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Sample records for chronic neuropathic pain

  1. Neuropathic pain

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    Giuseppe Re

    2009-02-01

    Full Text Available Neuropathic pain is the expression of a dysfunction or primary lesion of a nerve in the peripheral or central nervous system, or both, rather than the biological signal transmitted by the nerve following peripheral nociceptor activation. It represents about 20% of all painful syndromes, with an estimated prevalence of 1.5%, however is actual incidence is hard to pinpoint due to the difficulties encountered in distinguishing it from chronic pain, of which it represents a significant percentage, on account of the not infrequent concurrence of conditions. It is crucial to recognise the variety of symptoms with which it can present: these can be negative and positive and, in turn, motor, sensitive and autonomic. In public health terms, it is important to emphasise that the diagnosis of neuropathic pain does not in most cases require sophisticated procedures and does not therefore weigh on health expenditure. In clinical practice, a validated scale (the LANSS is mentioned is useful for identifying patients presenting neuropathic pain symptoms. Therapy is based on three categories of medication: tricyclic antidepressants, anti-epileptics and opioids at high doses: neuropathic pain has a bad reputation for often resisting common therapeutic approaches and responding less well that nociceptor pain to monotherapy. Therapeutic strategies are all the more adequate the more they are based on symptoms and therefore on the pain generation mechanisms, although the recommendations are dictated more by expert opinions that double-blind randomised trials.

  2. Evidence-based pharmacological management of chronic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zarrin Ansari

    2013-06-01

    Full Text Available Neuropathic pain (NP is a chronic, debilitating symptomatology of lesions/injuries of the central and peripheral nervous system. As per pooled estimates, the prevalence is 7-8% in the general population; however, the prevalence varies with different neuropathic conditions. The aetiology can range from peripheral neuropathic conditions viz. peripheral diabetic neuropathic pain (PDNP, post-herpetic neuralgia (PHN, trigeminal neuralgia, HIV- associated polyneuropathy, cervical radiculopathy to central neuropathic conditions, viz. central post-stroke pain, spinal cord injury and the neuropathic pain associated with multiple sclerosis. Apart from the symptomatic perception of pain, neuropathic pain affects the cognitive and emotional aspects of the affected individual. The pain, being debilitating and resistant to over-the-counter analgesics, diminishes the quality of life, disrupts sleep and leads to psychiatric complications such as comorbid anxiety and depression. The management is palliative and involves drugs, psychological intervention, stimulations and nerve-blocking techniques. This review concentrates on the pharmacological therapeutic options available and focuses on the selection of the agent/s in accordance with the evidence. The first-line treatment includes the tricyclic antidepressants ([TCAs]; amitriptyline, nortriptyline, selective serotonin norepinephrine inhibitors ([SNRIs]; duloxetine, venlafaxine, calcium channel alpha 2 - delta ligands (pregabalin, gabapentin, carbamazepine and oxcarbazepine. Lidocaine plasters are first-line options for specific focal conditions such as post-herpetic neuralgia. The second-line therapy includes the opioid analgesics and tramadol. The choice of drug selection should complement the patient’s age, type of neuropathic condition, tolerability to an agent, comorbid condition and cost-effectiveness. Management must be individualized with a realistic and composite goal of making the pain tolerable and

  3. Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain.

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    Ren, Zhenyu; Yang, Bing; Yang, Bin; Shi, Le; Sun, Qing-Li; Sun, A-Ping; Lu, Lin; Liu, Xiaoguang; Zhao, Rongsheng; Zhai, Suodi

    2015-11-01

    Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.

  4. Sodium hydrosulfide relieves neuropathic pain in chronic constriction injured rats.

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    Lin, Jian-Qing; Luo, Hui-Qin; Lin, Cai-Zhu; Chen, Jin-Zhuan; Lin, Xian-Zhong

    2014-01-01

    Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP). Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS) could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI) were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S). The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL), mechanical withdrawal threshold (MWT), and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05). NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

  5. Sodium Hydrosulfide Relieves Neuropathic Pain in Chronic Constriction Injured Rats

    Directory of Open Access Journals (Sweden)

    Jian-qing Lin

    2014-01-01

    Full Text Available Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain (NPP. Channel protein pCREB of that activity has been shown to mitigate the onset of associated molecular events in the nervous system, and sodium hydrosulfide (NaHS could inhibit the expression of pCREB. However, whether NaHS could relieve the pain, it needs further experimental research. Furthermore, the clinical potential that NaHS was used to relieve pain was limited so it would be required. To address these issues, the rats of sciatic nerve chronic constriction injury (CCI were given intraperitoneal injection of NaHS containing hydrogen sulfide (H2S. The experimental results showed that NaHS inhibited the reduction of paw withdrawal thermal latency (PWTL, mechanical withdrawal threshold (MWT, and the level of pCREB in CCI rats in a dose-dependent manner and they were greatly decreased in NaHSM group (P < 0.05. NaHS alleviates chronic neuropathic pain by inhibiting expression of pCREB in the spinal cord of Sprague-Dawley rats.

  6. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats.

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    Zheng Li

    Full Text Available BACKGROUND: Chronicity of pain is one of the most interesting questions in chronic pain study. Clinical and experimental data suggest that supraspinal areas responsible for negative emotions such as depression and anxiety contribute to the chronicity of pain. The amygdala is suspected to be a potential structure for the pain chronicity due to its critical role in processing negative emotions and pain information. OBJECTIVE: This study aimed to investigate whether amygdala or its subregions, the basolateral amygdala (BLA and the central medial amygdala (CeA, contributes to the pain chronicity in the spared nerve injury (SNI-induced neuropathic pain model of rats. METHODOLOGY/PRINCIPAL FINDINGS: (1 Before the establishment of the SNI-induced neuropathic pain model of rats, lesion of the amygdaloid complex with stereotaxic injection of ibotenic acid (IBO alleviated mechanical allodynia significantly at days 7 and 14, even no mechanical allodynia at day 28 after SNI; Lesion of the BLA, but not the CeA had similar effects; (2 however, 7 days after SNI when the neuropathic pain model was established, lesion of the amygdala complex or the BLA or the CeA, mechanical allodynia was not affected. CONCLUSION: These results suggest that BLA activities in the early stage after nerve injury might be crucial to the development of pain chronicity, and amygdala-related negative emotions and pain-related memories could promote pain chronicity.

  7. Chronic neuropathic pain: mechanisms, drug targets and measurement

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    Finnerup, Nanna Brix; Sindrup, Søren H.; Jensen, Troels Staehelin

    2007-01-01

    Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. Precli...... assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials.......Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems...

  8. The oxidative response in the chronic constriction injury model of neuropathic pain.

    NARCIS (Netherlands)

    Tan, E.C.T.H.; Bahrami, S.; Kozlov, A.V.; Kurvers, H.A.J.M.; Laak, H.J. ter; Nohl, H.; Redl, H.; Goris, R.J.A.

    2009-01-01

    BACKGROUND: In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model obse

  9. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain

    OpenAIRE

    Jeanmonod, D.; Werner, B.; Morel, A.; Michels, L; Zadicario, E; Schiff, G.; Martin, E.

    2012-01-01

    Object Recent technological developments open the field of therapeutic application of focused ultrasound to the brain through the intact cranium. The goal of this study was to apply the new transcranial magnetic resonance imaging-guided focused ultrasound (tcMRgFUS) technology to perform noninvasive central lateral thalamotomies (CLTs) as a treatment for chronic neuropathic pain. Methods In 12 patients suffering from chronic therapy-resistant neuropathic pain, tcMRgFUS CLT was propos...

  10. A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls

    DEFF Research Database (Denmark)

    Baastrup, Sidsel; Schultz, Rikke; Moore, Rod;

    2016-01-01

    different groups of chronic pain patients and a group of healthy controls. Thirty neuropathic pain (NP) patients, 28 fibromyalgia (FM) patients, and 26 pain-free healthy controls completed the Coping Strategy Questionnaire (CSQ-48/27) and rated their daily pain. The results showed that FM and NP patients...

  11. Is the pain in chronic pancreatitis of neuropathic origin? Support from EEG studies during experimental pain

    Institute of Scientific and Technical Information of China (English)

    Asbjφrn M Drewes; Maciej Gratkowski; Saber AK Sami; Georg Dimcevski; Peter Funch-Jensen; Lars Arendt-Nielsen

    2008-01-01

    AIM: To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation.METHODS: Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and "topographic matching pursuit" was used to extract the EEG information in the early brain activation after stimulation.RESULTS: A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation between the channels. The main theta components oscillated with 4.4Hz in the patients and 5.5Hz in the controls. The energy in the delta (0.5-3.5Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band.CONCLUSION: The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.

  12. Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain

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    Calenbergh, F. Van; Gybels, J.; Laere, K. Van;

    2009-01-01

    BACKGROUND: Chronic neuropathic pain after injury to a peripheral nerve is known to be resistant to treatment. Peripheral nerve stimulation is one of the possible treatment options, which is, however, not performed frequently. In recent years we have witnessed a renewed interest for PNS. The aim...... of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...... functioning) also showed positive effects. Quantitative Sensory Testing results did not show significant differences in cold pain and heat pain thresholds between the "ON" and "OFF" conditions. CONCLUSION: In selected patients with peripheral neuropathic pain PNS remains effective even after more than 20...

  13. Increased miR-132-3p expression is associated with chronic neuropathic pain.

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    Leinders, M; Üçeyler, N; Pritchard, R A; Sommer, C; Sorkin, L S

    2016-09-01

    Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (panimal model of neuropathic pain, the spared nerve injury model (SNI). For this purpose miR-132-3p expression levels were measured in dorsal root ganglia and spinal cord of rats. Subsequently, miR-132-3p expression was pharmacologically modulated with miRNA antagonists or mimetics, and evoked pain and pain aversion were assessed. Spinal miR-132-3p levels were highest 10days after SNI, a time when persistent allodynia was established (pbehavior in the place escape avoidance paradigm (pbehavior in naïve rats (p<0.001). Taken together these results indicate a pro-nociceptive effect of miR-132-3p in chronic neuropathic pain. PMID:27349406

  14. An improved behavioural assay demonstrates that ultrasound vocalizations constitute a reliable indicator of chronic cancer pain and neuropathic pain

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    Selvaraj Deepitha

    2010-03-01

    Full Text Available Abstract Background On-going pain is one of the most debilitating symptoms associated with a variety of chronic pain disorders. An understanding of mechanisms underlying on-going pain, i.e. stimulus-independent pain has been hampered so far by a lack of behavioural parameters which enable studying it in experimental animals. Ultrasound vocalizations (USVs have been proposed to correlate with pain evoked by an acute activation of nociceptors. However, literature on the utility of USVs as an indicator of chronic pain is very controversial. A majority of these inconsistencies arise from parameters confounding behavioural experiments, which include novelty, fear and stress due to restrain, amongst others. Results We have developed an improved assay which overcomes these confounding factors and enables studying USVs in freely moving mice repetitively over several weeks. Using this improved assay, we report here that USVs increase significantly in mice with bone metastases-induced cancer pain or neuropathic pain for several weeks, in comparison to sham-treated mice. Importantly, analgesic drugs which are known to alleviate tumour pain or neuropathic pain in human patients significantly reduce USVs as well as mechanical allodynia in corresponding mouse models. Conclusions We show that studying USVs and mechanical allodynia in the same cohort of mice enables comparing the temporal progression of on-going pain (i.e. stimulus-independent pain and stimulus-evoked pain in these clinically highly-relevant forms of chronic pain.

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

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    GURPREET KAUR

    2015-03-01

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

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

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    Kaur, Gurpreet; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar S

    2015-03-01

    The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress) and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o.) and its saponin rich fraction (100 and 200 mg/kg p.o.) for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels. PMID:25673470

  17. Virtual reality hypnosis in the treatment of chronic neuropathic pain: a case report.

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    Oneal, Brent J; Patterson, David R; Soltani, Maryam; Teeley, Aubriana; Jensen, Mark P

    2008-10-01

    This case report evaluates virtual reality hypnosis (VRH) in treating chronic neuropathic pain in a patient with a 5-year history of failed treatments. The patient participated in a 6-month trial of VRH, and her pain ratings of intensity and unpleasantness dropped on average 36% and 33%, respectively, over the course of 33 sessions. In addition, she reported both no pain and a reduction of pain for an average of 3.86 and 12.21 hours, respectively, after treatment sessions throughout the course of the VRH treatment. These reductions and the duration of treatment effects following VRH treatment were superior to those following a trial of standard hypnosis (non-VR) treatment. However, the pain reductions with VRH did not persist over long periods of time. The findings support the potential of VRH treatment for helping individuals with refractory chronic pain conditions. PMID:18726807

  18. Cognitive behavioural treatment programme for chronic neuropathic pain after spinal cord injury

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    Heutink, M.

    2014-01-01

    People with spinal cord injury (SCI) often face serious secondary health conditions, including different types of pain. Neuropathic pain is often rated by them as the most severe type of pain. Pharmacological interventions are often insufficiently effective in providing neuropathic pain relief and,

  19. Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society

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    Moulin, DE; Boulanger, A; AJ Clark; Clarke, H.; Dao, T; GA Finley; Furlan, A.; Gilron, I; Gordon, A.; PK Morley-Forster; BJ Sessle; Squire, P; Stinson, J; Taenzer, P.; Velly, A

    2014-01-01

    BACKGROUND: Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians. OBJECTIVE: To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management. METHODS: RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP ...

  20. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

    DEFF Research Database (Denmark)

    Amris, Kirstine; Jespersen, Anders; Bliddal, Henning

    2010-01-01

    Widespread pain and pain hypersensitivity are the hallmark of fibromyalgia, a complex pain condition linked to central sensitization. In this study the painDETECT questionnaire (PDQ), validated to identify neuropathic pain and based on pain quality items, was applied in a cross-sectional sample...... of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP...... examination was conducted according to ACR guidelines. Computerized cuff pressure algometry was used for the assessment of pressure-pain detection thresholds (PDT, unit: kPa) and pressure-pain tolerance thresholds (PTT, unit: kPa). Mean TP count was 14.32 (range: 2-18), mean PDQ score 22.75 (range: 5...

  1. A Case of Chronic Abdominal Neuropathic Pain and Burning after Female Genital Cutting.

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    Hadid, Vicky; Dahan, Michael Haim

    2015-01-01

    Introduction. Female genital cutting is prevalent in the Middle Eastern and African countries. This ritual entails not only immediate complications such as infection, pain, and haemorrhage, but also chronic ones including dysmenorrhea and dyspareunia. However, there is limited data on neuropathic pain secondary to female genital mutilation when searching the literature. Case. This case discusses a 38-year-old female with a history of infibulation who presented with a chronic burning abdominal and anterior vulvar pain including the related investigations and treatment. Discussion. This case brings to light the additional delayed complication of this ritual: sensory neuropathy. Our goal is to educate health professionals to be aware of these complications and to appropriately investigate and treat them in order to find a solution to relieve the patients' symptoms. PMID:26137334

  2. A Case of Chronic Abdominal Neuropathic Pain and Burning after Female Genital Cutting

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    Vicky Hadid

    2015-01-01

    Full Text Available Introduction. Female genital cutting is prevalent in the Middle Eastern and African countries. This ritual entails not only immediate complications such as infection, pain, and haemorrhage, but also chronic ones including dysmenorrhea and dyspareunia. However, there is limited data on neuropathic pain secondary to female genital mutilation when searching the literature. Case. This case discusses a 38-year-old female with a history of infibulation who presented with a chronic burning abdominal and anterior vulvar pain including the related investigations and treatment. Discussion. This case brings to light the additional delayed complication of this ritual: sensory neuropathy. Our goal is to educate health professionals to be aware of these complications and to appropriately investigate and treat them in order to find a solution to relieve the patients’ symptoms.

