

Kim, Jae-Sung; Kroin, Jeffrey S; Li, Xin; An, Howard S; Buvanendran, Asokumar; Yan, Dongyao; Tuman, Kenneth J; van Wijnen, Andre J; Chen, Di; Im, Hee-Jeong

2011-01-01

Degeneration of the interverterbral disk is as a cause of low-back pain is increasing. To gain insight into relationships between biological processes, structural alterations and behavioral pain, we created an animal model in rats. Disk degeneration was induced by removal of the nucleus pulposus (NP) from the lumbar disks (L4/L5 and L5/L6) of Sprague Dawley rats using a 0.5-mm-diameter microsurgical drill. The degree of primary hyperalgesia was assessed by using an algometer to measure pain upon external pressure on injured lumbar disks. Biochemical and histological assessments and radiographs of injured disks were used for evaluation. We investigated therapeutic modulation of chronic pain by administering pharmaceutical drugs in this animal model. After removal of the NP, pressure hyperalgesia developed over the lower back. Nine weeks after surgery we observed damaged or degenerated disks with proteoglycan loss and narrowing of disk height. These biological and structural changes in disks were closely related to the sustained pain hyperalgesia. A high dose of morphine (6.7 mg/kg) resulted in effective pain relief. However, high doses of pregabalin (20 mg/kg), a drug that has been used for treatment of chronic neuropathic pain, as well as the anti-inflammatory drugs celecoxib (50 mg/kg; a selective inhibitor of cyclooxygenase 2 (COX-2)) and ketorolac (20 mg/kg; an inhibitor of COX-1 and COX-2), did not have significant antihyperalgesic effects in our disk injury animal model. Although similarities in gene expression profiles suggest potential overlap in chronic pain pathways linked to disk injury or neuropathy, drug-testing results suggest that pain pathways linked to these two chronic pain conditions are mechanistically distinct. Our findings provide a foundation for future research on new therapeutic interventions that can lead to improvements in the treatment of patients with back pain due to disk degeneration.

Percutaneous renal sympathetic nerve ablation for loin pain haematuria syndrome.

Science.gov (United States)

Gambaro, Giovanni; Fulignati, Pierluigi; Spinelli, Alessio; Rovella, Valentina; Di Daniele, Nicola

2013-09-01

Loin pain haematuria syndrome (LPHS) is a severe renal pain condition of uncertain origin and often resistant to treatment. Nephrectomy and renal autotrasplantation have occasionally been performed in very severe cases. Its pathogenesis is controversial. A 40-year-old hypertensive lady was diagnosed with LPHS after repeated diagnostic imaging procedures had ruled out any renal, abdominal or spinal conditions to justify pain. Notwithstanding treatment with three drugs, she had frequent hypertensive crises during which the loin pain was dramatically exacerbated. Vascular causes of the pain and hypertension were investigated and excluded. Her renal function was normal. The patient was referred to a multidisciplinary pain clinic, but had no significant improvement in her pain symptoms despite the use of non-steroidal anti-inflammatory drugs, adjuvant antidepressants and opioid-like agents. The pain and the discomfort were so severe that her quality of life was very poor, and her social and professional activities were compromised. Nephrectomy and renal autotransplantation have occasionally been performed in these cases. Since visceral pain signals flow through afferent sympathetic fibres, we felt that percutaneous catheter-based radiofrequency ablation of the renal sympathetic nerve fibres (recently introduced for the treatment of drug-resistant hypertension) could be valuable for pain relief. We treated the patient with radiofrequency ablation (Medtronic Symplicity Catheter) applied only to the right renal artery. After a 6-month follow-up, the patient is pain free and normotensive with all drugs withdrawn. She has experienced no hypertensive crises in the meantime. This observation suggests that percutaneous sympathetic denervation could prove to be an effective mini-invasive strategy for the treatment of chronic renal pain, and LPHS in particular.

An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis

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Jason Hix

2017-12-01

Full Text Available Osteoarthritis (OA is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs were experienced by seven subjects (63.6%. There was one serious AE (diverticulitis unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement. There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

An Autologous Anti-Inflammatory Protein Solution Yielded a Favorable Safety Profile and Significant Pain Relief in an Open-Label Pilot Study of Patients with Osteoarthritis

Science.gov (United States)

Hix, Jason; Klaassen, Mark; Foreman, Ryan; Cullen, Edith; Toler, Krista; King, William; Woodell-May, Jennifer

2017-01-01

Abstract Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient's own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged “likely” to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores. PMID:29279807

An analysis of the various chronic pain conditions captured in a systematic review of active self-care complementary and integrative medicine therapies for the management of chronic pain symptoms.

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Lee, Courtney; Crawford, Cindy; Teo, Lynn; Spevak, Christopher

2014-04-01

Chronic pain management typically consists of prescription medications or provider-based, behavioral, or interventional procedures that are often ineffective, may be costly, and can be associated with undesirable side effects. Because chronic pain affects the whole person (body, mind, and spirit), patient-centered complementary and integrative medicine (CIM) therapies that acknowledge the patients' roles in their own healing processes have the potential to provide more efficient and comprehensive chronic pain management. Active self-care CIM therapies (ACT-CIM) allow for a more diverse, patient-centered treatment of complex symptoms, promote self-management, and are relatively safe and cost-effective. To date, there are no systematic reviews examining the full range of ACT-CIM used for chronic pain symptom management. A systematic review was conducted, using Samueli Institute's rapid evidence assessment of the literature (REAL©) methodology, to rigorously assess both the quality of the research on ACT-CIM modalities and the evidence for their efficacy and effectiveness in treating chronic pain symptoms. A working group of subject matter experts was also convened to evaluate the overall literature pool and develop recommendations for the use and implementation of these modalities. Following key database searches, 146 randomized controlled trials, covering 33 different pain conditions, were included in the review. This article categorized studies by pain condition, describing the diagnostic criteria used and modalities that seem most effective for each condition. Complexities associated with investigating chronic pain populations are also discussed. The entire scope of the review, categorized by modality rather than pain condition, is detailed throughout the current Pain Medicine supplement. Wiley Periodicals, Inc.

Cannabis and joints: scientific evidence for the alleviation of osteoarthritis pain by cannabinoids.

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O'Brien, Melissa; McDougall, Jason J

2018-04-07

Cannabis has been used for millennia to treat a multitude of medical conditions including chronic pain. Osteoarthritis (OA) pain is one of the most common types of pain and patients often turn to medical cannabis to manage their symptoms. While the majority of these reports are anecdotal, there is a growing body of scientific evidence which supports the analgesic potential of cannabinoids to treat OA pain. OA pain manifests as a combination of inflammatory, nociceptive, and neuropathic pain, each requiring modality-specific analgesics. The body's innate endocannabinoid system (ECS) has been shown to ameliorate all of these pain subtypes. This review summarizes the components of the ECS and details the latest research pertaining to plant-based and man-made cannabinoids for the treatment of OA pain. Recent pre-clinical evidence supporting a role for the ECS to control OA pain is described as well as current clinical evidence of the efficacy of cannabinoids for treating OA pain in mixed patient populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tapentadol extended-release for treatment of chronic pain: a review

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Vadivelu N

2011-08-01

Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

The Influence of Weather Conditions on Joint Pain in Older People with Osteoarthritis: Results from the European Project on OSteoArthritis.

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Timmermans, Erik J; Schaap, Laura A; Herbolsheimer, Florian; Dennison, Elaine M; Maggi, Stefania; Pedersen, Nancy L; Castell, Maria Victoria; Denkinger, Michael D; Edwards, Mark H; Limongi, Federica; Sánchez-Martínez, Mercedes; Siviero, Paola; Queipo, Rocio; Peter, Richard; van der Pas, Suzan; Deeg, Dorly J H

2015-10-01

This study examined whether daily weather conditions, 3-day average weather conditions, and changes in weather conditions influence joint pain in older people with osteoarthritis (OA) in 6 European countries. Data from the population-based European Project on OSteoArthritis were used. The American College of Rheumatology classification criteria were used to diagnose OA in older people (65-85 yrs). After the baseline interview, at 6 months, and after the 12-18 months followup interview, joint pain was assessed using 2-week pain calendars. Daily values for temperature, precipitation, atmospheric pressure, relative humidity, and wind speed were obtained from local weather stations. Multilevel regression modelling was used to examine the pain-weather associations, adjusted for several confounders. The study included 810 participants with OA in the knee, hand, and/or hip. After adjustment, there were significant associations of joint pain with daily average humidity (B = 0.004, p weather conditions. Changes in weather variables between 2 consecutive days were not significantly associated with reported joint pain. The associations between pain and daily average weather conditions suggest that a causal relationship exist between joint pain and weather variables, but the associations between day-to-day weather changes and pain do not confirm causation. Knowledge about the relationship between joint pain in OA and weather may help individuals with OA, physicians, and therapists to better understand and manage fluctuations in pain.

Survey of Thai Physicians Regarding Recognition and Management of Inflammatory Back Pain and Spondyloarthritis.

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Tangrungruengkit, Mintra; Srinonprasert, Varalak; Chiowchanwisawakit, Praveena

2016-01-01

To assess recognition and management of inflammatory back pain (IBP) and spondyloarthritis (SpA) among non-rheumatologists (NRs) and rheumatologists in Thailand. A cross-sectional survey was conducted among physicians in Thailand A questionnaire designed to evaluate knowledge regarding IBP and SpA was sent to 1,336 NRs. A different questionnaire regarding SpA management in practice was sent to 112 rheumatologists. Of 1,448 questionnaires distributed, 367 (25.3%) questionnaires were returned (NRs: 321 [24.0%] and included rheumatologists, 46 [41.1%]). Among NRs, 26.6%, 20.9%, and 9.4% recognized all features of IBP according to Calin, Assessment of SpondyloArthritis International Society, and Berlin criteria, respectively. In the presence of typical features of ankylosing spondylitis, 57.8% of NRs made the correct diagnosis. Regarding related clinical skills and involvement, 43.8%, 53.6%, and 37.3% of NRs lacked confidence in distinguishing IBP from mechanical back pain, performing musculoskeletal examination, and interpretation of plain radiography, respectively. Expensive biologic agents (31.2%) and advanced disease stage at diagnosis (27.1%) were the main problems reported by rheumatologists. Problems in diagnosis and management of SpA patients among NRs in Thailand included lack of knowledge and lack of associated clinical skills. Issues reported by rheumatologists centered on case management limitations. In order to improve overall quality of care for SpA patients, focused strategies should be implemented for both NRs and rheumatologists that consider the needs of patients, clinicians, and policy makers.