  3. Neuropathic pain in children.

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    Howard, Richard F; Wiener, Suzanne; Walker, Suellen M

    2014-01-01

    Neuropathic pain (NP), due to a lesion or disease of the somatosensory nervous system, is not well documented or researched in children. NP is a clinical diagnosis that can be difficult, especially in younger children. Nevertheless, it is important to recognise NP, as pain mechanisms and consequently management and prognosis differ from other types of long-term pain. NP is common in adult pain clinics but many of the underlying disease states in which it occurs are infrequently or never encountered in paediatric practice. However, NP in childhood has been reported, even in the very young in certain clinical situations. Causes of NP include traumatic injury, complex regional pain syndrome type II, cancer and chemotherapy, chronic infection, neurological and metabolic disease, and inherited sensory nerve dysfunction. The clinical and laboratory study of traumatic peripheral nerve injury has revealed important age-related differences in clinical presentation and prognosis. It is clear that mechanisms operating during development can profoundly modify the consequences of nerve damage and NP. Clinically, diagnosis, assessment and treatment of NP are based on methods and evidence derived from data in adults. Improvements in the understanding and management of NP are likely to come from developmentally appropriate improvements in the clarity and consistency of diagnosis and systematic, well-researched approaches to treatment.

  4. Parents' perspective of their journey caring for a child with chronic neuropathic pain.

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    Gaughan, Veronica; Logan, Deirdre; Sethna, Navil; Mott, Sandra

    2014-03-01

    When a child has chronic pain, it affects the parents. Their response and how it is factored into their lives and family function was the phenomenon of interest that drove this study. The available literature was sparse, especially when the pain etiology was neuropathic. The purpose of this study was to describe the parents' perception of the pain journey from the initial occurrence of their child's pain through the labyrinth of treatment options to successful outcome, to gain a better understanding of parental beliefs about pain, and to learn how parental attitudes and behaviors relate to children's response to treatment for chronic pain. Qualitative descriptive design was used to better understand the phenomenon from those who were the experts because they had experienced it. Parents whose child was enrolled in a pain rehabilitation program participated in open-ended interviews. The children/adolescents were 8-18 years old and diagnosed with complex regional pain syndrome or a related chronic pain condition. During data immersion, the investigators uncovered the pervasive underlying themes of suffering and disempowerment. In addition, the multiple meaning elements were grouped into three categories and supportive subcategories labeled as follows: parent distress, with subcategories schism in parenting, searching, and disabled parenting; and lack of control, with the subcategories family/community, fear, and empowerment. The voices of parents were heard in their description of the exhausting and difficult journey in search of pain relief for their child. Their comments provided insight into how they defined the child's pain and their related parental role.

  5. Parents' perspective of their journey caring for a child with chronic neuropathic pain.

    Science.gov (United States)

    Gaughan, Veronica; Logan, Deirdre; Sethna, Navil; Mott, Sandra

    2014-03-01

    When a child has chronic pain, it affects the parents. Their response and how it is factored into their lives and family function was the phenomenon of interest that drove this study. The available literature was sparse, especially when the pain etiology was neuropathic. The purpose of this study was to describe the parents' perception of the pain journey from the initial occurrence of their child's pain through the labyrinth of treatment options to successful outcome, to gain a better understanding of parental beliefs about pain, and to learn how parental attitudes and behaviors relate to children's response to treatment for chronic pain. Qualitative descriptive design was used to better understand the phenomenon from those who were the experts because they had experienced it. Parents whose child was enrolled in a pain rehabilitation program participated in open-ended interviews. The children/adolescents were 8-18 years old and diagnosed with complex regional pain syndrome or a related chronic pain condition. During data immersion, the investigators uncovered the pervasive underlying themes of suffering and disempowerment. In addition, the multiple meaning elements were grouped into three categories and supportive subcategories labeled as follows: parent distress, with subcategories schism in parenting, searching, and disabled parenting; and lack of control, with the subcategories family/community, fear, and empowerment. The voices of parents were heard in their description of the exhausting and difficult journey in search of pain relief for their child. Their comments provided insight into how they defined the child's pain and their related parental role. PMID:23219393

  6. Targeting the affective and cognitive aspects of chronic neuropathic pain using basal forebrain neuromodulation: rationale, review and proposal.

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    Oluigbo, Chima O; Salma, Asem; Rezai, Ali R

    2012-09-01

    Chronic pain is a major health problem in developed countries where it may affect as much as 20% of the adult population. There have been no significant clinical breakthroughs in therapeutic options for persons with chronic neuropathic pain. These limitations underscore the importance of developing new therapies for this disabling pain syndrome. We have reviewed the limitations of the present treatment strategies for chronic pain, neurophysiology of somatosensory transmission and nociception, mechanisms of neuropathic pain, the concept of a "pain matrix" and the "top-down" modulation of pain, and the cognitive affective role in processing of the pain experience. We found that affective and cognitive aspects of pain constitute important considerations in achieving improvements in the outcomes of pain neuromodulation in patients with chronic neuropathic pain. Based on our review, we propose that future novel neuromodulatory therapeutic strategies should be directed at areas in the brain that are involved in the neural mechanisms of reward valuation and appetitive motivation such as nucleus accumbens, ventral tegmental area, and prefrontal cortex.

  7. Long term treatment with gabapentin in an animal model of chronic neuropathic pain

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    Baastrup, C. S.; Andrews, N.; Wegener, Gregers;

    2013-01-01

    In preclinical animal pain research potential efficacy of a drug is often evaluate after a single exposure, which is in contrast to the long lasting treatment needed in chronic neuropathic pain (CNP) patients. Gabapentin remains one of the most efficacious drugs in the treatment of CNP. The aims...... of the study were to evaluate the spinal cord contusion (SCC) model and 2 different measures of painlike behaviour using a long term treatment schedule with gabapentin. Furthermore the effect on mobility and on anxiety, a pain-related behaviour, was included. 40 Female SD rats with a T13 SCC and sham animals....... Daily treatment with gabapentin 30 mg/kg sc. or saline for 6 consecutive weeks. Mechanical sensitivity thresholds (MST) to von Frey stimulation of hindpaws and thorax measured by both reflex withdrawal and supra-spinal responses. Anxiety-like behaviour using the openfield paradigm. Drug effect...

  8. Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report

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    Sørensen, Jens Christian Hedemann; Meier, Kaare; Perinpam, Larshan;

    Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report......Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report...

  9. Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Wiesenfeld-Hallin Zsuzsanna

    2009-02-01

    Full Text Available Abstract Background Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4 DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. Results In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na+ channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the "uninjured" L4DRG showed altered expression (24 ± 28. Conclusion Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger "look-up table" of genes whose

  10. An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain.

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    Lucy H R Whitaker

    Full Text Available Chronic pelvic pain (CPP affects 5.7-26.6% women worldwide. 55% have no obvious pathology and 40% have associated endometriosis. Neuropathic pain (NeP is pain arising as a consequence of a lesion/disease affecting the somatosensory system. The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is challenging because there is no gold-standard assessment. Questionnaires have been used in the clinical setting to diagnose NeP in other chronic pain conditions and quantitative sensory testing (QST has been used in a research setting to identify abnormal sensory function. We aimed to determine if women with chronic pelvic pain (CPP have a neuropathic pain (NeP component to their painful symptoms and how this is best assessed. We performed an exploratory prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They underwent a clinician completed questionnaire (DN4 and completed the S-LANSS and PainDETECT™ questionnaires. Additionally QST testing was performed by a clinician. They also completed a patient acceptability questionnaire. Clinical features of NeP were identified by both questionnaires and QST. Of the women who were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and PainDETECT™ respectively. When NeP was identified by questionnaire, the associated laparoscopy findings were similar irrespective of which questionnaire was used. No subject had entirely unchanged QST parameters. There were distinct loss and gain subgroups, as well as mixed alteration in function, but this was not necessarily clinically significant in all patients. 80% of patients were confident that questionnaires could diagnose NeP, and 90% found them easy to complete. Early identification of NeP in women with CPP with a simple questionnaire could facilitate targeted therapy with neuromodulators, which are cheap, readily available, and have good safety profiles. This approach could prevent unnecessary or fertility

  11. An Exploratory Study into Objective and Reported Characteristics of Neuropathic Pain in Women with Chronic Pelvic Pain

    Science.gov (United States)

    Whitaker, Lucy H. R.; Reid, Jen; Choa, Alex; McFee, Stuart; Seretny, Marta; Wilson, John; Elton, Rob A.; Vincent, Katy; Horne, Andrew W.

    2016-01-01

    Chronic pelvic pain (CPP) affects 5.7–26.6% women worldwide. 55% have no obvious pathology and 40% have associated endometriosis. Neuropathic pain (NeP) is pain arising as a consequence of a lesion/disease affecting the somatosensory system. The prevalence of NeP in women with CPP is not known. The diagnosis of NeP is challenging because there is no gold-standard assessment. Questionnaires have been used in the clinical setting to diagnose NeP in other chronic pain conditions and quantitative sensory testing (QST) has been used in a research setting to identify abnormal sensory function. We aimed to determine if women with chronic pelvic pain (CPP) have a neuropathic pain (NeP) component to their painful symptoms and how this is best assessed. We performed an exploratory prospective cohort study of 72 pre-menopausal women with a diagnosis of CPP. They underwent a clinician completed questionnaire (DN4) and completed the S-LANSS and PainDETECT™ questionnaires. Additionally QST testing was performed by a clinician. They also completed a patient acceptability questionnaire. Clinical features of NeP were identified by both questionnaires and QST. Of the women who were NeP positive, 56%, 35% and 26% were identified by the S-LANSS, DN4 and PainDETECT™ respectively. When NeP was identified by questionnaire, the associated laparoscopy findings were similar irrespective of which questionnaire was used. No subject had entirely unchanged QST parameters. There were distinct loss and gain subgroups, as well as mixed alteration in function, but this was not necessarily clinically significant in all patients. 80% of patients were confident that questionnaires could diagnose NeP, and 90% found them easy to complete. Early identification of NeP in women with CPP with a simple questionnaire could facilitate targeted therapy with neuromodulators, which are cheap, readily available, and have good safety profiles. This approach could prevent unnecessary or fertility

  12. Moringa oleifera Leaves Extract Attenuates Neuropathic Pain Induced by Chronic Constriction Injury

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    Jurairat Khongrum

    2012-01-01

    Full Text Available Problem statement: Neuropathic pain, a challenge of this decade, has been reported to be associated with the diversity conditions including diabetes. At present, there are no conventional analgesics that can effectively treat neuropathic pain with a satisfactory outcome. Due to the limitation of therapeutic efficacy, the searching for novel effective remedies in the management of neuropathic pain is required. Approach: Male Wistar rats, weighing 180-220 g were induced diabetes mellitus by Streptozotocin (STZ (single injection, 65 mg kg-1 BW, i.p. Diabetic rats were induced neuropathic pain by Constricting the right sciatic nerve (CCI at permanently. Then, all rats were administered the extract of M. oleifera leaves at doses of 100, 200 and 300 mg kg-1 BW once daily in a period of 21 days. The analgesic effect of the plant extract was evaluated using Von Frey filament and hot plate tests every 3 days after CCI throughout 21-day experimental period. In addition, at the end of the experiment, the alteration of oxidative damage markers including MDA level and the activities of SOD, CAT and GSH-PX in the injured sciatic nerve were also evaluated. Results: The current results showed that rats subjected to M.oleifera leaves extract at doses of 100 and 200 mg kg-1 BW significantly reversed the decreased withdrawal threshold intensity and withdrawal latency in Von Frey filament and hot plate tests respectively. In addition, rats subjected to the medium dose extract also reversed the decreased activities of SOD and GSH-Px and the elevation of MDA level in the injured nerve. Taken all together, our data suggest that M. oleifera leaves extract can attenuate neuropathic pain in diabetic condition. The possible underlying mechanism may occur partly via the decreased oxidative stress. However, other mechanisms may also involve. Conclusion: Our results suggest that M. oleifera leaves may be the potential novel adjuvant therapy for neuropathic pain management.

  13. Functional and metabolic changes in the brain in neuropathic pain syndrome against the background of chronic epidural electrostimulation of the spinal cord.

    Science.gov (United States)

    Sufianov, A A; Shapkin, A G; Sufianova, G Z; Elishev, V G; Barashin, D A; Berdichevskii, V B; Churkin, S V

    2014-08-01

    Changes in functional and metabolic activities of the brain were evaluated by EEG and positron-emission/computer tomography with 18F-fluorodeoxyglucose in patients with neuropathic pain syndrome previous to and 3 months after implantation of a system for chronic epidural spinal cord stimulation. In most cases, the use of a nerve stimulator was followed by alleviation of neuropathic pain and partial normalization of functional and metabolic activities of brain structures responsible for pain perception, emotiogenic, behavioral, and autonomic responses.

  14. Self-reported somatosensory symptoms of neuropathic pain in fibromyalgia and chronic widespread pain correlate with tender point count and pressure-pain thresholds

    DEFF Research Database (Denmark)

    Amris, Kirstine; Jespersen, Anders; Bliddal, Henning

    2010-01-01

    of patients with chronic widespread pain (CWP). The aims of the study were to assess the patient-reported sensory neuropathic symptoms by PDQ and to correlate these with tender point (TP) count and pressure-pain thresholds. Eighty-one patients (75 F, 6 M) with CWP (ACR-criteria) filled in the PDQ. Manual TP......-37). Mean PDT was 8.8 kPa (range: 2-36) and mean PTT 30.9 kPa (range: 4-85). Deep-tissue hyperalgesia was the predominant somatosensory symptom reported in 83%, but other neuropathic symptoms were also frequent, e.g. burning 51% and prickling 47%. Statistically significant correlations were found between...

  15. Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

    OpenAIRE

    Venkata R.K. Thiagarajan; Palanichamy Shanmugam; Uma M. Krishnan; Arunachalam Muthuraman; Nirmal Singh

    2012-01-01

    The present study was designed to investigate the ameliorative role of ethanolic extract from leaves of Butea monosperma in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia & allodynia in the left hind paw and tail thermal hyperalgesia. Further on, thiobarbituric acid reac...

  16. The Effect of Verbascoside in Neuropathic Pain Induced by Chronic Constriction Injury in Rats.

    Science.gov (United States)

    Amin, Bahareh; Poureshagh, Ehsan; Hosseinzadeh, Hossein

    2016-01-01

    We examined the effects of verbascoside in rats subjected to chronic constriction injury (CCI). Verbascoside (50, 100, and 200 mg/kg, i.p.), was administered from the day of surgery for 14 days. Spinal cord levels of apoptotic factors and glia markers were quantified on days 3, 7, and 14 post-CCI. Oxidative stress markers were assessed on days 7 and 14. CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. A significant increase in the levels of Iba (a marker of microglia activation) and Bax (a proapoptotic factor) was observed on day 3. Iba remained high on day 7. In contrast, there were no differences in glial fibrillary acidic protein contents between sham and CCI animals. Malondialdehyde increased and reduced glutathione decreased on day 14. Verbascoside significantly attenuated behavioral changes associated with neuropathy. Bax decreased, while Bcl-2 was increased by verbascoside on day 3. Verbascoside also reduced Iba protein on days 3 and 7. The results support evidence that microglial activation, apoptotic factors, and oxidative stress may have a pivotal role in the neuropathic pain pathogenesis. It is suggested that antinociceptive effects elicited by verbascoside might be through the inhibition of microglia activation, apoptotic pathways, and antioxidant properties. PMID:26537351

  17. Neuropathic pain therapy: from bench to bedside.

    Science.gov (United States)

    Backonja, Miroslav Misha

    2012-07-01

    Neuropathic pain is a result of complex interactions between peripheral and central mechanisms with multiple potential therapeutic targets. However, the complexity of these mechanisms and relative youth of translational pain research, which is in its infancy, have prevented translation of successful basic bench research to human therapy. Most of the clinically available neuropathic pain treatments are borrowed from other therapeutic areas, such as antidepressants and antiepileptics, or involve application of older therapy, such as opioids. Exceptions are ziconotide, tapentadol, and the high-concentration capsaicin patch. Similar to all other analgesic agents, these provide only partial pain relief in subsets of patients. The standard of care for patients with chronic neuropathic pain is multimodal and multidisciplinary. For most patients to achieve and maintain satisfactory pain relief a combination of therapeutic agents is necessary, providing the empiric basis for rational polypharmacy, which has become a standard approach as well. PMID:23117951

  18. Advances in brain imaging of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    CHEN Fu-yong; TAO Wei; LI Yong-jie

    2008-01-01

    Objective To review the literature on the use of brain imaging,including functional magnetic resonance imaging(fMRI), positron emission tomography(PET),magnetic resonance spectroscopy(MRS)and voxel-based morphometry(VBM)in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain. Data sources English literatures from January 1,2000 to July 31,2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM,using PET,fMRI,VBM,MRS and receptor binding. Study selection Published articles about the application of fMRI,PET,VBM,MRS and chronic neuropathic pain were selected. Data extraction Data were mainly extracted from 40 representative articles as the research basis. Results The PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia.The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain,which is not seen in a matched control group.However,the results obtained had a large variety,which may be due to different pain etiology,pain distribution,lesion tomography,symptoms and stimulation procedures. Conclusions Application of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization In patients with neuropathic pain.However,a unique"pain matrix" has not been defined.Future studies should be conducted using a prospective longitudinal research design,which would guarantee the control for many confounding factors.