Postpartum Inflammatory Sacroiliitis-A Case Report

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Seniz Akcay Yalbuzdag

2013-08-01

Full Text Available During the pregnancy several changes occur in sacroiliac joint and pelvis which may predispose for sacroiliac joint strain and septic sacroiliitis. We describe a case of acute inflammatory sacroiliitis in a patient with HLA B27 positivity during postpartum period, and diagnosed psoriatic arthritis during the follow up period. We aimed to emphasize that inflammatory sacroiliitis should take place whithin differantial diagnose of postpartum low back pain.

Pain, functional status, social function and conditions of habitation in elderly unilaterally lower limb amputees

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Đurović Aleksandar

2007-01-01

Full Text Available Background/Aim. Few authors are involved in home rehabilitation of amputees or their reintegration into the community. It has been remarked that there is a discontinuity between the phases of the amputee rehabilitation in Serbia. The aim of the study was to establish pain characteristics and functional status of amputees two months after the amputation and to determine their social function and the conditions of their habitation. Methods. This prospective observation study involved 38 elderly amputees with unilateral lower limb amputations. The patients were tested at the hospital on discharge and at their homes two months after the amputation. Pain intensity and functional status were measured by a visual analogue scale (VAS and by Functional Independence Measure (FIM. The patients’ social function was assessed using the Social Dysfunction Rating Scale (SDRS and conditions of their habitation by the self-created Scale of Conditions of Habitation (SCH. In statistic analysis we used the Student t test, χ2 test and Analysis of variance (ANOVA. Results. The majority of patients (63% underwent below knee amputation caused by diabetes (89%. A significant number of patients (84%, χ2 = 17.78; p < 0.01 was not visited by a physiotherapist nor an occupational therapist during two months at home. In this period, the majority of the amputees (68% had phantom pain or residual limb pain (21%. Two months after amputation the pain intensity was significantly lower (VAS = 4.07±2.19; 2.34±1.41; p < 0.001, and the functional status significantly better than on discharge (FIM = 75.13±16.52; 87.87±16.48; p < 0.001. The amputees had the average level of social dysfunction (SDRS = 62.00±11.68 and conditions of habitation (SCH = 7.81±1.97. Conclusion. A total 38 elderly amputees with unilateral lower limb amputations achieved significant functional improvement and reduction of pain, in spite of their social dysfunction, the absence of socio-medical support

Waning of "conditioned pain modulation": a novel expression of subtle pronociception in migraine.

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Nahman-Averbuch, Hadas; Granovsky, Yelena; Coghill, Robert C; Yarnitsky, David; Sprecher, Elliot; Weissman-Fogel, Irit

2013-01-01

To assess the decay of the conditioned pain modulation (CPM) response along repeated applications as a possible expression of subtle pronociception in migraine. One of the most explored mechanisms underlying the pain modulation system is "diffuse noxious inhibitory controls," which is measured psychophysically in the lab by the CPM paradigm. There are contradicting reports on CPM response in migraine, questioning whether migraineurs express pronociceptive pain modulation. Migraineurs (n = 26) and healthy controls (n = 35), all females, underwent 3 stimulation series, consisting of repeated (1) "test-stimulus" (Ts) alone that was given first followed by (2) parallel CPM application (CPM-parallel), and (3) sequential CPM application (CPM-sequential), in which the Ts is delivered during or following the conditioning-stimulus, respectively. In all series, the Ts repeated 4 times (0-3). In the CPM series, repetition "0" consisted of the Ts-alone that was followed by 3 repetitions of the Ts with a conditioning-stimulus application. Although there was no difference between migraineurs and controls for the first CPM response in each series, we found waning of CPM-parallel efficiency along the series for migraineurs (P = .005 for third vs first CPM), but not for controls. Further, greater CPM waning in the CPM-sequential series was correlated with less reported extent of pain reduction by episodic medication (r = 0.493, P = .028). Migraineurs have subtle deficits in endogenous pain modulation which requires a more challenging test protocol than the commonly used single CPM. Waning of CPM response seems to reveal this pronociceptive state. The clinical relevance of the CPM waning effect is highlighted by its association with clinical parameters of migraine. © 2013 American Headache Society.

Anti-inflammatory drugs in the 21st century.

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Rainsford, K D

2007-01-01

physiological processes whose inhibition was considered a major factor in development of adverse reactions, including those in the GI tract. At the turn of this century, there was enormous commercial development following the introduction of two new highly selective COX-2 inhibitors, known as coxibs (celecoxib and rofecoxib) which were claimed to have low GI side effects. While found to have fulfilled these aims in part, an alarming turn of events took place in the late 2004 period when rofecoxib was withdrawn worldwide because of serious cardiovascular events and other coxibs were subsequently suspected to have this adverse reaction, although to a varying degree. Major efforts are currently underway to discover why cardiovascular reactions took place with coxibs, identify safer coxibs, as well as elucidate the roles of COX-2 and COX-1 in cardiovascular diseases and stroke in the hope that there may be some basis for developing newer agents (e.g. nitric oxide-donating NSAIDs) to control these conditions. The discovery of the COX isoforms led to establishing their importance in many non-arthritic or non-pain states where there is an inflammatory component to pathogenesis, including cancer, Alzheimer's and other neurodegenerative diseases. The applications of NSAIDs and the coxibs in the prevention and treatment of these conditions as well as aspirin and other analogues in the prevention of thrombo-embolic diseases now constitute one of the major therapeutic developments of the this century. Moreover, new anti-inflammatory drugs are being discovered and developed based on their effects on signal transduction and as anti-cytokine agents and these drugs are now being heralded as the new therapies to control those diseases where cytokines and other nonprostaglandin components of chronic inflammatory and neurodegenerative diseases are manifest. To a lesser extent safer application of corticosteroids and the applications of novel drug delivery systems for use with these drugs as well

Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: Results of a randomized controlled pilot study

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Goodin, Burel R.; Quinn, Noel B.; Kronfli, Tarek; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

2011-01-01

Objective Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms. Design Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble receptor of tumor necrosis factor-α (sTNFαRII). Results Compared to the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized. Conclusions Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines. PMID:22233394

Non-Steroidal Anti Inflammatory Drugs Usage In Orthopaedics And ...

African Journals Online (AJOL)

Background: Non steroidal anti-inflammatory drugs NSAIDs) are a group of heterogeneous compounds with nti inflammatory, analgesic and often times anti pyretic roperties. They are weak organic acids and are the most commonly used drugs in Orthopaedic/Trauma practice. hey provide mild to moderate pain relief.

Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

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Inayama Yoshiaki

2010-02-01

Full Text Available Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.

Contingency Awareness Shapes Acquisition and Extinction of Emotional Responses in a Conditioning Model of Pain-Related Fear.

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Labrenz, Franziska; Icenhour, Adriane; Benson, Sven; Elsenbruch, Sigrid

2015-01-01

As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies. In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US) were repeatedly paired with a predictive visual cue (conditioned stimulus; CS(+)) while another cue (CS(-)) was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analog scales (VAS). Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low vs. high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS(+) and increased positive responses to CS(-) when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS(+) and CS

Contingency awareness shapes acquisition and extinction of emotional responses in a conditioning model of pain-related fear

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Franziska eLabrenz

2015-11-01

Full Text Available As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically-significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies.In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US were repeatedly paired with a predictive visual cue (conditioned stimulus; CS+ while another cue (CS- was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analogue scales. Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low versus high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS+ and increased positive responses to CS- when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS+ and

The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat

DEFF Research Database (Denmark)

Munro, G; Hansen, Rikke Rie; Erichsen, Hk

2012-01-01

BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators. Increasin......BACKGROUND AND PURPOSE: Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti-hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro-inflammatory mediators...

Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling

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Sidra Khalid

2018-03-01

Full Text Available The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p. honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p. with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, and vascular endothelial growth factor (VEGF. Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2, superoxide dismutase 2 (SOD2, and heme oxygenase-1 (HO-1 levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA induced group. X-ray analysis and hematoxylin and eosin (H&E staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg, tramadol (50 mg/kg, and gabapentin (5 mg/kg i.p.] as well as antagonists [naloxone (4 mg/kg, olanzapine (10 mg/kg, and flumazenil (0.2 mg/kg i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by

Groin pain and iliopsoas bursitis: always a cause-effect relationship?

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Di Sante, Luca; Paoloni, Marco; De Benedittis, Stefano; Tognolo, Lucrezia; Santilli, Valter

2014-01-01

Iliopsoas bursitis (IB) is characterized by inflammation and enlargement of the iliopsoas bursa. Although this condition is often associated with degenerative or inflammatory arthritis, infections, trauma, overuse and impingement syndromes, osteonecrosis and hip replacement, the pathogenesis of IB remains uncertain. We present a case report of IB associated with moderate hip osteoarthritis (HOA). We present a case report of a 73-year-old man with chronic left hip pain that did not respond to conservative treatments. An ultrasonography examination of the left hip revealed fluid-induced distension of the iliopsoas bursa, which was treated with aspiration followed by a corticosteroid-anesthetic injection. At the 30-day follow-up, despite an initial improvement in the patient's symptoms, both the pain and functional limitation returned, though not in association with bursa distension. The patient therefore underwent a total hip arthroplasty, which fully relieved the symptoms. We hypothesize that iliopsoas bursitis may, when associated with other pathological conditions, not be the only source of pain. It should, nevertheless, be considered for differential diagnosis purposes.

Neuropathic pain, depressive symptoms, and C-reactive protein in sciatica patients.

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Uher, Tomas; Bob, Petr

2013-03-01

There is evidence that neuropathic pain component in low back pain (LBP) patients is associated with higher ratings of comorbidities such as depression and anxiety disorders. In line with current findings, the purpose of this clinical study is to examine a hypothesis regarding a relationship of neuropathic pain component, depression, and other psychopathological symptoms in a specific group of LBP patients with sciatica pain. With respect to findings that depression is related to inflammatory changes, and inflammatory mediators may play a role in neuropathic pain generation, we have assessed also serum C-reactive protein (CRP). Results of the present study show that increased neuropathic pain component in sciatica patients is associated with elevated levels of depression, anxiety, alexithymia, and serum CRP levels. In conclusion, results of this study indicate that CRP levels in sciatica patients are closely associated with neuropathic pain.