  19. Feasibility of Human Amniotic Fluid Derived Stem Cells in Alleviation of Neuropathic Pain in Chronic Constrictive Injury Nerve Model.

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    Chien-Yi Chiang

    Full Text Available The neurobehavior of neuropathic pain by chronic constriction injury (CCI of sciatic nerve is very similar to that in humans, and it is accompanied by a profound local inflammation response. In this study, we assess the potentiality of human amniotic fluid derived mesenchymal stem cells (hAFMSCs for alleviating the neuropathic pain in a chronic constriction nerve injury model.This neuropathic pain animal model was conducted by four 3-0 chromic gut ligatures loosely ligated around the left sciatic nerve in Sprague-Dawley rats. The intravenous administration of hAFMSCs with 5x105 cells was conducted for three consecutive days.The expression IL-1β, TNF-α and synaptophysin in dorsal root ganglion cell culture was remarkably attenuated when co-cultured with hAFMSCs. The significant decrease of PGP 9.5 in the skin after CCI was restored by administration of hAFMSCs. Remarkably increased expression of CD 68 and TNF-α and decreased S-100 and neurofilament expression in injured nerve were rescued by hAFMSCs administration. Increases in synaptophysin and TNF-α over the dorsal root ganglion were attenuated by hAFMSCs. Significant expression of TNF-α and OX-42 over the dorsal spinal cord was substantially attenuated by hAFMSCs. The increased amplitude of sensory evoked potential as well as expression of synaptophysin and TNF-α expression was alleviated by hAFMSCs. Human AFMSCs significantly improved the threshold of mechanical allodynia and thermal hyperalgesia as well as various parameters of CatWalk XT gait analysis.Human AFMSCs administration could alleviate the neuropathic pain demonstrated in histomorphological alteration and neurobehavior possibly through the modulation of the inflammatory response.

  20. p300 exerts an epigenetic role in chronic neuropathic pain through its acetyltransferase activity in rats following chronic constriction injury (CCI

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    Zhu Xiao-Yan

    2012-11-01

    Full Text Available Abstract Background Neuropathic pain is detrimental to human health; however, its pathogenesis still remains largely unknown. Overexpression of pain-associated genes and increased nociceptive somato-sensitivity are well observed in neuropathic pain. The importance of epigenetic mechanisms in regulating the expression of pro- or anti-nociceptive genes has been revealed by studies recently, and we hypothesize that the transcriptional coactivator and the histone acetyltransferase E1A binding protein p300 (p300, as a part of the epigenetic mechanisms of gene regulation, may be involved in the pathogenesis of neuropathic pain induced by chronic constriction injury (CCI. To test this hypothesis, two different approaches were used in this study: (I down-regulating p300 with specific small hairpin RNA (shRNA and (II chemical inhibition of p300 acetyltransferase activity by a small molecule inhibitor, C646. Results Using the CCI rat model, we found that the p300 expression was increased in the lumbar spinal cord on day 14 after CCI. The treatment with intrathecal p300 shRNA reversed CCI-induced mechanical allodynia and thermal hyperalgesia, and suppressed the expression of cyclooxygenase-2 (COX-2, a neuropathic pain-associated factor. Furthermore, C646, an inhibitor of p300 acetyltransferase, also attenuated mechanical allodynia and thermal hyperalgesia, accompanied by a suppressed COX-2 expression, in the spinal cord. Conclusions The results suggest that, through its acetyltransferase activity in the spinal cord after CCI, p300 epigenetically plays an important role in neuropathic pain. Inhibiting p300, using interfering RNA or C646, may be a promising approach to the development of new neuropathic pain therapies.

  1. Identification of discrete sites of action of chronic treatment with desipramine in a model of neuropathic pain.

    Science.gov (United States)

    Jones, K L; Finn, D P; Governo, R J M; Prior, M J; Morris, P G; Kendall, D A; Marsden, C A; Chapman, V

    2009-02-01

    Tricyclic antidepressants (TCAs) are an important analgesic treatment for neuropathic pain, though the neural substrates mediating these effects are poorly understood. We have used an integrative approach combining behavioural pharmacology with functional magnetic resonance imaging (fMRI) to investigate the effects of chronic treatment with the TCA desipramine, on touch-evoked pain (mechanical allodynia) and brain regional activity in the selective spinal nerve ligation (SNL) model of neuropathic pain. SNL and sham-operated rats received once daily i.p. administration of 10 mg/kg DMI, or saline, for 14 days. Withdrawal responses to the application of a normally non-noxious (10 g) stimulus were recorded in SNL and sham-operated rats over this period. On the final day of the study, SNL and sham-operated rats received a final challenge dose of DMI (10 mg/kg i.p.) during fMRI scanning. Chronic administration of desipramine (DMI) significantly attenuated mechancial allodynia in SNL rats. DMI challenge in chronic DMI-treated neuropathic rats produced significantly greater activation of the deep mesencephalic nucleus, primary somatosensory cortex, insular cortex, medial globus pallidus, inferior colliculus, perirhinal cortex and cerebellum compared to sham-operated rats and saline controls. By contrast, the spatial pattern of brain regional activation by chronic DMI treatment in sham controls encompassed a number of other areas including those associated with learning and memory processes. These novel findings identify key brain regions implicated in the analgesic and mood altering effects associated with chronic treatment with DMI.

  2. Neuropathic pain management in children.

    LENUS (Irish Health Repository)

    Hyde, Catherine

    2012-10-01

    There are difficulties in assessing, managing, and evaluating neuropathic pain in dying children, particularly those with neurological impairment. Neuropathic pain in children often presents differently to how it presents in the adult population. Comprehensive assessment as well as pharmacological and non-pharmacological interventions are crucial to its successful management and frequently require input from an interdisciplinary team. Notwithstanding the need for further research, this paper brings together research papers, reviews, and clinical guidelines to present an exploration of existing evidence regarding care for children with neuropathic pain and their families.

  3. [Challenges in the treatment of neuropathic pain].

    Science.gov (United States)

    Teixeira, Manoel Jacobsen

    2009-10-01

    Neuropathic pain is a difficult to diagnose condition. The definition changes have tried to clarify the confusing consequences about including the word "dysfunction". However, diagnosing problems are not only a definition issue, but also a technical problem. Heat-pulsing-lasers are a very interesting tool to diagnose neuropathic pain, but, at the moment, they are not available in many clinical centers. Because there was not a precise diagnostic tool widely available, a gradation system was developed. It classifies neuropathic pain into three categories: definite, probable or possible neuropathic pain. Neuropathic pain can be produced by different lesions or diseases, either in the central nervous system (CNS) or in the peripheral nervous system (PNS), and it uses to appear in a context of some comorbidities, so it is important to determine the impact over the quality of life and also over the economy (chronic treatment and sick leaves). Some studies have tried to estimate these consequences. Pregabalin has provided throughout different studies important health system cost reductions and also reduced sick leaves. Nevertheless, because only pharmacological-based therapies cannot control disease symptoms and there are still diagnostic problems, it is important to perform a multidisciplinary approach to neuropathic pain to balance these issues. Thus, some studies have investigated different non-pharmacological approaches to treat neuropathic pain, such as intensive exercise, hydrotherapy, transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation, motor imagery programs (MIP), supportive psychotherapy, and cognitive behavior therapy. To perform these non-pharmacological therapies, a multidisciplinary team focused on individualizing pain management is needed. PMID:20087479

  4. A multidisciplinary cognitive behavioural programme for coping with chronic neuropathic pain following spinal cord injury: the protocol of the CONECSI trial

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    Dijkstra Catja A

    2010-10-01

    Full Text Available Abstract Background Most people with a spinal cord injury rate neuropathic pain as one of the most difficult problems to manage and there are no medical treatments that provide satisfactory pain relief in most people. Furthermore, psychosocial factors have been considered in the maintenance and aggravation of neuropathic spinal cord injury pain. Psychological interventions to support people with spinal cord injury to deal with neuropathic pain, however, are sparse. The primary aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain trial is to evaluate the effects of a multidisciplinary cognitive behavioural treatment programme on pain intensity and pain-related disability, and secondary on mood, participation in activities, and life satisfaction. Methods/Design CONECSI is a multicentre randomised controlled trial. A sample of 60 persons with chronic neuropathic spinal cord injury pain will be recruited from four rehabilitation centres and randomised to an intervention group or a waiting list control group. The control group will be invited for the programme six months after the intervention group. Main inclusion criteria are: having chronic (> 6 months neuropathic spinal cord injury pain as the worst pain complaint and rating the pain intensity in the last week as 40 or more on a 0-100 scale. The intervention consists of educational, cognitive, and behavioural elements and encompasses 11 sessions over a 3-month period. Each meeting will be supervised by a local psychologist and physical therapist. Measurements will be perfomed before starting the programme/entering the control group, and at 3, 6, 9, and 12 months. Primary outcomes are pain intensity and pain-related disability (Chronic Pain Grade questionnaire. Secondary outcomes are mood (Hospital Anxiety and Depression Scale, participation in activities (Utrecht Activities List, and life satisfaction (Life Satisfaction Questionnaire. Pain coping and pain cognitions will be

  5. Use of Methadone for Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Dwight Moulin

    2003-01-01

    Full Text Available Chronic neuropathic pain is often considered to be a common complication of injury to the central or peripheral nervous system and the pain itself is usually assumed to be intractable. Both of these assumptions are inaccurate. For example, numbness and tingling in glove and stocking distribution are common accompaniments of longstanding diabetes mellitus, but only about 10% of patients with diabetic neuropathy consider these sensory changes to be painful (1. Anticonvulsant and antidepressant treatments provide effective analgesia in up to 50% of patients with chronic neuropathic pain (2 and there is a growing body of high-quality evidence that controlled-release opioid analgesics provide substantial pain relief in a further subset of patients (3-6. Even with polypharmacy, this still leaves perhaps 20% to 30% of chronic neuropathic pain sufferers lacking adequate analgesia, and side effects can be problematic. In addition, central pain appears to be more refractory to opioid treatment than pain due to peripheral nerve injury (7.

  6. Placebo manipulations reduce hyperalgesia in neuropathic pain.

    Science.gov (United States)

    Petersen, Gitte Laue; Finnerup, Nanna Brix; Nørskov, Kathrine Næsted; Grosen, Kasper; Pilegaard, Hans K; Benedetti, Fabrizio; Price, Donald D; Jensen, Troels Staehelin; Vase, Lene

    2012-06-01

    Several studies have shown that placebo analgesia effects can be obtained in healthy volunteers, as well as patients suffering from acute postoperative pain and chronic pain conditions such as irritable bowel syndrome. However, it is unknown whether placebo analgesia effects can be elicited in chronic pain conditions with a known pathophysiology such as a nerve injury. Nineteen patients who had developed neuropathic pain after thoracotomy were exposed to a placebo manipulation in which they received either open or hidden administrations of lidocaine. Before the treatment, the patients rated their levels of spontaneous pain and expected pain and completed a questionnaire on their emotional feelings (Positive Affect Negative Affect Schedule) and went through quantitative sensory testing of evoked pain (brush and cold allodynia, heat pain tolerance, area of pinprick hyperalgesia, wind-up-like pain after pinprick stimulation). The placebo manipulation significantly reduced the area of pinprick hyperalgesia (P=.027), and this placebo effect was significantly related to low levels of negative affect (P=.008; R(2)=0.362) but not to positive affect or expected pain levels. No placebo effect was observed in relation to spontaneous pain or evoked pain, which is most likely due to low pain levels resulting in floor effects. This is the first study to demonstrate a placebo effect in neuropathic pain. The possible mechanisms underlying the placebo effects in hyperalgesia are discussed, and implications for treatment are outlined.

  7. Tetrahydrocannabinol (Delta 9-THC Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey

    Directory of Open Access Journals (Sweden)

    Janet Weber

    2009-01-01

    Full Text Available Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol (delta 9-THC may be a promising therapeutic agent. We administered in 172 patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. Thus, 124 patients were assessed retrospectively in a multicenter telephone survey. Reported changes in pain intensity, recorded on a numeric rating scale (NRS, Pain Disability Index (PDI, Medical Outcomes Short-Form (SF-12, Quality of Life Impairment by Pain (QLIP, Hospital Anxiety Depression Scale (HADS, and amount of concomitant pain medication were recorded. Psychometric parameters (PDI, SF-12, QLIP, HADS and pain intensity improved significantly during delta 9-THC treatment. Opioid doses were reduced and patients perceived THC therapy as effective with tolerable side effects. About 25% of the patients, however, did not tolerate the treatment. Therapy success and tolerance can be assessed by a transient delta 9-THC titration and its maintained administration for several weeks. The present survey demonstrates its ameliorating potential for the treatment of chronic pain in central neuropathy and fibromyalgia. A supplemental delta 9-THC treatment as part of a broader pain management plan therefore may represent a promising coanalgesic therapeutic option.

  8. The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

    Science.gov (United States)

    Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

    2016-08-01

    Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc.

  9. Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

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    Xu, Ya-Qiong [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Jin, Shao-Ju [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China); Liu, Ning [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Li, Yu-Xiang [College of Nursing, Ningxia Medical University, Yinchuan 750004 (China); Zheng, Jie [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Ma, Lin [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Du, Juan; Zhou, Ru [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Zhao, Cheng-Jun [Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750000 (China); Niu, Yang [Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan 750004 (China); Sun, Tao [Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750004 (China); Yu, Jian-Qiang, E-mail: Yujq910315@163.com [Department of Pharmacology, Ningxia Medical university, Yinchuan 750000 (China); Luohe Medical College, Luohe 462002, Henan Province (China)

    2014-09-05

    Highlights: • Aloperine has anti-nociceptive effects on neuropathic pain induced CCI. • Aloperine reduces ROS in neuropathic pain mice. • Aloperine down-regulates the expression of NF-κB and its downstream pro-inflammatory cytokines in neuropathic pain mice. - Abstract: Objective: To investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. Methods: Mechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. Results: Administration of ALO (80 mg/kg and 40 mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80 mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10 mg/kg (i.p.). Conclusion: ALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

  10. Nurse’s knowledge of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ali Yavuz Karahan

    2014-08-01

    Full Text Available The aim of our study was to determine the levels of information and awareness of the nurses who work on neuropathic pain in the departments of physical medicine and rehabilitation, neurology and neurosurgery. A total of 60 nurses (20 per each department who work in the physical medicine and rehabilitation, neurology and neurosurgery departments of Beyhekim State Hospital of Konya in Turkey took part in the study. The level of information and awareness of the nurses on neuropathic pain were assessed via a questionnaire prepared by specialists in the light of recent literature. The questionnaire was composed of 30 questions including the definition, symptoms, treatment and management of neuropathic pain. None of 60 nurses participating in the study were given any previous in-service training on neuropathic pain. According to the assessments, 80% of nurses (48 were found not to have sufficient knowledge about definition of neuropathic pain; 83.3% (50 about diseases causing neuropathic pain; 83.3% (50 about symptoms of neuropathic pain; and 90% (54 about management of neuropathic pain. The findings obtained from the nurses of these three departments showed no statistically significant relation. Our findings indicated that the knowledge of participants’ about neuropathic pain who work in these three departments seriously lack of information. Informing nurses about neuropathic pain during in-service training will be an important step towards improving the quality of services provided.