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.

Pain management in lung cancer.

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Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

2016-01-01

Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

Control of pain with topical plant medicines

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James David Adams Jr.

2015-04-01

Full Text Available Pain is normally treated with oral nonsteroidal anti-inflammatory agents and opioids. These drugs are dangerous and are responsible for many hospitalizations and deaths. It is much safer to use topical preparations made from plants to treat pain, even severe pain. Topical preparations must contain compounds that penetrate the skin, inhibit pain receptors such as transient receptor potential cation channels and cyclooxygenase-2, to relieve pain. Inhibition of pain in the skin disrupts the pain cycle and avoids exposure of internal organs to large amounts of toxic compounds. Use of topical pain relievers has the potential to save many lives, decrease medical costs and improve therapy.

Out-of-Pocket Expenditures on Complementary Health Approaches Associated with Painful Health Conditions in a Nationally Representative Adult Sample

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Nahin, Richard L.; Stussman, Barbara J.; Herman, Patricia M.

2015-01-01

National surveys suggest that millions of adults in the United States use complementary health approaches such as acupuncture, chiropractic manipulation, and herbal medicines to manage painful conditions such as arthritis, back pain and fibromyalgia. Yet, national and per person out-of-pocket (OOP) costs attributable to this condition-specific use are unknown. In the 2007 National Health Interview Survey, use of complementary health approaches, reasons for this use, and associated OOP costs were captured in a nationally representative sample of 5,467 adults. Ordinary least square regression models that controlled for co-morbid conditions were used to estimate aggregate and per person OOP costs associated with 14 painful health conditions. Individuals using complementary approaches spent a total of $14.9 billion (S.E. $0.9 billion) OOP on these approaches to manage these painful conditions. Total OOP expenditures seen in those using complementary approaches for their back pain ($8.7 billion, S.E. $0.8 billion) far outstripped that of any other condition, with the majority of these costs ($4.7 billion, S.E. $0.4 billion) resulting from visits to complementary providers. Annual condition-specific per-person OOP costs varied from a low of $568 (SE $144) for regular headaches, to a high of $895 (SE $163) for fibromyalgia. PMID:26320946

[Correlation analysis of bone marrow edema degree and serum inflammatory factors change with knee joint pain symptoms in patients with bone contusion around the knee joint].

Science.gov (United States)

Li, Songiun; An, Rongze; Wang, Zhaojie; Kuang, Lipeng; Tan, Weiyuan; Fang, Cunxun

2014-05-01

To explore the correlation between the degree of bone marrow edema (BME) and the content change of tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP-3) and the knee pain symptoms in patients with bone contusion around the knee joint. Thirty patients (30 knees) of bone contusion around the knee joint were chosen as the trial group between October 2009 and April 2012. According to visual analogue scale (VAS), 30 patients were divided into mild group (10 cases), moderate group (10 cases), and severe group (10 cases); according to MRI morphological changes, the patients were divided into type I group (12 cases), type II group (11 cases), and type III group (7 cases). Ten patients (10 knees) with soft tissue injury of the knee were chosen as control group. No significant difference was found (P > 0.05) in gender, age, causes, side, and admission time after injury between 2 groups. The serum contents of MMP-3 and TNF-alpha were detected and statistically analysed between different degrees of pain groups and between different degrees of BME groups. Correlation was analysed between BME and inflammatory factor changes and VAS score. The MMP-3 and TNF-alpha contents in trial group [(29.580 +/- 6.870) (microg/L and (23.750 +/- 7.096) ng/L] were significantly higher than those in control group [(8.219 +/- 1.355) microg/L and (6.485 +/- 1.168) ng/L] (t = 9.686, P = 0.000; t = 7.596, P =0.000). The MMP-3 and TNF-alpha contents in patients with different degrees of pain and BME were significantly higher than those in patients of control group (P pain (P 0.05). Multiple linear regression analysis showed that TNF-alpha content was significantly correlated with VAS score (P = 0.000). Knee pain symptoms are not related to the degree of BME in patients with bone contusion around the knee joint. Inflammatory factor TNF-alpha content is the main influence factor of knee joint pain symptoms.

Radiologic imaging of degenerative and inflammatory joint disorders in women

International Nuclear Information System (INIS)

Krestan, C.R.; Grampp, S.; Kainberger . christian.krestan@univie.ac.at

2001-01-01

Pain in joints and other structures of the musculoskeletal system is a common complaint in women. It may occur as functional pain, in many cases as inflammatory episode of arthrosis or of metabolic joint disease, sometimes as early manifestation of rheumatoid disease. With conventional radiography, high resolution sonography, and MR imaging it is possible to classify many of these clinical syndromes. A semiquantitative assessment of inflammatory activity can be made by analysing the degree of joint effusion, the thickness of the synovium and the extent of hypervascularization. (author)

[Cholinergic anti-inflammatory pathway of some non-pharmacological therapies of complementary medicine: possible implications for treatment of rheumatic and autoimmune diseases].