  11. PHARMACOTHERAPY IN ELDERLY NEUROPATHIC PAIN

    Directory of Open Access Journals (Sweden)

    Thomas Eko P

    2013-10-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 The incidence of pain increases with age. Neuropathic pain are common in elderly patients and pose challenges in both their diagnosis and treatment. The most common neuropathic pain in elderly are radiculopathy due to foraminal or spinal stenosis, diabetic neuropathy, and postherpetic neuralgia. Pain in the elderly is often unrecognized and undertreated. The main problem with pain in older adults relates to impaired quality of life secondary to pain which may be expressed by depression (including increased suicide risk, anxiety, sleep disruption, appetite disturbance, and weight loss, cognitive impairment, and limitations in the performance of daily activities. Pain management in elderly patients requires a different perspective from that of younger patients. Causes, comorbidities, and responses to both pain and its treatment differ between young healthy and older patients. Effective pain management in elderly patients should include both pharmacologic and nonpharmacologic strategies. Pharmacological approaches are the first line of pain management in older person for neuropathic pain. Pharmacologic strategies call for administration of nonopioid analgesics, opioid analgesics, and adjuvant medication. Polypharmacy, drug-drug and drug-disease interactions, age-associated changes in drug metabolism, and the high frequency of adverse drug reactions need to be carefully considered in using medications in this population /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso

  12. The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.

    Science.gov (United States)

    Eisenberg, Elon; Ogintz, Miri; Almog, Shlomo

    2014-09-01

    Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC₀→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs. PMID:25118789

  13. Intrathecal ziconotide for neuropathic pain: a review.

    Science.gov (United States)

    Rauck, Richard L; Wallace, Mark S; Burton, Allen W; Kapural, Leonardo; North, James M

    2009-01-01

    Neuropathic pain is a considerable burden that affects activities of daily living. The management of neuropathic pain can be challenging because of multiple etiologies and complex manifestations. Ziconotide is a nonopioid intrathecal (IT) analgesic option for patients with neuropathic pain refractory to conventional treatments. The objective of this article is to review the published literature on ziconotide for the treatment of neuropathic pain. Relevant publications were identified through searches of all years of 6 databases, which included PubMed, EMBASE, and CINAHL. Search terms used were ziconotide, SNX-111, MVIIA, Prialt, and neuropathic pain. Publications were included if ziconotide was intrathecally administered (either alone or in combination with other IT agents) to treat neuropathic pain of any etiology and if pain assessment was an outcome measure. Data extracted included study design, IT drug doses, pain outcome measures, and adverse events (AEs). Twenty-eight articles met the inclusion criteria: 5 were preclinical studies and 23 were clinical studies. In the preclinical studies, ziconotide demonstrated antiallodynic effects on neuropathic pain. Data from double-blind, placebo-controlled (DBPC) trials indicated that patients with neuropathic pain reported a mean percent improvement in pain score with ziconotide monotherapy that ranged from 15.7% to 31.6%. A low starting dose and slow titration of ziconotide resulted in an improved safety profile in the aforementioned trials. Common AEs associated with ziconotide include nausea and/or vomiting, dizziness, confusion, urinary retention, and somnolence. Evidence from DBPC trials, open-label studies, case series, and case studies suggests that ziconotide, as either monotherapy or in combination with other IT drugs, is a potential therapeutic option for patients with refractory neuropathic pain. Additional studies are needed to establish the long-term efficacy and safety of ziconotide for neuropathic pain

  14. Electroacupuncture attenuates neuropathic pain after brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Shenyu Zhang; Hailiang Tang; Junming Zhou; Yudong Gu

    2014-01-01

    Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root (associated with upper-limb chronic neuropathic pain) were given electroacu-puncture stimulation at bilateralQuchi(LI11),Hegu(LI04),Zusanli(ST36) andYanglingquan (GB34). After electroacupuncture therapy, chronic neuropathic pain in the rats’ upper limbs was signiifcantly attenuated. Immunolfuorescence staining showed that the expression of β-endorphins in the arcuate nucleus was signiifcantly increased after therapy. Thus, experimental ifndings indi-cate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulatingβ-endorphin expression.

  15. Effectiveness of pregabalin for the treatment of chronic low back pain with accompanying lower limb pain (neuropathic component: a non-interventional study in Japan

    Directory of Open Access Journals (Sweden)

    Taguchi T

    2015-08-01

    Full Text Available Toshihiko Taguchi,1 Ataru Igarashi,2 Stephen Watt,3 Bruce Parsons,3 Alesia Sadosky,3 Kazutaka Nozawa,4 Kazuhiro Hayakawa,4 Tamotsu Yoshiyama,4 Nozomi Ebata,4 Koichi Fujii4 1Department of Orthopaedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan; 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 3Pfizer Inc., New York, NY, USA; 4Pfizer Japan, Inc., Tokyo, Japan Objective: To evaluate the impact of pregabalin on sleep, pain, function, and health status in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP under routine clinical practice. Methods: This prospective, non-interventional, observational study enrolled Japanese adults (≥18 years with CLBP-NeP of duration ≥3 months and severity ≥5 on a numerical rating scale (0= no pain, 10= worst possible pain. Treatment was 8 weeks with pregabalin (n=157 or usual care alone (n=174; choice of treatment was determined by the physician. The primary efficacy outcome was change from baseline to 8 weeks in pain-related interference with sleep, assessed using the Pain-Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep. Secondary endpoints were changes in PRSIS at week 4, and changes at weeks 4 and 8 in pain (numerical rating scale, function (Roland-Morris Disability Questionnaire, and quality of life (EuroQol 5D-5L; global assessments of change were evaluated from the clinician and patient perspectives at the final visit. Results: Demographic characteristics were similar between cohorts, but clinical characteristics suggested greater disease severity in the pregabalin group including a higher mean (standard deviation pain score, 6.3 (1.2 versus 5.8 (1.1 (P<0.001. For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week 8, least-squares mean changes of -1.3 versus

  16. Pharmacological management of neuropathic pain following spinal cord injury.

    Science.gov (United States)

    Baastrup, Cathrine; Finnerup, Nanna B

    2008-01-01

    Spinal cord injury (SCI) has a number of severe and disabling consequences, including chronic pain, and around 40% of patients develop persistent neuropathic pain. Pain following SCI has a detrimental impact on the patient's quality of life and is a major specific healthcare problem in its own right. Thus far, there is no cure for the pain and oral pharmaceutical intervention is often inadequate, commonly resulting in a reduction of only 20-30% in pain intensity. Neuropathic pain sensations are characterized by spontaneous persistent pain and a range of abnormally evoked responses, e.g. allodynia (pain evoked by normally non-noxious stimuli) and hyperalgesia (an increased response to noxious stimuli). Neuropathic pain following SCI may be present at or below the level of injury. Oral pharmacological agents used in the treatment of neuropathic pain act either by depressing neuronal activity, by blocking sodium channels or inhibiting calcium channels, by increasing inhibition via GABA agonists, by serotonergic and noradrenergic reuptake inhibition, or by decreasing activation via glutamate receptor inhibition, especially by blocking the NMDA receptor. At present, only ten randomized, double-blind, controlled trials have been performed on oral drug treatment of pain after SCI, the results of most of which were negative. The studies included antidepressants (amitriptyline and trazodone), antiepileptics (gabapentin, pregabalin, lamotrigine and valproate) and mexiletine. Gabapentin, pregabalin and amitriptyline showed a significant reduction in neuropathic pain following SCI. Cannabinoids have been found to relieve other types of central pain, and serotonin noradrenaline reuptake inhibitors as well as opioids relieve peripheral neuropathic pain and may be used to treat patients with SCI pain. PMID:18484790

  17. Estimating the burden of disease in chronic pain with and without neuropathic characteristics: does the choice between the EQ-5D and SF-6D matter?

    Science.gov (United States)

    Torrance, Nicola; Lawson, Kenny D; Afolabi, Ebenezer; Bennett, Michael I; Serpell, Michael G; Dunn, Kate M; Smith, Blair H

    2014-10-01

    The EQ-5D and Short Form (SF)12 are widely used generic health-related quality of life (HRQoL) questionnaires. They can be used to derive health utility index scores, on a scale where 0 is equivalent to death and 1 represents full health, with scores less than zero representing states "worse than death." We compared EQ-5D or SF-6D health utility index scores in patients with no chronic pain, and chronic pain with and without neuropathic characteristics (NC), and to explore their discriminant ability for pain severity. Self-reported health and chronic pain status was collected as part of a UK general population survey (n=4451). We found moderate agreement between individual dimensions of EQ-5D and SF-6D, with most highly correlated dimensions found for mental health and anxiety/depression, role limitations and usual activities, and pain and pain/discomfort. Overall 43% reported full health on the EQ-5D, compared with only 4.2% on the SF-6D. There were significant differences in mean utilities for chronic pain with NC (EQ-5D 0.47 vs SF-6D 0.62) and especially for severe pain (EQ-5D 0.33 vs SF-6D 0.58). On the EQ-5D, 17% of those with chronic pain with NC and 3% without NC scored "worse than death," a state which is not possible using the SF-6D. Health utilities derived from EQ-5D and SF-12/36 can discriminate between group differences for chronic pain with and without NC and greater pain severity. However, the instruments generate widely differing HRQoL scores for the same patient groups. The choice between using the EQ-5D or SF-6D matters greatly when estimating the burden of disease.

  18. Molecular mechanisms underlying the effects of acupuncture on neuropathic pain**

    Institute of Scientific and Technical Information of China (English)

    Ziyong Ju; Huashun Cui; Xiaohui Guo; Huayuan Yang; Jinsen He; Ke Wang

    2013-01-01

    Acupuncture has been used to treat neuropathic pain for a long time, but its mechanisms of action remain unknown. In this study, we observed the effects of electroacupuncture and manual acu-puncture on neuropathic pain and on ephrin-B/EphB signaling in rats models of chronic constriction injury-induced neuropathic pain. The results showed that manual acupuncture and elec-puncture significantly reduced mechanical hypersensitivity fol owing chronic constriction injury, es-pecial y electroacupuncture treatment. Real-time PCR results revealed that ephrin-B1/B3 and EphB1/B2 mRNA expression levels were significantly increased in the spinal dorsal horns of chronic constriction injury rats. Electroacupuncture and manual acupuncture suppressed the high sion of ephrin-B1 mRNA, and elevated EphB3/B4 mRNA expression. Electroacupuncture signifi-cantly enhanced the mRNA expression of ephrin-B3 and EphB3/B6 in the dorsal horns of neuro-pathic pain rats. Western blot results revealed that electroacupuncture in particular, and manual acupuncture, significantly up-regulated ephrin-B3 protein levels in rat spinal dorsal horns. The re-sults of this study suggest that acupuncture could activate ephrin-B/EphB signaling in neuropathic pain rats and improve neurological function.

  19. Effects of 660- and 980-nm low-level laser therapy on neuropathic pain relief following chronic constriction injury in rat sciatic nerve.

    Science.gov (United States)

    Masoumipoor, M; Jameie, S B; Janzadeh, A; Nasirinezhad, F; Soleimani, M; Kerdary, M

    2014-09-01

    Neuropathic pain (NP) is one of the most suffered conditions in medical disciplines. The role of reactive oxygen species (ROS) and oxidative stress in the induction of NP was studied by many researchers. Neuropathies lead to medical, social, and economic isolation of the patient, so various therapies were used to treat or reduce it. During the recent years, low-level laser therapy (LLLT) has been used in certain areas of medicine and rehabilitation. Chronic constriction injury (CCI) is a well-known model for neuropathic pain studies. In order to find the effects of different wavelengths of LLLT on the injured sciatic nerve, the present research was done. Thirty Wistar adult male rats (230-320 g) were used in this study. The animals were randomly divided into three groups (n = 10). To induce neuropathic pain for the sciatic nerve, the CCI technique was used. Low-level laser of 660 and 980 nm was used for two consecutive weeks. Thermal and mechanical hyperalgesia was done before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. CCI decreased the pain threshold, whereas both wavelengths of LLLT for 2 weeks increased mechanical and thermal threshold significantly. A comparison of the mechanical and thermal threshold showed a significant difference between the therapeutic effects of the two groups that received LLLT. Based on our findings, the laser with a 660-nm wavelength had better therapeutic effects than the laser with a 980-nm wavelength, so the former one may be used for clinical application in neuropathic cases; however, it needs more future studies.

  20. Duloxetine and 8-OH-DPAT, but not fluoxetine, reduce depression-like behaviour in an animal model of chronic neuropathic pain.

    Science.gov (United States)

    Hu, Bing; Doods, Henri; Treede, Rolf-Detlef; Ceci, Angelo

    2016-04-21

    The current study assessed whether antidepressant and/or antinociceptive drugs, duloxetine, fluoxetine as well as (±)-8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), are able to reverse depression-like behaviour in animals with chronic neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve in rats was selected as neuropathic pain model. Mechanical hypersensitivity and depression-like behaviour were evaluated 4 weeks after surgery by "electronic algometer" and forced swimming test (FST), which measured the time of immobility, and active behaviours climbing and swimming. The selective noradrenergic and serotonergic uptake blocker duloxetine (20mg/kg) and the selective 5-HT1A agonist 8-OH-DPAT (0.5mg/kg) significantly reversed both mechanical hypersensitivity and depression-like behaviour in CCI animals. Duloxetine significantly reversed depression-like behaviour in CCI rats by increasing the time of climbing and swimming, while 8-OH-DPAT attenuated depression-like behaviour mainly by increasing the time of swimming. However, the selective serotonergic uptake blocker fluoxetine (20mg/kg) failed to attenuate mechanical hypersensitivity and depression-like behaviour, possibly due to confounding pro-nociceptive actions at 5-HT3 receptors. These data suggest to target noradrenergic and 5-HT1A receptors for treatment of chronic pain and its comorbidity depression. PMID:26987721

  1. Cost-effectiveness analysis of pregabalin for treatment of chronic low back pain in patients with accompanying lower limb pain (neuropathic component) in Japan

    Science.gov (United States)

    Igarashi, Ataru; Akazawa, Manabu; Murata, Tatsunori; Taguchi, Toshihiko; Sadosky, Alesia; Ebata, Nozomi; Willke, Richard; Fujii, Koichi; Doherty, Jim; Kobayashi, Makoto

    2015-01-01

    Objective To assess the cost-effectiveness of pregabalin for the treatment of chronic low back pain with accompanying neuropathic pain (CLBP-NeP) from the health care payer and societal perspectives. Methods The cost-effectiveness of pregabalin versus usual care for treatment of CLBP-NeP was evaluated over a 12-month time horizon using the incremental cost-effectiveness ratio (ICER). Quality-adjusted life years (QALYs), derived from the five-dimension, five-level EuroQol (EQ-5D-5L) questionnaire, was the measure of effectiveness. Medical costs and productivity losses were both calculated. Expected costs and outcomes were estimated via cohort simulation using a state-transition model, which mimics pain state transitions among mild, moderate, and severe pain. Distributions of pain severity were obtained from an 8-week noninterventional study. Health care resource consumption for estimation of direct medical costs for pain severity levels was derived from a physician survey. The ICER per additional QALY gained was calculated and sensitivity analyses were performed to evaluate the robustness of the assumptions across a range of values. Results Direct medical costs and hospitalization costs were both lower in the pregabalin arm compared with usual care. The estimated ICERs in the base case scenarios were approximately ¥2,025,000 and ¥1,435,000 per QALY gained with pregabalin from the payer and societal perspectives, respectively; the latter included indirect costs related to lost productivity. Sensitivity analyses using alternate values for postsurgical pain scores (0 and 5), initial pain severity levels (either all moderate or all severe), and the actual EQ-5D-5L scores from the noninterventional study showed robustness of results, with ICERs that were similar to the base case. Development of a cost-effectiveness acceptability curve showed high probability (≥75%) of pregabalin being cost-effective. Conclusion Using data and assumptions from routine clinical

  2. Novel Epigallocatechin-3-Gallate (EGCG) Derivative as a New Therapeutic Strategy for Reducing Neuropathic Pain after Chronic Constriction Nerve Injury in Mice

    Science.gov (United States)

    Xifró, Xavier; Vidal-Sancho, Laura; Boadas-Vaello, Pere; Turrado, Carlos; Alberch, Jordi; Puig, Teresa; Verdú, Enrique

    2015-01-01

    Neuropathic pain is common in peripheral nerve injury and often fails to respond to ordinary medication. Here, we investigated whether the two novel epigallocatechin-3-gallate (EGCG) polyphenolic derivatives, compound 23 and 30, reduce the neuropathic pain in mice chronic constriction nerve injury (CCI). First, we performed a dose-response study to evaluate nociceptive sensation after administration of EGCG and its derivatives 23 and 30, using the Hargreaves test at 7 and 21 days after injury (dpi). We daily administered EGCG, 23 and 30 (10 to 100 mg/Kg; i.p.) during the first week post-CCI. None of the doses of compound 23 caused significant pain diminution, whereas 50mg/kg was optimal for both EGCG and 30 to delay the latency of paw withdrawal. With 50 mg/Kg, we showed that EGCC prevented the thermal hyperalgesia from 7 to 21 dpi and compound 30 from 14 to 56 dpi. To evaluate the molecular mechanisms underpinning why EGCG and compound 30 differentially prevented the thermal hyperalgesia, we studied several biochemical parameters in the dorsal horn of the spinal cord at 14 and 56 dpi. We showed that the effect observed with EGCG and compound 30 was related to the inhibition of fatty acid synthase (FASN), a known target of these polyphenolic compounds. Additionally, we observed that EGCG and compound 30 reduced the expression of CCI-mediated inflammatory proteins and the nuclear localization of nuclear factor-kappa B at 14 dpi, but not at 56 dpi. We also strongly detected a decrease of synaptic plasma membrane levels of N-methyl-D-asparte receptor 2B in CCI-mice treated with compound 30 at 56 dpi. Altogether, compound 30 reduced the chronic thermal hyperalgesia induced by CCI better than the natural compound EGCG. Thus, our findings provide a rationale for the preclinical development of compound 30 as an agent to treat neuropathic pain. PMID:25855977

  3. Antioxidant Activity of Sestrin 2 Controls Neuropathic Pain After Peripheral Nerve Injury

    OpenAIRE

    Kallenborn-Gerhardt, Wiebke; Lu, Ruirui; Syhr, Katharina M.J.; Heidler, Juliana; von Melchner, Harald; Geisslinger, Gerd; Bangsow, Thorsten; Schmidtko, Achim

    2013-01-01

    Aims: Neuropathic pain is a chronic debilitating disease that is often unresponsive to currently available treatments. Emerging lines of evidence indicate that reactive oxygen species (ROS) are required for the development and maintenance of neuropathic pain. However, little is known about endogenous mechanisms that neutralize the pain-relevant effects of ROS. In the present study, we tested whether the stress-responsive antioxidant protein Sestrin 2 (Sesn2) blocks the ROS-induced neuropathic...

  4. A role for uninjured afferents in neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Richard A. Meyer; Matthias Ringkamp

    2008-01-01

    Diseases and injuries to the nervous system can lead to a devastating chronic pain condition called neuropathic pain. We review changes that occur in the peripheral nervous system that may play a role in this disease. Common animal models for neuropathic pain involve an injury to one or more peripheral nerves. Following such an injury, the nerve fibers that have been injured exhibit many abnormal properties including the development of spontaneous neural activity as well as a change in the expression of certain genes in their cell body. Recent data indicate that adjacent, uninjured nerve fibers also exhibit significant changes. These changes are thought to be driven by injury-induced alterations in the milieu surrounding the uninjured nerve and nerve terminals. Thus, alteration in neural signaling in both injured and uninjured neurons play a role in the development of neuropathic pain after peripheral nerve injury.

  5. A double-blinded randomised controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component.

    Science.gov (United States)

    Yousef, A A; Al-deeb, A E

    2013-03-01

    Persistent mechanical irritation of the nerve root sets up a series of events mediating sensitisation of the dorsal roots and dorsal horns in the spinal cord. Current evidence supports the role of magnesium in blocking central sensitisation through its effect on N-methyl-d-aspartate receptors. We studied the role of sequential intravenous and oral magnesium infusion in patients with chronic low back pain with a neuropathic component. We recruited a cohort of 80 patients with chronic low back pain with a Leeds Assessment of Neuropathic Signs and Symptoms pain scale score ≥ 12, who were receiving a physical therapy programme. All patients were treated with anticonvulsants, antidepressants and simple analgesics; in addition 40 patients received placebo for 6 weeks (control group), while the other 40 patients received an intravenous magnesium infusion for 2 weeks followed by oral magnesium capsules for another 4 weeks (magnesium group). Patients were asked to rate their pain using a numerical rating scale. Lumbar spine range of motion was also determined using a long-arm goniometer. In the magnesium group, the patients' numerical rating scales revealed a significant reduction in pain intensity. The mean (SD) pre-treatment value was 7.5 (2.2) compared with 4.7 (1.8) at 6 months (p = 0.034). The reduction in pain intensity was accompanied by significant improvement in lumbar spine range of motion during the follow-up period. The mean (SD) values of flexion, extension and lateral flexion movements before treatment and at 6-month follow up were 22.2 (8.4) vs 34.7 (11.5) (p = 0.018), 11.8 (3.4) vs 16.9 (3.5) (p = 0.039), 11.4 (3.6) vs 17.2 (4.4) (p = 0.035), respectively. Our findings show that a 2-week intravenous magnesium infusion followed by 4 weeks of oral magnesium supplementation can reduce pain intensity and improve lumbar spine mobility during a 6-month period in patients with refractory chronic low back pain with a neuropathic component.

  6. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2014-01-01

    Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  7. Nurse’s Knowledge of Neuropathic Pain

    OpenAIRE

    Ali Yavuz Karahan; Seher Kucuksarac; Neslihan Soran; Banu Ordahan; Levent Tekin; Aynur Basaran

    2014-01-01

    The aim of our study was to determine the levels of information and awareness of the nurses who work on neuropathic pain in the departments of physical medicine and rehabilitation, neurology and neurosurgery. A total of 60 nurses (20 per each department) who work in the physical medicine and rehabilitation, neurology and neurosurgery departments of Beyhekim State Hospital of Konya in Turkey took part in the study. The level of information and awareness of the nurses on neuropathic pain were a...

  8. Molecular hydrogen attenuates neuropathic pain in mice.

    Science.gov (United States)

    Kawaguchi, Masanori; Satoh, Yasushi; Otsubo, Yukiko; Kazama, Tomiei

    2014-01-01

    Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting. PMID:24941001

  9. Molecular hydrogen attenuates neuropathic pain in mice.

    Directory of Open Access Journals (Sweden)

    Masanori Kawaguchi

    Full Text Available Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2 as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation. When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation, hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting.

  10. Effects of Saffron (Crocus sativus L.) Stigma Extract and its Active Constituent Crocin on Neuropathic Pain Responses in a Rat Model of Chronic Constriction Injury.

    Science.gov (United States)

    Safakhah, Hossein Ali; Taghavi, Tahereh; Rashidy-Pour, Ali; Vafaei, Abbas Ali; Sokhanvar, Mina; Mohebbi, Narges; Rezaei-Tavirani, Mostafa

    2016-01-01

    This study was designed to investigate the therapeutic effects of saffron (Crocus sativus L.) and its main constituent crocin on neuropathic pain behavioral responses induced by chronic constriction injury (CCI) in rats. Adult male Wistar rats (200 to 250 g) were randomly assigned into 5 groups: Sham + saline, CCI + saline, CCI+ saffron (30 mg/kg), CCI + crocin (15 mg/kg) and CCI + crocin (30 mg/kg). CCI was induced by applying 4 loose ligatures around the sciatic nerve. Two weeks after nerve lesion, injections of saline, saffron or crocin were started and continued until 26(th) day post-surgery. Pain behavioral responses including mechanical allodynia (von Frey filament testing) and thermal hyperalgesia were measured in 14, 17, 20, 23, 26, and 40(th) days after CCI. CCI significantly increased pain behavioral responses. Saffron and crocin (30 mg/kg) decreased thermal hyperalgesia and mechanical allodynia on day 26, and this effect continued until the day 40. Crocin at lower dose (15 mg/kg) was ineffective. These findings indicate that treatment of saffron and crocin after CCI may have a therapeutic effect against neuropathic pain, suggesting that these substances may offer new strategies for the treatment of this highly debilitating condition.

  11. A case of chronic neuropathic pain treated with auricula injection of local anaesthetic

    Directory of Open Access Journals (Sweden)

    Paolo Barbagli

    2006-09-01

    Full Text Available The case under discussion is that of a 69 years old woman, who has suffered from saphenus nerve neuralgia for about one and a half years. This illness has proved resistant to all the therapeutic treatments she has undergone. The case has been solved in just one session of a rarely used technique, not even well-documented in literature: the injection of local anaesthetic into some auricular points. After about one month of significant aggravation, the pain has disappeared and it has never reappeared throughout the 1-year follow up. The new denomination suggested for this technique is neural-auriculotherapy, which well summarizes the therapeutic branches from which it stems.

  12. A comparison of coping strategies in patients with fibromyalgia, chronic neuropathic pain, and pain-free controls

    DEFF Research Database (Denmark)

    Baastrup, Sidsel; Schultz, Rikke; Moore, Rod;

    2016-01-01

    did not cope differently with pain. The only difference between the groups was that FM patients felt more in control of their pain than NP patients. Both patient groups used more maladaptive/passive coping strategies, but surprisingly also more adaptive/active coping strategies than healthy controls...

  13. Effect of TRPV4-p38 MAPK Pathway on Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

    Directory of Open Access Journals (Sweden)

    Yu-Juan Qu

    2016-01-01

    Full Text Available The aim of this study was to investigate the relationships among TRPV4, p38, and neuropathic pain in a rat model of chronic compression of the dorsal root ganglion. Mechanical allodynia appeared after CCD surgery, enhanced via the intrathecal injection of 4α-phorbol 12,13-didecanoate (4α-PDD, an agonist of TRPV4 and anisomycin (an agonist of p38, but was suppressed by Ruthenium Red (RR, an inhibitor of TRPV4 and SB203580 (an inhibitor of p38. The protein expressions of p38 and P-p38 were upregulated by 4α-PDD and anisomycin injection but reduced by RR and SB203580. Moreover, TRPV4 was upregulated by 4α-PDD and SB203580 and downregulated by RR and anisomycin. In DRG tissues, the numbers of TRPV4- or p38-positive small neurons were significantly changed in CCD rats, increased by the agonists, and decreased by the inhibitors. The amplitudes of ectopic discharges were increased by 4α-PDD and anisomycin but decreased by RR and SB203580. Collectively, these results support the link between TRPV4 and p38 and their intermediary role for neuropathic pain in rats with chronic compression of the dorsal root ganglion.

  14. Ameliorative potential of Butea monosperma on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Venkata R.K. Thiagarajan

    2012-12-01

    Full Text Available The present study was designed to investigate the ameliorative role of ethanolic extract from leaves of Butea monosperma in chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia & allodynia in the left hind paw and tail thermal hyperalgesia. Further on, thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of Butea monosperma leaves and pregabalin (serving as positive control were administered for 14 consecutive days starting from the day of surgery. CCI resulted in significant changes in behavioural and biochemical parameters. Pretreatment of Butea monosperma attenuated CCI induced development of behavioural, biochemical and histopathological alterations in a dose dependent manner, which is comparable to that of pregabalin pretreated group. These findings may be attributed to its potential anti-oxidative, neuroprotective and calcium channel modulatory actions of Butea monosperma.O presente trabalho visou investigar o papel do extrato etanólico de folhas de Butea monosperma no alívio da dor neuropática pela injúria de constrição crônica (CCI do nervo ciático induzida em ratos. Placa quente, gota de acetona, pressão na pata, testes de imersão de pelo e cauda de Von Frey foram utilizados para acessar o grau de hiperalgesia térmica, alodinia química fria, hiperalgesia mecânica e alodinia na pata trazeira esquerda e hiperalgesia térmica da cauda. Além disso, substâncias reativas com ácido tiobarbitúrico (TBARS, glutatião reduzido (GSH e níveis de cálcio total foram estimados para acessar as altera

  15. Classification of neuropathic pain in cancer patients

    DEFF Research Database (Denmark)

    Brunelli, Cinzia; Bennett, Michael I; Kaasa, Stein;

    2014-01-01

    Neuropathic pain (NP) in cancer patients lacks standards for diagnosis. This study is aimed at reaching consensus on the application of the International Association for the Study of Pain (IASP) special interest group for neuropathic pain (NeuPSIG) criteria to the diagnosis of NP in cancer patients...... was found on the statement "the pathophysiology of NP due to cancer can be different from non-cancer NP" (MED=9, IQR=2). Satisfactory consensus was reached for the first 3 NeuPSIG criteria (pain distribution, history, and sensory findings; MEDs⩾8, IQRs⩽3), but not for the fourth one (diagnostic test....../imaging; MED=6, IQR=3). Agreement was also reached on clinical examination by soft brush or pin stimulation (MEDs⩾7 and IQRs⩽3) and on the use of PRO descriptors for NP screening (MED=8, IQR=3). Based on the study results, a clinical algorithm for NP diagnostic criteria in cancer patients with pain...

  16. Discovery of Fused Triazolo-thiadiazoles as Inhibitors of TNF-alpha: Pharmacophore Hybridization for Treatment of Neuropathic Pain

    OpenAIRE

    Sharma, Monika; Deekshith, Vanamala; Semwal, Arvind; Sriram, Dharmarajan; Yogeeswari, Perumal

    2012-01-01

    Introduction Neuropathic pain is a complex, chronic pain state that is usually accompanied by tissue injury. With neuropathic pain, the nerve fibers themselves may be damaged, dysfunctional, or injured. Methods A series of pharmacophoric hybrids of substituted aryl semicarbazides incorporated into a fused triazolo-thiadiazole nucleus were synthesized and evaluated for neuropathic pain activity. After the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluat...