Science.gov (United States)

Gamus, Dorit

2011-08-01

Rheumatologic and autoimmune diseases are among foremost diseases for which patients seek complementary and integrative medicine options. Therefore, physicians should be informed on the advances in research of these therapies, in order to be able to discuss possible indications and contraindications for these treatment modalities with their patients. This review summarizes several therapeutic modalities of complementary medicine that may be involved in the cholinergic anti-inflammatory pathway. The analysis of systematic reviews of acupuncture for rheumatic conditions has concluded that the evidence is sufficiently sound to warrant positive recommendations of this therapy for osteoarthritis, low back pain and lateral elbow pain. There is relatively strong evidence to support the use of hypnosis in pain treatment, such as in cases of fibromyalgia. A recent controlled study that evaLuated tai-chi in fibromyalgia has reported reductions in pain, improvements in mood, quality of Life, self efficacy and exercise capacity. There is also cumulative evidence that acupuncture, hypnosis and tai-chi may decrease the high frequency of heart rate variability, suggesting enhancement of vagus nerve activity. Hence, it has been hypothesized that these modalities might impact the cholinergic anti-inflammatory pathway to modulate inflammation. Further clinical and basic research to confirm this hypothesis should be performed in order to validate integration of these therapies in comprehensive treatment for some inflammatory and autoimmune diseases.

Complex Regional Pain Syndrome: An inflammatory disease

NARCIS (Netherlands)

M. Dirckx (Maaike)

2015-01-01

markdownabstractThe pathophysiology of Complex Regional Pain Syndrome (CRPS) is complex and still not completely understood. In addition to a convincing role of inflammation, there are a number of arguments why an involvement of the immune system has been suggested in the pathophysiology of CRPS.

The Effect of Gabapentin and Tramadol in Cancer Pain Induced by Glioma Cell in Rat Femur.

Science.gov (United States)

Corona-Ramos, Janette Nallely; Déciga-Campos, Myrna; Romero-Piña, Mario; Medina, Luis A; Martínez-Racine, Issac; Jaramillo-Morales, Osmar A; García-López, Patricia; López-Muñoz, Francisco Javier

2017-08-01

Preclinical Research The presence of pain as part of the cancer process is variable. Glioblastoma multiform (GBM) can produce bone metastasis, a condition that involves other pathological phenotypes including neuropathic and inflammatory pain. Tramadol and gabapentin are drugs used in the treatment of neuropathic pain. However, there are no studies evaluating their analgesic effects in bone metastasis. We produced a pain model induced by the inoculation of glioma cells (10 5 ) into the rat femur, by perforating the intercodiloid fossa. Painful behavior was evaluated by measuring mechanical allodynia using the Von Frey test while thermal hyperalgesia was assessed in the plantar test. Histopathological features were evaluated and antinociceptive responses were compared using tramadol and gabapentin. The inoculation of cells inside the right femur produced nociceptive behaviors. Tramadol and gabapentin produced an anti-allodynic effect in this condition, but tramadol did not produce an anti-hyperalgesic response. The development of this model will allow us to perform tests to elucidate the pathology of bone metastasis, cancer pain, and in particular the pain produced by glioma. Drug Dev Res 78 : 173-183, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel.

Science.gov (United States)

Santos Garcia, Joäo Batista; Lech, Osvandré; Campos Kraychete, Durval; Rico, María Antonieta; Hernández-Castro, John Jairo; Colimon, Frantz; Guerrero, Carlos; Sempértegui Gallegos, Manuel; Lara-Solares, Argelia; Flores Cantisani, José Alberto; Amescua-Garcia, César; Guillén Núñez, María Del Rocío; Berenguel Cook, María Del Rosario; Jreige Iskandar, Aziza; Bonilla Sierra, Patricia

2017-09-01

Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol's role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol's high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics - mainly controlled drugs (classical opioids) - is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients.

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions

DEFF Research Database (Denmark)

Kent, Michael L; Tighe, Patrick J; Belfer, Inna

2017-01-01

the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership...... with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain...... Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria...

Inhibitory effects of aspirin-triggered resolvin D1 on spinal nociceptive processing in rat pain models.

Science.gov (United States)

Meesawatsom, Pongsatorn; Burston, James; Hathway, Gareth; Bennett, Andrew; Chapman, Victoria