  17. Botulinum Toxin Treatment of Neuropathic Pain.

    Science.gov (United States)

    Mittal, Shivam Om; Safarpour, Delaram; Jabbari, Bahman

    2016-02-01

    Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most-effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain. PMID:26866499

  18. Hemiplegic shoulder pain: evidence of a neuropathic origin.

    Science.gov (United States)

    Zeilig, Gabi; Rivel, Michal; Weingarden, Harold; Gaidoukov, Evgeni; Defrin, Ruth

    2013-02-01

    Hemiplegic shoulder pain (HSP) is common after stroke. Whereas most studies have concentrated on the possible musculoskeletal factors underlying HSP, neuropathic aspects have hardly been studied. Our aim was to explore the possible neuropathic components in HSP, and if identified, whether they are specific to the shoulder or characteristic of the entire affected side. Participants included 30 poststroke patients, 16 with and 14 without HSP, and 15 healthy controls. The thresholds of warmth, cold, heat-pain, touch, and graphesthesia were measured in the intact and affected shoulder and in the affected lower leg. They were also assessed for the presence of allodynia and hyperpathia, and computed tomography/magnetic resonance imaging scans of the brain were reviewed. In addition, chronic pain was characterized. Participants with HSP exhibited higher rates of parietal lobe damage (P<0.05) compared to those without HSP. Both poststroke groups exhibited higher sensory thresholds than healthy controls. Those with HSP had higher heat-pain thresholds in both the affected shoulder (P<0.001) and leg (P<0.01), exhibited higher rates of hyperpathia in both these regions (each P<0.001), and more often reported chronic pain throughout the affected side (P<0.001) than those without HSP. The more prominent sensory alterations in the shoulder region suggest that neuropathic factors play a role in HSP. The clinical evidence of damage to the spinothalamic-thalamocortical system in the affected shoulder and leg, the presence of chronic pain throughout the affected side, and the more frequent involvement of the parietal cortex all suggest that the neuropathic component is of central origin.

  19. The players involved in neuropathic pain pathophysiology

    Directory of Open Access Journals (Sweden)

    Francesco Amato

    2015-03-01

    Full Text Available The author presents a well documentated review on the receptorial mechanisms involved in the neuropathic pain physiopathology. In particular, the review focus on the role of TRPV1 receptors, on the processes subserving their sensitization and on the role of P2x4R microglial receptors.

  20. [Neuropathic pain: pathophysiology, assessment, and therapy].

    Science.gov (United States)

    Sommer, C

    2013-12-01

    Neuropathic pain is caused by lesions in the somatosensory system. Characteristic but not exclusive features are spontaneous burning pain, electrifying and shooting pain, hyperalgesia, and allodynia. The basic concept of the pathophysiology of neuropathic pain is the combination of peripheral and central sensitization. Knowledge on the molecular mechanisms has grown exponentially in recent years. The problem lies in identifying the individual mechanisms and in determining a comprehensive concept. Progress has also been made in assessment, e.g., methods for detecting dysfunction of nociceptors have significantly improved. In addition, there are many more therapeutic options available than 15 years ago. The drugs available include antidepressants, anticonvulsants, opioids, and topical medications. Data from controlled trials and recommendations from guidelines are available. PMID:24217854

  1. Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside.

    Science.gov (United States)

    Rahn, Elizabeth J; Hohmann, Andrea G

    2009-10-01

    Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need. Here, we review studies evaluating cannabinoids for neuropathic pain management in the clinical and preclinical literature. Neuropathic pain associated with nerve injury, diabetes, chemotherapeutic treatment, human immunodeficiency virus, multiple sclerosis, and herpes zoster infection is considered. In animals, cannabinoids attenuate neuropathic nociception produced by traumatic nerve injury, disease, and toxic insults. Effects of mixed cannabinoid CB(1)/CB(2) agonists, CB(2) selective agonists, and modulators of the endocannabinoid system (i.e., inhibitors of transport or degradation) are compared. Effects of genetic disruption of cannabinoid receptors or enzymes controlling endocannabinoid degradation on neuropathic nociception are described. Specific forms of allodynia and hyperalgesia modulated by cannabinoids are also considered. In humans, effects of smoked marijuana, synthetic Delta(9)-THC analogs (e.g., Marinol, Cesamet) and medicinal cannabis preparations containing both Delta(9)-THC and cannabidiol (e.g., Sativex, Cannador) in neuropathic pain states are reviewed. Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment. Subjective (i.e., rating scales) and objective (i.e., stimulus-evoked) measures of pain and quality of life are considered. Finally, limitations of cannabinoid pharmacotherapies are discussed together with directions for future research. PMID:19789075

  2. Water-soluble lipopolymer delivery of N-methyl-D-aspartic acid receptor 2B siRNA relieves chronic neuropathic pain in rats

    Institute of Scientific and Technical Information of China (English)

    Jianhua Lu; Yuanxiang Tao; Xue Yang; Weifeng Tu; Hao Chen; Jiaxiang Xiong; Chungui Hu

    2011-01-01

    Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B (NR2B) overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA (siRNA) can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer (WSLP) comprised of low molecular weight polyethyleneimine (PEI) and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats (P < 0.01). Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.

  3. Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats

    Directory of Open Access Journals (Sweden)

    Wenzhan Tu

    2015-01-01

    Full Text Available Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

  4. Redox Imbalance in the Peripheral Mechanism Underlying the Mirror-Image Neuropathic Pain Due to Chronic Compression of Dorsal Root Ganglion.

    Science.gov (United States)

    Lv, H; Chen, H; Xu, J J; Jiang, Y S; Shen, Y J; Zhou, S Z; Xu, H; Xiong, Y C

    2016-05-01

    Reactive oxygen species (ROS) play a critical role in the pathogenesis of neuropathic pain, but few studies have examined the role of oxidative stress in the mirror-image neuropathic pain (MINP). The present study was to investigate the role of ROS in MINP caused by chronic compression of the dorsal root ganglion (DRG) (CCD) in a rat model. SD rats were randomly divided into sham group and CCD group. CCD was conducted to induce MINP. CCD rats were intraperitoneally injected with α-Phenyl-N-tert-butyl-nitrone (PBN) at 7 days after surgery. Paw withdrawal mechanical threshold (PWMT) was measured at -1, 1, 3, 5 and 7 days after surgery in sham group and CCD group, and at 8 time points after PBN injection. Rats were sacrificed at 3 and 7 days after surgery in sham group and CCD group and at 0.5 and 2 h after PBN injection, and the superoxide dismutase (SOD) and catalase activities, as well as hydrogen peroxide (H2O2) and malonaldehyde (MDA) contents were determined in the contralateral DRGs. Results showed bilateral PWMT reduced significantly in sham group and CCD group, but it returned to nearly normal level in sham group. MDA content, H2O2 content and SOD activity increased significantly, while catalase activity remained unchanged in CCD rats. PBN at 100 mg/kg significantly attenuated bilateral mechanical hyperalgesia accompanied by the improvement of oxidative stress in the contralateral DRGs. Our results demonstrate that ROS produced in the contralateral DRG are involved in the pathogenesis of CCD induced MINP, and ROS scavenger may be a promising drug for the therapy of MINP. PMID:26471165

  5. [Neurosurgical treatment of chronic pain].

    Science.gov (United States)

    Fontaine, D; Blond, S; Mertens, P; Lanteri-Minet, M

    2015-02-01

    Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy…). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation…) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide…), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications. PMID:25681114

  6. Pain-related psychological distress, self-rated health and significance of neuropathic pain in Danish soldiers injured in Afghanistan

    DEFF Research Database (Denmark)

    Duffy, J R; Warburg, Finn; Koelle, S-F T;

    2015-01-01

    BACKGROUND: Pain and mental health concerns are prevalent among veterans. While the majority of research has focused on chronic pain as an entity, there has been little work directed towards investigating the role of neuropathic pain in relation to psychological comorbidity. As such, we...... hypothesised that participants with signs of neuropathic pain would report higher levels of psychological distress and diminished self-rated health compared to those without a neuropathic component. METHODS: A retrospective review of standardised questionnaires (PainDETECT Questionnaire, Post-traumatic Stress.......008). In multivariate regression analyses, the associations remained when adjusting for socio-demographics and clinical characteristics. CONCLUSIONS: The results from the present study suggest that neuropathic pain is related to increased psychological distress and deterioration in self-rated health in injured soldiers....

  7. Neuropathic pain: A personal case reflection on a critical incident

    Directory of Open Access Journals (Sweden)

    Balaji P Duraisamy

    2011-01-01

    Full Text Available Neuropathic pain is a distressing symptom for the patient and a difficult symptom for the physician to treat. There is lack of evidence-based clinical guidelines for the management of malignant neuropathic pain. The case reflection is a personal account of what has been learnt from a critical incident in a particular patient in the management of neuropathic pain. Psychological issues are known to increase pain percetion and affect the quality of life. The case reflection explores problem areas, defines lacunae in knowledge, and demonstrates active learning of the management of neuropathic pain through reflective practice.

  8. Early dexamethasone relieves trigeminal neuropathic pain.

    Science.gov (United States)

    Han, S R; Yeo, S P; Lee, M K; Bae, Y C; Ahn, D K

    2010-09-01

    The analgesic effects of dexamethasone on neuropathic pain have been controversial. The present study investigated the effects of dexamethasone on mechanical allodynia in rats with mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to injure the inferior alveolar nerve. Nociceptive behavior was examined on each designated day after surgery. Mal-positioned dental implants significantly decreased air-puff thresholds both ipsilateral and contralateral to the injury site. Distinct mechanical hyperalgesia and cold and thermal hypersensitivity were also observed bilaterally. Daily administration of dexamethasone produced prolonged anti-allodynic effects (25 or 50 mg/kg, i.p.), but failed to reduce mechanical allodynia when it had already been established. Therefore, our findings provide that early treatment with dexamethasone is important in the treatment of nociceptive behavior suggestive of trigeminal neuropathic pain. PMID:20581355

  9. Neuropathic pain due to malignancy: Mechanisms, clinical manifestations and therapy

    Directory of Open Access Journals (Sweden)

    Pjević Miroslava

    2004-01-01

    Full Text Available Introduction Neuropathic pain in cancer patients requires a focused clinical evaluation based on knowledge of common neuropathic pain syndromes. Definition Neuropathic pain is a non-nociceptive pain or "differentiation" pain, which suggests abnormal production of impulses by neural tissue that is separated from afferent input. Impulses arise from the peripheral nervous system or central nervous system. Causes of neuropathic pain due to malignancy Neuropathic pain is caused directly by cancer-related pathology (compression/infiltration of nerve tissue, combination of compression/infiltration or by diagnostic and therapeutic procedures (surgical procedures, chemotherapy, radiotherapy. Mechanisms Pathophysiological mechanisms are very complex and still not clear enough. Neuropathic pain is generated by electrical hyperactivity of neurons along the pain pathways. Peripheral mechanisms (primary sensitization of nerve endings, ectopically generated action potentials within damaged nerves, abnormal electrogenesis within sensory ganglia and central mechanisms (loss of input from peripheral nociceptors into dorsal horn, aberrant sprouting within dorsal horn, central sensitization, loss of inhibitory interneurons, mechanisms at higher centers are involved. Diagnosis The quality of pain presents as spontaneous pain (continuous and paroxysmal, abnormal pain (allodynia, hyperalgesia, hyperpathia, paroxysmal pain. Clinical manifestations Clinically, neuropathic pain is described as the pain in the peripheral nerve (cranial nerves, other mononeuropathies, radiculopathy, plexopathy, paraneoplastic peripheral neuropathy and relatively infrequent, central pain syndrome. Therapy Treatment of neuropathic pain remains a challenge for clinicians, because there is no accepted algorithm for analgesic treatment of neuropathic pain. Pharmacotherapy is considered to be the first line therapy. Opioids combined with non-steroidal antiinflammatory drugs are warrented. If

  10. EFNS guidelines on neurostimulation therapy for neuropathic pain

    DEFF Research Database (Denmark)

    EFNS Panel on Neuropathic Pain, Vienna; Cruccu, Giorgio; Aziz, T. Z.;

    2007-01-01

    and to produce relevant recommendations. We searched the literature from 1968 to 2006, looking for neurostimulation in neuropathic pain conditions, and classified the trials according to the EFNS scheme of evidence for therapeutic interventions. Spinal cord stimulation (SCS) is efficacious in failed back surgery...... is inadequate. TENS and r-TMS are non-invasive and suitable as preliminary or add-on therapies. Further controlled trials are warranted for SCS in conditions other than failed back surgery syndrome and CRPS and for MCS and DBS in general. These chronically implanted techniques provide satisfactory pain relief...

  11. Impact of locomotion training with a neurologic controlled hybrid assistive limb (HAL) exoskeleton on neuropathic pain and health related quality of life (HRQoL) in chronic SCI: a case study (.).

    Science.gov (United States)

    Cruciger, Oliver; Schildhauer, Thomas A; Meindl, Renate C; Tegenthoff, Martin; Schwenkreis, Peter; Citak, Mustafa; Aach, Mirko

    2016-08-01

    Chronic neuropathic pain (CNP) is a common condition associated with spinal cord injury (SCI) and has been reported to be severe, disabling and often treatment-resistant and therefore remains a clinical challenge for the attending physicians. The treatment usually includes pharmacological and/or nonpharmacological approaches. Body weight supported treadmill training (BWSTT) and locomotion training with driven gait orthosis (DGO) have evolved over the last decades and are now considered to be an established part in the rehabilitation of SCI patients. Conventional locomotion training goes along with improvements of the patients' walking abilities in particular speed and gait pattern. The neurologic controlled hybrid assistive limb (HAL®, Cyberdyne Inc., Ibraki, Japan) exoskeleton, however, is a new tailored approach to support motor functions synchronously to the patient's voluntary drive. This report presents two cases of severe chronic and therapy resistant neuropathic pain due to chronic SCI and demonstrates the beneficial effects of neurologic controlled exoskeletal intervention on pain severity and health-related quality of life (HRQoL). Both of these patients were engaged in a 12 weeks period of daily HAL®-supported locomotion training. In addition to improvements in motor functions and walking abilities, both show significant reduction in pain severity and improvements in all HRQoL domains. Although various causal factors likely contribute to abatement of CNP, the reported results occurred due to a new approach in the rehabilitation of chronic spinal cord injury patients. These findings suggest not only the feasibility of this new approach but in conclusion, demonstrate the effectiveness of neurologic controlled locomotion training in the long-term management of refractory neuropathic pain. Implications for Rehabilitation CNP remains a challenge in the rehabilitation of chronic SCI patients. Locomotion training with the HAL exoskeleton seems to improve CNP

  12. Treatment Considerations for Elderly and Frail Patients With Neuropathic Pain

    OpenAIRE

    Schmader, Kenneth E.; Baron, Ralf; Haanpää, Maija L.; Mayer, John; O'Connor, Alec B.; Rice, Andrew S C; Stacey, Brett

    2010-01-01

    Currently, an estimated 38 million individuals 65 years or older live in the United States, and more than 11 million of these individuals are 80 years or older. Older people are at high risk of neuropathic pain because many diseases that cause neuropathic pain increase in incidence with age. Depending on their underlying health, older adults with neuropathic pain may have to cope with multiple coexisting diseases, polypharmacy, and impaired functional ability. The objective of this article is...

  13. PUNICA GRANATUM ATTENUATES SCIATIC NERVE LIGATION INDUCED-NEUROPATHIC PAIN

    OpenAIRE

    Ramica Sharma et al.

    2012-01-01

    The study has been designed to investigate the effect of aqueous extract of rind of Punica granatum in sciatic nerve ligation induced-neuropathic pain in rats. Surgical procedure was performed with sciatic nerve ligation to develop neuropathic pain in rats. The development of neuropathic pain was assessed by employing behaviour parameters such as hyperalgesia and allodynia. Further, the functionality of sciatic nerve was assessed using the histopathological study of myelinated and unmyelinate...

  14. TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States

    Directory of Open Access Journals (Sweden)

    Laura Batti

    2016-06-01

    Full Text Available Neuropathic pain is a widespread chronic pain state that results from injury to the nervous system. Spinal microglia play a causative role in the pathogenesis of neuropathic pain through secretion of growth factors and cytokines. Here, we investigated the contribution of TMEM16F, a protein that functions as a Ca2+-dependent ion channel and a phospholipid scramblase, to microglial activity during neuropathic pain. We demonstrate that mice with a conditional ablation of TMEM16F in microglia do not develop mechanical hypersensitivity upon nerve injury. In the absence of TMEM16F, microglia display deficits in process motility and phagocytosis. Moreover, loss of GABA immunoreactivity upon injury is spared in TMEM16F conditional knockout mice. Collectively, these data indicate that TMEM16F is an essential component of the microglial response to injury and suggest the importance of microglial phagocytosis in the pathogenesis of neuropathic pain.