2016-09-02

Harnessing the actions of the resolvin pathways has the potential for the treatment of a wide range of conditions associated with overt inflammatory signalling. Aspirin-triggered resolvin D1 (AT-RvD1) has robust analgesic effects in behavioural models of pain; however, the potential underlying spinal neurophysiological mechanisms contributing to these inhibitory effects in vivo are yet to be determined. This study investigated the acute effects of spinal AT-RvD1 on evoked responses of spinal neurones in vivo in a model of acute inflammatory pain and chronic osteoarthritic (OA) pain and the relevance of alterations in spinal gene expression to these neurophysiological effects. Pain behaviour was assessed in rats with established carrageenan-induced inflammatory or monosodium iodoacetate (MIA)-induced OA pain, and changes in spinal gene expression of resolvin receptors and relevant enzymatic pathways were examined. At timepoints of established pain behaviour, responses of deep dorsal horn wide dynamic range (WDR) neurones to transcutaneous electrical stimulation of the hind paw were recorded pre- and post direct spinal administration of AT-RvD1 (15 and 150 ng/50 μl). AT-RvD1 (15 ng/50 μl) significantly inhibited WDR neurone responses to electrical stimuli at C- (29 % inhibition) and Aδ-fibre (27 % inhibition) intensities. Both wind-up (53 %) and post-discharge (46 %) responses of WDR neurones in carrageenan-treated animals were significantly inhibited by AT-RvD1, compared to pre-drug response (p < 0.05). These effects were abolished by spinal pre-administration of a formyl peptide receptor 2 (FPR2/ALX) antagonist, butoxy carbonyl-Phe-Leu-Phe-Leu-Phe (BOC-2) (50 μg/50 μl). AT-RvD1 did not alter evoked WDR neurone responses in non-inflamed or MIA-treated rats. Electrophysiological effects in carrageenan-inflamed rats were accompanied by a significant increase in messenger RNA (mRNA) for chemerin (ChemR23) receptor and 5-lipoxygenase

[Ultrasonography in acute pelvic pain].

Science.gov (United States)

Kupesić, Sanja; Aksamija, Alenka; Vucić, Niksa; Tripalo, Ana; Kurjak, Asim

2002-01-01

Acute pelvic pain may be the manifestation of various gynecologic and non-gynecologic disorders from less alarming rupture of the follicular cyst to life threatening conditions such as rupture of ectopic pregnancy or perforation of inflamed appendix. In order to construct an algorithm for differential diagnosis we divide acute pelvic pain into gynecologic and non-gynecologic etiology, which is than subdivided into gastrointestinal and urinary causes. Appendicitis is the most common surgical emergency and should always be considered in differential diagnosis if appendix has not been removed. Apart of clinical examination and laboratory tests, an ultrasound examination is sensitive up to 90% and specific up to 95% if graded compression technique is used. Still it is user-depended and requires considerable experience in order to perform it reliably. Meckel's diverticulitis, acute terminal ileitis, mesenteric lymphadenitis and functional bowel disease are conditions that should be differentiated from other causes of low abdominal pain by clinical presentation, laboratory and imaging tests. Dilatation of renal pelvis and ureter are typical signs of obstructive uropathy and may be efficiently detected by ultrasound. Additional thinning of renal parenchyma suggests long-term obstructive uropathy. Ruptured ectopic pregnancy, salpingitis and hemorrhagic ovarian cysts are three most commonly diagnosed gynecologic conditions presenting as an acute abdomen. Degenerating leiomyomas and adnexal torsion occur less frequently. For better systematization, gynecologic causes of acute pelvic pain could be divided into conditions with negative pregnancy test and conditions with positive pregnancy test. Pelvic inflammatory disease may be ultrasonically presented with numerous signs such as thickening of the tubal wall, incomplete septa within the dilated tube, demonstration of hyperechoic mural nodules, free fluid in the "cul-de-sac" etc. Color Doppler ultrasound contributes to more

Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis.

Science.gov (United States)

Bermudez, Maria A; Sendon-Lago, Juan; Seoane, Samuel; Eiro, Noemi; Gonzalez, Francisco; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

2016-08-01

The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'ìn vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro-inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM-hUCESCs to determine mediating proteins. Results showed that administration of CM-hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic pelvic pain

African Journals Online (AJOL)

misdiagnoses, inappropriate or inadequate treatment strategies, and poor patient compliance .... excitation tenderness implies an active pelvic inflammatory process. Pain localising to ... neoplastic process, particularly cervical cancer, must be excluded. .... The dosage should be started at 10 mg at night, and increased by 5 ...

Corrosion and mechanical performance of AZ91 exposed to simulated inflammatory conditions.

Science.gov (United States)

Brooks, Emily K; Der, Stephanie; Ehrensberger, Mark T

2016-03-01

Magnesium (Mg) and its alloys, including Mg-9%Al-1%Zn (AZ91), are biodegradable metals with potential use as temporary orthopedic implants. Invasive orthopedic procedures can provoke an inflammatory response that produces hydrogen peroxide (H2O2) and an acidic environment near the implant. This study assessed the influence of inflammation on both the corrosion and mechanical properties of AZ91. The AZ91 samples in the inflammatory protocol were immersed for three days in a complex biologically relevant electrolyte (AMEM culture media) that contained serum proteins (FBS), 150 mM of H2O2, and was titrated to a pH of 5. The control protocol immersed AZ91 samples in the same biologically relevant electrolyte (AMEM & FBS) but without H2O2 and the acid titration. After 3 days all samples were switched into fresh AMEM & FBS for an additional 3-day immersion. During the initial immersion, inflammatory protocol samples showed increased corrosion rate determined by mass loss testing, increased Mg and Al ion released to solution, and a completely corroded surface morphology as compared to the control protocol. Although corrosion in both protocols slowed once the test electrolyte solution was replaced at 3 days, the samples originally exposed to the simulated inflammatory conditions continued to display enhanced corrosion rates as compared to the control protocol. These lingering effects may indicate the initial inflammatory corrosion processes modified components of the surface oxide and corrosion film or initiated aggressive localized processes that subsequently left the interface more vulnerable to continued enhanced corrosion. The electrochemical properties of the interfaces were also evaluated by EIS, which found that the corrosion characteristics of the AZ91 samples were potentially influenced by the role of intermediate adsorption layer processes. The increased corrosion observed for the inflammatory protocol did not affect the flexural mechanical properties of the AZ91

AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions

OpenAIRE

Paice, Judith A.; Mulvey, Matt; Bennett, Michael; Dougherty, Patrick M.; Farrar, John T.; Mantyh, Patrick W.; Miaskowski, Christine; Schmidt, Brian; Smith, Thomas J.