  15. Low back pain - chronic

    Science.gov (United States)

    Nonspecific back pain; Backache - chronic; Lumbar pain - chronic; Pain - back - chronic; Chronic back pain - low ... Low back pain is common. Almost everyone has back pain at some time in their life. Often, the exact cause ...

  16. Anti-hyperalgesic effect of a benzilidine-cyclohexanone analogue on a mouse model of chronic constriction injury-induced neuropathic pain: Participation of the κ-opioid receptor and KATP.

    Science.gov (United States)

    Ming-Tatt, Lee; Khalivulla, Shaik Ibrahim; Akhtar, Muhammad Nadeem; Lajis, Nordin; Perimal, Enoch Kumar; Akira, Ahmad; Ali, Daud Israf; Sulaiman, Mohd Roslan

    2013-12-01

    The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.

  17. Non-invasive Brain Stimulation, a Tool to Revert Maladaptive Plasticity in Neuropathic Pain.

    Science.gov (United States)

    Naro, Antonino; Milardi, Demetrio; Russo, Margherita; Terranova, Carmen; Rizzo, Vincenzo; Cacciola, Alberto; Marino, Silvia; Calabro, Rocco S; Quartarone, Angelo

    2016-01-01

    Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of maladaptive plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions. PMID:27512368

  18. Treatment of neuropathic pain: a new method, transdermic route

    Directory of Open Access Journals (Sweden)

    Vittorio Iorno

    2006-05-01

    Full Text Available The therapy of neuropathic pain is difficult due to the lack of reliable classification. This pain can be defined as peripheral, central, mixed or based on the underlying mechanisms. Following this last criterium, we selected 44 patients affected by peripheral neuropathic pain. The not invasive care consisted in giving a pharmacological cocktail by a transdermal hydroelectrophoretic technique. 34% of all patients showed a pain relief between 70 and 99% (good results, while 9% had a complete resolution of pain (very good results. We concluded suggesting the transdermic hydroelectrophoretic techniques as useful and efficient in drugs administration to patients with peripheral neuropathic pain.

  19. Management of chronic musculoskeletal pain.

    Science.gov (United States)

    Uhl, Richard L; Roberts, Timothy T; Papaliodis, Dean N; Mulligan, Michael T; Dubin, Andrew H

    2014-02-01

    Chronic musculoskeletal pain results from a complex interplay of mechanical, biochemical, psychological, and social factors. Effective management is markedly different from that of acute musculoskeletal pain. Understanding the physiology of pain transmission, modulation, and perception is crucial for effective management. Pharmacologic and nonpharmacologic therapies such as psychotherapy and biofeedback exercises can be used to manage chronic pain. Evidence-based treatment recommendations have been made for chronic pain conditions frequently encountered by orthopaedic surgeons, including low back, osteoarthritic, posttraumatic, and neuropathic pain. Extended-release tramadol; select tricyclic antidepressants, serotonin reuptake inhibitors, and anticonvulsants; and topical medications such as lidocaine, diclofenac, and capsaicin are among the most effective treatments. However, drug efficacy varies significantly by indication. Orthopaedic surgeons should be familiar with the widely available safe and effective nonnarcotic options for chronic musculoskeletal pain. PMID:24486756

  20. Suppression of microRNA-155 attenuates neuropathic pain by regulating SOCS1 signalling pathway.

    Science.gov (United States)

    Tan, Yi; Yang, Jun; Xiang, Kai; Tan, Qindong; Guo, Qulian

    2015-03-01

    Chronic neuropathic pain is an unfavourable pathological pain characterised by allodynia and hyperalgesia which has brought considerable trouble to people's physical and mental health, but effective therapeutics are still lacking. MicroRNAs (miRNAs) have been widely studied in the development of neuropathic pain and neuronal inflammation. Among various miRNAs, miR-155 has been widely studied. It is intensively involved in regulating inflammation-associated diseases. However, the role of miR-155 in regulating neuropathic pain development is poorly understood. In the present study, we aimed to investigate whether miR-155 is associated with neuropathic pain and delineate the underlying mechanism. Using a neuropathic pain model of chronic constriction injury (CCI), miR-155 expression levels were markedly increased in the spinal cord. Inhibition of miR-155 significantly attenuated mechanical allodynia, thermal hyperalgesia and proinflammatory cytokine expression. We also demonstrated that miR-155 directly bound with the 3'-untranslated region of the suppressor of cytokine signalling 1 (SOCS1). The expression of SOCS1 significantly decreased in the CCI rat model, but this effect could be reversed by miR-155 inhibition. Furthermore, knockdown of SOCS1 abrogated the inhibitory effects of miR-155 inhibition on neuropathic development and neuronal inflammation. Finally, we demonstrated that inhibition of miR-155 resulted in the suppression of nuclear factor-κB and p38 mitogen-activated protein kinase activation by mediating SOCS1. Our data demonstrate the critical role of miR-155 in regulating neuropathic pain through SOCS1, and suggest that miR-155 may be an important and potential target in preventing neuropathic pain development. PMID:25488154

  1. Chronic pain - resources

    Science.gov (United States)

    Pain - resources; Resources - chronic pain ... The following organizations are good resources for information on chronic pain: American Chronic Pain Association -- www.theacpa.org National Fibromyalgia and Chronic Pain Association -- www.fmcpaware.org ...

  2. Chronic Pelvic Pain

    Science.gov (United States)

    ... Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  3. HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain.

    Science.gov (United States)

    Tsantoulas, Christoforos; Mooney, Elizabeth R; McNaughton, Peter A

    2016-09-15

    Nociception - the ability to detect painful stimuli - is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. Hyperpolarisation-activated cyclic nucleotide (HCN)-modulated ion channels are best known for their fundamental pacemaker role in the heart; here, we review data demonstrating that the HCN2 isoform acts in an analogous way as a 'pacemaker for pain', in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states. Pharmacological block or genetic deletion of HCN2 in sensory neurons provides robust pain relief in a variety of animal models of inflammatory and neuropathic pain, without any effect on normal sensation of acute pain. We discuss the implications of these findings for our understanding of neuropathic pain pathogenesis, and we outline possible future opportunities for the development of efficacious and safe pharmacotherapies in a range of chronic pain syndromes. PMID:27621481

  4. Prevalence of Neuropathic Pain and the Need for Treatment

    Directory of Open Access Journals (Sweden)

    Pat Morley-Forster

    2006-01-01

    There is an unmet need for the treatment of neuropathic pain as evidenced by reports of pain despite the use of opioids and anticonvulsants, continuing psychological difficulties, lack of access to treatments and patients seeking access to complementary therapy.

  5. Reduction of follistatin-like 1 in primary afferent neurons contributes to neuropathic pain hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Kai-Cheng Li; Feng Wang; Yan-Qing Zhong; Ying-Jin Lu; Qiong Wang; Fang-Xiong Zhang; Hua-Sheng Xiao; Lan Bao; Xu Zhang

    2011-01-01

    @@ Dear Editor, Nerve injury-induced neuropathic pain is difficult to treat in clinic.Lack of comprehensive understanding of the mechanism underlying such chronic pain hypersensitivity delays the development of more effective therapy.Accumulated evidence shows that peripheral nerve injury alters the expression of many neurotransmitters, receptors, ion channels and signaling molecules in the dorsal root ganglion (DRG) and the dorsal horn of spinal cord [1].Some of these molecular changes in the pain pathway are correlated with the current therapy for neuropathic pain.

  6. Effect of Gabapentin and Baclofen on Histology Study in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Fifteen A. Fajrin

    2015-12-01

    Full Text Available Neuropathic pain resulted from injury to nerves is often resistant to current treatments and can seriously cause chronic pain if no appropriate treatment is given. This study was designed to prove the effectiveness of gabapentin and baclofen in increasing latency time toward thermal stimulus and recovering the morphology of dorsal horn of spinal cord in neuropathic-induced chronic pain. Forty mice were divided into 8 groups i.e sham, negative control, gabapentin at three different doses (10, 30, 100 nmol and baclofen at three different doses (1, 10, 30 nmol. Neuropathic condition was induced by ligation of sciatic nerve with Partial Sciatic Nerve Ligation (PSNL method. Gabapentin and baclofen were administrated intrathecally once a day for seven days, a week after neuropathic induction. Latency time toward thermal stimulus was measured on days 0, 1, 3, 5, 7, 8, 10, 12 and 14 after induction. Histology of the dorsal horn of spinal cord tissue was examined by haematoxylline-eosin staining. The results showed that intrathecal injection of gabapentin and baclofen significantly increased latency time of mice toward thermal stimulus compared with negative control. Gabapentin and baclofen are effective as treatment for neuropathic pain. They can also help the recovery process of the histology in dorsal horn in neuropathic pain.

  7. Frequency, character, intensity and impact of neuropathic pain in a cohort of spinal cord injury patients

    International Nuclear Information System (INIS)

    The purpose of this study was to determine frequency, character, approximate location and intensity of neuropathic pain in spinal cord injury and its impact on the quality of life. Study Design: A cross-sectional survey Place and Duration of Study: Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi from Feb 2009 to Feb 2010. Material and Methods: Through non-probability convenience sampling 87 patients of both genders diagnosed with spinal cord injury based on American Spinal Injury Association criteria and admitted within a year of injury were included. Those in spinal shock, having poor cognition, inability to communicate, concurrent brain injury and history of chronic pain before injury were excluded. The history, localization and characteristics of the pain and interference with life activities were recorded. Neuropathic pain of patients was evaluated with Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale. Visual analogue scale was used to measure the severity of pain. Results: Out of 87 patients (mean age 36.9 years) seventy four were male and 13 were female. Seventy patients (80%) were AIS-A, 6 (7%) were AIS-B and 11 (13%) were AIS-C. Neuropathic pain was present in 57.5% (n=50). Most of the patients localized their pain below the neurological level of injury (78%) and rated pain intensity as moderate pain (54%). Majority (48%) described the pain as burning followed by electric shock like (42%), stabbing (8%) and pricking (2%). 48% patients reported that their quality of life was affected due to pain. 52% required two analgesics of different groups to relieve pain followed by 40% requiring three analgesics and 8% requiring one analgesic. Conclusion: Neuropathic pain is prevalent in people with spinal cord injury and adversely affects life quality. Neuropathic pain is primarily described as a burning sensation of moderate intensity mostly referred to below the neurological level of injury. (author)

  8. Neuropathic pain treatment: still a challenge

    Directory of Open Access Journals (Sweden)

    Osvaldo J.M. Nascimento

    2016-06-01

    Full Text Available Neuropathic pain (NP is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. We reviewed the published literature on the pharmacological treatment of NP. Despite the interesting results, randomized controlled trials are demanded the majority of the therapies previously mentioned. In spite of several studies for the relief of NP, pain control continues being a challenge.

  9. N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases.

    Science.gov (United States)

    Li, Jiajie; Xu, Lujie; Deng, Xueting; Jiang, Chunyi; Pan, Cailong; Chen, Lu; Han, Yuan; Dai, Wenling; Hu, Liang; Zhang, Guangqin; Cheng, Zhixiang; Liu, Wentao

    2016-08-01

    The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction of neural inflammation. Therefore, the inhibition of MMPs may represent a novel therapeutic approach to the treatment of neuropathic pain. In this study, we report that N-acetyl-cysteine (NAC), which is a broadly used respiratory drug, significantly attenuates neuropathic pain through a unique mechanism of MMP inhibition. Both the in vitro (0.1 mM) and in vivo application of NAC significantly suppressed the activity of MMP-9/2. Orally administered NAC (50, 100, and 200 mg/kg) not only postponed the occurrence but also inhibited the maintenance of chronic constrictive injury (CCI)-induced neuropathic pain in rats. The administration of NAC blocked the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppressed the neuronal activation induced by CCI, including inhibiting the phosphorylation of protein kinase Cγ, NMDAR1, and mitogen-activated protein kinases. Finally, NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain through the powerful inhibition of the activation of MMPs. PMID:27075430

  10. Characterizing neuropathic pain profiles: enriching interpretation of painDETECT

    Directory of Open Access Journals (Sweden)

    Cappelleri JC

    2016-07-01

    Full Text Available Joseph C Cappelleri,1 Vijaya Koduru,2 E Jay Bienen,3 Alesia Sadosky4 1Pfizer Inc, Groton, CT, USA; 2Eliassen Group, New London, CT, USA; 3Outcomes Research Consultant, New York, NY, USA; 4Pfizer Inc, New York, NY, USA Purpose: To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP, for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure. Methods: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine- and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into “at least moderate” (ie, moderate, strongly, very strongly relative to the combined other responses (never, hardly noticed, slightly. Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. Results: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score

  11. Employees with Chronic Pain

    Science.gov (United States)

    ... Home | Accommodation and Compliance Series: Employees with Chronic Pain By Beth Loy, Ph.D. Preface Introduction Information ... at http://AskJAN.org/soar. Information about Chronic Pain How prevalent is chronic pain? Chronic pain has ...

  12. Neuropathic pain referrals to a multidisciplinary pediatric cancer pain service.

    Science.gov (United States)

    Anghelescu, Doralina L; Faughnan, Lane G; Popenhagen, Mark P; Oakes, Linda L; Pei, Deqing; Burgoyne, Laura L

    2014-03-01

    Neuropathic pain (NP) in children with cancer is not well characterized. In a retrospective review of patient data from a 3.5-year period, we describe the prevalence of NP and the characteristics, duration of follow-up, and interventions provided for NP among patients referred to a pediatric oncology center's pain management service. Fifteen percent (66/439) of all referrals to our pain service were for NP (56/323 patients [17%]; 34 male, 22 female). The NP patient group had 1,401 clinical visits (778 inpatient visits [55.5%] and 623 outpatient visits [44.5%]). Patients with NP had a significantly greater mean number of pain visits per consultation (p = .008) and significantly more days of pain service follow-up (p cancer treatment rather than the underlying malignancy. Pharmacologic management of NP was complex, often comprising three medications. Nonpharmacologic approaches were used for 57.6% of NP referrals. Neuropathic pain is less frequently encountered than non-NP in children with cancer; nevertheless, it is more difficult to treat, requiring longer follow-up, more clinical visits, complex pharmacologic management, and the frequent addition of nonpharmacologic interventions.

  13. Complex Regional Pain Syndrome (CRPS/RSD and Neuropathic Pain: Role of Intravenous Bisphosphonates as Analgesics

    Directory of Open Access Journals (Sweden)

    Jennifer Yanow

    2008-01-01

    Full Text Available Neuropathic pain is a sequela of dysfunction, injuries, or diseases of the peripheral and/or central nervous system pain pathways, which has historically been extremely difficult to treat. Complex regional pain syndrome (CRPS types 1 and 2 are neuropathic pain conditions that have a long history in the medical literature but whose pathophysiology remains elusive and whose available treatment options remain few. While an exact animal model for CRPS doesn't yet exist, there are several animal models of neuropathic pain that develop behaviors of hypersensitivity, one of the hallmark signs of neuropathic pain in humans.

  14. [Capsaicin in treatment of neuropathic pain].