2016-01-01

Chronic cancer pain is a serious complication of malignancy or its treatment. Currently, no comprehensive, universally accepted cancer pain classification system exists. Clarity in classification of common cancer pain syndromes would improve clinical assessment and management. Moreover, an evidence-based taxonomy would enhance cancer pain research efforts by providing consistent diagnostic criteria, ensuring comparability across clinical trials. As part of a collaborative effort between the A...

Antinociceptive and anti-exudative synergism between dexketoprofen and tramadol in a model of inflammatory pain in mice.

Science.gov (United States)

Miranda, Hugo F; Romero, Maria Asunción; Puig, Margarita M

2012-06-01

Preclinical studies have demonstrated antinociceptive synergism between dexketoprofen (DEX) and tramadol (TRM) in acute animal models of nociception. The aim of the present study was to investigate the type of interaction between DEX and TRM in a chronic musculoskeletal pain model in mice, which fairly replicates the characteristics of chronic osteoarticular pain in humans. Inflammation was induced by a subplantar injection of complete Freund's adjuvant (CFA) in male CF1 mice. Nociceptive thresholds were evaluated using the hot plate, the nocifensive spontaneous behavior and the acetone tests, while plasma extravasation (PE) was assessed with Evan's blue. We used the following experimental groups: control (no inflammation), acute (1 day after CFA injection), and chronic inflammation (7 days after CFA). Dose-response curves for DEX and TRM, individually and combined in a 1 : 1 proportion based on their potency were obtained, and the doses that produced a 50% inhibition calculated. The isobolographic analysis revealed that in all groups of study (no inflammation, acute, and chronic inflammation), the combination of DEX : TRM was synergistic, for both the inhibition of nociception and the PE. The results suggest that the DEX : TRM (1 : 1) combination could be useful in the management of acute and chronic inflammatory musculoskeletal pains in humans; in addition, the synergistic interaction between the drugs observed both during acute and chronic inflammation suggests that less doses would be required of each drug to obtain effective analgesia. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative

NARCIS (Netherlands)

Whittle, Samuel L.; Colebatch, Alexandra N.; Buchbinder, Rachelle; Edwards, Christopher J.; Adams, Karen; Englbrecht, Matthias; Hazlewood, Glen; Marks, Jonathan L.; Radner, Helga; Ramiro, Sofia; Richards, Bethan L.; Tarner, Ingo H.; Aletaha, Daniel; Bombardier, Claire; Landewé, Robert B.; Müller-Ladner, Ulf; Bijlsma, Johannes W. J.; Branco, Jaime C.; Bykerk, Vivian P.; da Rocha Castelar Pinheiro, Geraldo; Catrina, Anca I.; Hannonen, Pekka; Kiely, Patrick; Leeb, Burkhard; Lie, Elisabeth; Martinez-Osuna, Píndaro; Montecucco, Carlomaurizio; Ostergaard, Mikkel; Westhovens, Rene; Zochling, Jane; van der Heijde, Désirée

2012-01-01

To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists

Evaluation of a nanotechnology-based approach to induce gene-expression in human THP-1 macrophages under inflammatory conditions.

Science.gov (United States)

Bernal, Laura; Alvarado-Vázquez, Abigail; Ferreira, David Wilson; Paige, Candler A; Ulecia-Morón, Cristina; Hill, Bailey; Caesar, Marina; Romero-Sandoval, E Alfonso

2017-02-01

Macrophages orchestrate the initiation and resolution of inflammation by producing pro- and anti-inflammatory products. An imbalance in these mediators may originate from a deficient or excessive immune response. Therefore, macrophages are valid therapeutic targets to restore homeostasis under inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle effectively induces gene expression in human macrophages under inflammatory conditions without undesirable immunogenic responses. THP-1 macrophages were challenged with lipopolysaccharide (LPS, 5μg/mL). Polyethylenimine (PEI) nanoparticles grafted with a mannose receptor ligand (Man-PEI) were used as a gene delivery method. Nanoparticle toxicity, Man-PEI cellular uptake rate and gene induction efficiency (GFP, CD14 or CD68) were studied. Potential immunogenic responses were evaluated by measuring the production of tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-10. Man-PEI did not produce cytotoxicity, and it was effectively up-taken by THP-1 macrophages (69%). This approach produced a significant expression of GFP (mRNA and protein), CD14 and CD68 (mRNA), and transiently and mildly reduced IL-6 and IL-10 levels in LPS-challenged macrophages. Our results indicate that Man-PEI is suitable for inducing an efficient gene overexpression in human macrophages under inflammatory conditions with limited immunogenic responses. Our promising results set the foundation to test this technology to induce functional anti-inflammatory genes. Copyright © 2016 Elsevier GmbH. All rights reserved.