    Science.gov (United States)

    Kamchatnov, P R; Evzelman, M A; Abusueva, B A; Volkov, A I

    2014-01-01

    Treatment of neuropathic pain (NP) is a serious medical problem. Antiepileptic drugs and antidepressants, used to relief pain, act on the central pain mechanisms and cause several side-effects, thus substantially restricting possibilities of their clinical application.At the same time, NP often has a peripheral component. Ligand-associated channels, including vanilloid receptors TRPV1, play a key role in the development of regional NP syndromes. Capsaicin, a component of chili pepper and several other plants, is a highly selective ligand of TRPV1 receptors and has long been used in treatment of pain syndromes. However, its using is limited by short-term action and relatively low efficacy. Recently it has been shown that the local use of single high doses of capsaicin during 30-60 min causes a marked stable(> 12 weeks) effect. The decrease in NP (>50%) is seen in about half of patients. Current studies will allow to single out groups of patients with the maximal treatment effect of capsaicin. PMID:25629137

  15. Neuroimmunological mechanisms of chronic pain syndrome

    Directory of Open Access Journals (Sweden)

    I. A. Vyshlova

    2016-01-01

    Full Text Available The article considers the mechanisms of chronic low back pain. Three pathophysiological mechanisms: nociceptive, neurogenic (neuropathic, and psychogenic are noted to be involved in the development of pain syndrome. The role of cellular and molecular changes in the posterior horn and in the somatosensory dysregulated mechanism of neuropathic pain is shown. Immunological processes, including neurohumoral (serotoninergic and hormonal (sex hormones and specific proteins ones, play an important role in the development of pain. The generalization and further study of these mechanisms are embodied in approaches to therapy for pain syndromes and hence these require analysis and further investigation. 

  16. Studies on experimental and neuropathic orofacial pain, and low-dose ketamine as a probe for NMDA receptor function

    OpenAIRE

    2005-01-01

    The NMDA-receptor is known to play a central role in the development of acute andchronic pain. Ketamine is a clinically available NMDA-receptor inhibitor. We examined the role of the NMDA-receptor in acute experimental and chronic neuropathic orofacial pain in humans by using ketamine as a probe. We also examined pathophysiological mechanisms in patients suffering from orofacial neuropathic pain by use of quantitative sensory-testing. In a double-blind study we compared the effects of low...

  17. Can We Distinguish between Inflammatory and Neuropathic Pain?

    Directory of Open Access Journals (Sweden)

    Gary J Bennett

    2006-01-01

    Full Text Available Inflammatory and neuropathic pain were once considered to be distinct entities. However, research over the past decade or so has brought to light many shared mechanisms, and the distinction between the two is no longer clear. Consideration of mechanisms, symptoms and the effects of analgesic drugs does not reveal any definitive or universally applicable differentiating factors. Given the present level of understanding, it may not be possible to distinguish between inflammatory and neuropathic pain in a large number of patients, and a satisfying definition of neuropathic pain may not be possible.

  18. Intraoral administration of botulinum toxin for trigeminal neuropathic pain.

    Science.gov (United States)

    Herrero Babiloni, Alberto; Kapos, Flavia P; Nixdorf, Donald R

    2016-06-01

    This article presents 2 cases of different neuropathic trigeminal pain conditions treated with intraoral botulinum toxin injections. There is a growing body of evidence to support the use of this substance when administered subcutaneously in the treatment of neuropathic pain, such as in extraoral injections for trigeminal neuralgia. However, reports of intraoral submucosal administration are still lacking. In the 2 cases presented here, neuropathic pain was refractory to treatment with an important intraoral peripheral component, so onabotulinum toxin A was introduced as an adjuvant therapy. The technique, doses, and dilution are discussed. The patients reported significant reductions in pain frequency and intensity, with minimal side effects of temporary mucosal dryness and smile droopiness. The analgesic benefits of botulinum toxin may be utilized to address intraoral neuropathic pain. Further studies are needed to confirm safety and effectiveness in larger samples. PMID:27181448

  19. Diagnosis and medical treatment of neuropathic pain in leprosy 1

    Science.gov (United States)

    Arco, Rogerio Del; Nardi, Susilene Maria Tonelli; Bassi, Thiago Gasperini; Paschoal, Vania Del Arco

    2016-01-01

    ABSTRACT Objective: to identify the difficulties in diagnosing and treating neuropathic pain caused by leprosy and to understand the main characteristics of this situation. Methods: 85 patients were treated in outpatient units with reference to leprosy and the accompanying pain. We used a questionnaire known as the Douleur Neuropathic 4 test and we conducted detailed neurological exams. As a result, 42 patients were excluded from the study for not having proved their pain. Results: Out of the 37 patients that experienced pain, 22 (59.5%) had neuropathic pain (or a mixture of this pain and their existing pain) and of these 90.8% considered this pain to be moderate or severe. 81.8% of the sample suffered with this pain for more than 6 months. Only 12 (54.5%) of the patients had been diagnosed with neuropathic pain and in almost half of these cases, this pain had not been diagnosed. With reference to medical treatment (n=12) for neuropathic pain, 5 (41.6%) responded that they became better. For the other 7 (58.4%) there were no changes in relation to the pain or in some cases the pain worsened in comparison to their previous state. Statistical analysis comparing improvements in relation to the pain amongst the patients that were treated (n=12) and those that were not, showed significant differences (value p=0.020). Conclusion: we noted difficulties in diagnosing neuropathic pain for leprosy in that almost half of the patients that were studied had not had their pain diagnosed. We attributed this to some factors such as the non-adoption of the appropriate protocols which led to inadequate diagnosis and treatment that overlooked the true picture. PMID:27508904

  20. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain.

    Science.gov (United States)

    Moon, Young Eun; Choi, Jung Hyun; Park, Hue Jung; Park, Ji Hye; Kim, Ji Hyun

    2016-01-01

    Neuropathic pain includes postherpetic neuralgia (PHN), painful diabetic neuropathy (PDN), and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A) has been known for its analgesic effect in various pain conditions. Nevertheless, there are no data of nerve block in PHN and PDN. Here, we report two patients successfully treated with ultrasound-guided peripheral nerve block using BoNT-A for intractable PHN and PDN. One patient had PHN on the left upper extremity and the other patient had PDN on a lower extremity. Due to side effects of drugs, escalation of the drug dose could not be made. We injected 50 Botox units (BOTOX(®), Allergan Inc., Irvine, CA, USA) into brachial plexus and lumbar plexus, respectively, under ultrasound. Their pain was significantly decreased for about 4-5 months. Ultrasound-guided nerve block with BoNT-A may be an effective analgesic modality in a chronic intractable neuropathic pain especially when conventional treatment failed to achieve adequate pain relief. PMID:26761032

  1. Ultrasound-Guided Nerve Block with Botulinum Toxin Type A for Intractable Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Young Eun Moon

    2016-01-01

    Full Text Available Neuropathic pain includes postherpetic neuralgia (PHN, painful diabetic neuropathy (PDN, and trigeminal neuralgia, and so on. Although various drugs have been tried to treat neuropathic pain, the effectiveness of the drugs sometimes may be limited for chronic intractable neuropathic pain, especially when they cannot be used at an adequate dose, due to undesirable severe side effects and the underlying disease itself. Botulinum toxin type A (BoNT-A has been known for its analgesic effect in various pain conditions. Nevertheless, there are no data of nerve block in PHN and PDN. Here, we report two patients successfully treated with ultrasound-guided peripheral nerve block using BoNT-A for intractable PHN and PDN. One patient had PHN on the left upper extremity and the other patient had PDN on a lower extremity. Due to side effects of drugs, escalation of the drug dose could not be made. We injected 50 Botox units (BOTOX®, Allergan Inc., Irvine, CA, USA into brachial plexus and lumbar plexus, respectively, under ultrasound. Their pain was significantly decreased for about 4–5 months. Ultrasound-guided nerve block with BoNT-A may be an effective analgesic modality in a chronic intractable neuropathic pain especially when conventional treatment failed to achieve adequate pain relief.

  2. Neuropathic pain - the case for opioid therapy.

    Science.gov (United States)

    Allen, Stephen C

    2008-01-01

    For many patients, neuropathic pain (NeP) is arguably more difficult to control than nociceptive or 'normal' pain. We also now recognise the great burden that NeP has on the lives of patients - it is not only a matter of treating pain in isolation, but managing all of the issues that affect the patient's quality of life. Until relatively recently we have had little understanding of the pathophysiology causing NeP and have relied on the secondary effects of non-analgesic drugs as the mainstays of treatment. Greater understanding of the pathophysiology of NeP has led to more appropriate therapy and an increased use of multiple drug therapy - 'rational polypharmacy'. Traditional opinions concerning the treatment of NeP have been challenged and it is because of this that the use of opioids in NeP has been re-evaluated. Opioids will never replace tricyclic antidepressants and anti-epileptic drugs as first-line therapy for NeP. However, they are now fully established as effective and useful second- or third-line drugs. Many patients in the past have been potentially undertreated as a result of our inertia to use opioids. The case for opioid therapy in NeP has been firmly established. PMID:18758203

  3. Neuropathic cancer pain: What we are dealing with? How to manage it?

    Science.gov (United States)

    Esin, Ece; Yalcin, Suayib

    2014-01-01

    Cancer pain is a serious health problem, and imposes a great burden on the lives of patients and their families. Pain can be associated with delay in treatment, denial of treatment, or failure of treatment. If the pain is not treated properly it may impair the quality of life. Neuropathic cancer pain (NCP) is one of the most complex phenomena among cancer pain syndromes. NCP may result from direct damage to nerves due to acute diagnostic/therapeutic interventions. Chronic NCP is the result of treatment complications or malignancy itself. Although the reason for pain is different in NCP and noncancer neuropathic pain, the pathophysiologic mechanisms are similar. Data regarding neuropathic pain are primarily obtained from neuropathic pain studies. Evidence pertaining to NCP is limited. NCP due to chemotherapeutic toxicity is a major problem for physicians. In the past two decades, there have been efforts to standardize NCP treatment in order to provide better medical service. Opioids are the mainstay of cancer pain treatment; however, a new group of therapeutics called coanalgesic drugs has been introduced to pain treatment. These coanalgesics include gabapentinoids (gabapentin, pregabalin), antidepressants (tricyclic antidepressants, duloxetine, and venlafaxine), corticosteroids, bisphosphonates, N-methyl-D-aspartate antagonists, and cannabinoids. Pain can be encountered throughout every step of cancer treatment, and thus all practicing oncologists must be capable of assessing pain, know the possible underlying pathophysiology, and manage it appropriately. The purpose of this review is to discuss neuropathic pain and NCP in detail, the relevance of this topic, clinical features, possible pathology, and treatments of NCP.

  4. Minociclyne, microglia and neuropathic pain (Minociclina, microglia e dolore neuropatico

    Directory of Open Access Journals (Sweden)

    Maria Luisa Sotgiu

    2014-03-01

    Full Text Available An update on minocicline properties with particular focus on its effect on the microglia activation and on a possible therapeutic utilization as analgesic in neuropathic pain is presented.

  5. Contribution of interleukin-1beta in neuropathic pain

    Directory of Open Access Journals (Sweden)

    GUO Wei

    2013-09-01

    Full Text Available Interleukin-1beta (IL-1β, a pro-inflammatory cytokine, has been implicated in the development of peripheral and central sensitization that is charactistic of neuropathic pain. Recent studies demonstrated that IL-1β is an important messenger that is interacted with glia and neurons in the central neurous system in the neuropathic pain states. Some new studies showed that IL-1β activation was regulated by several other cytokines such as CCL2, MMP-2 and MMP-9 during the neuropathic pain conditions. This review will briefly describe the key role of IL-1 β and its signaling contributes to the peripheral and central nervous system in the neuropathic pain.

  6. Dynamics of circadian thalamocortical flow of information during a peripheral neuropathic pain condition

    Directory of Open Access Journals (Sweden)

    Helder eCardoso-Cruz

    2011-08-01

    Full Text Available It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials – LFPs – both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence – PDC – analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and slow-wave-sleep episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  7. Dynamics of Circadian Thalamocortical Flow of Information during a Peripheral Neuropathic Pain Condition.

    Science.gov (United States)

    Cardoso-Cruz, Helder; Sameshima, Koichi; Lima, Deolinda; Galhardo, Vasco

    2011-01-01

    It is known that the thalamocortical loop plays a crucial role in the encoding of sensory-discriminative features of painful stimuli. However, only a few studies have addressed the changes in thalamocortical dynamics that may occur after the onset of chronic pain. Our goal was to evaluate how the induction of chronic neuropathic pain affected the flow of information within the thalamocortical loop throughout the brain states of the sleep-wake cycle. To address this issue we recorded local field potentials (LFPs) - both before and after the establishment of neuropathic pain in awake freely moving adult rats chronically implanted with arrays of multielectrodes in the lateral thalamus and primary somatosensory cortex. Our results show that the neuropathic injury induced changes in the number of wake and slow-wave-sleep (SWS) state episodes, and especially in the total number of transitions between brain states. Moreover, partial directed coherence - analysis revealed that the amount of information flow between cortex and thalamus in neuropathic animals decreased significantly, indicating that the overall thalamic activity had less weight over the cortical activity. However, thalamocortical LFPs displayed higher phase-locking during awake and SWS episodes after the nerve lesion, suggesting faster transmission of relevant information along the thalamocortical loop. The observed changes are in agreement with the hypothesis of thalamic dysfunction after the onset of chronic pain, and may result from diminished inhibitory effect of the primary somatosensory cortex over the lateral thalamus.

  8. Involvement of phosphatase and tensin homolog deleted from chromosome 10 in rodent model of neuropathic pain

    OpenAIRE

    Huang, Shi-Ying; Sung, Chun-Sung; Chen, Wu-Fu; Chen, Chun-Hong; Feng, Chien-Wei; Yang, San-Nan; Hung, Han-Chun; Chen, Nan-Fu; Lin, Pey-Ru; Chen, San-Cher; Wang, Hui-Min David; Chu, Tian-Huei; Tai, Ming-Hong; Wen, Zhi-Hong

    2015-01-01

    Background Many cancer research studies have extensively examined the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway. There are only few reports that suggest that PTEN might affect pain; however, there is still a lack of evidence to show the role of PTEN for modulating pain. Here, we report a role for PTEN in a rodent model of neuropathic pain. Results We found that chronic constriction injury (CCI) surgery in rats could elicit downregulation of spinal PTEN as well a...

  9. Use of naturally occurring peptides for neuropathic spinal cord injury pain.

    Science.gov (United States)

    Hama, Aldric; Sagen, Jacqueline

    2013-05-01

    Spinal cord injury (SCI) is accompanied by intractable pain as well as loss of motor and visceral control. As part of an overall strategy in patient rehabilitation and improvement in quality of life, pain management is crucial. Interestingly, SCI patients report pain below the level of injury that has characteristics of neuropathic-type pain. Preclinical studies suggest that a key substrate that underlies the symptoms of neuropathic pain such as spontaneous pain and below-level cutaneous hypersensitivity is aberrant activity of spinal dorsal horn neurons. While pharmacotherapies for peripheral neuropathic pain exist, these treatments may lead to adverse side effects in SCI patients, such as muscle weakness and constipation, which may exacerbate existing dysfunctions. Thus, novel therapeutic strategies are needed. One way to limit the adverse effects associated with systemically administered drugs is intrathecal delivery. Intrathecal delivery also directs drug to dorsal horn neurons. Another way to reduce the severity of side effects and to potentially enhance drug efficacy is to utilize combination drug therapy. While the conopeptide ziconotide has demonstrated clinical efficacy for severe chronic pain, a limitation of this drug is its potential for significant side effects. Combinations of conopeptides with currently available drugs as well as with other conopeptides could be an effective means of reducing neuropathic SCI pain. PMID:23721309

  10. Human surrogate models of neuropathic pain: validity and limitations.

    Science.gov (United States)

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  11. PUNICA GRANATUM ATTENUATES SCIATIC NERVE LIGATION INDUCED-NEUROPATHIC PAIN

    Directory of Open Access Journals (Sweden)

    Ramica Sharma et al.

    2012-02-01

    Full Text Available The study has been designed to investigate the effect of aqueous extract of rind of Punica granatum in sciatic nerve ligation induced-neuropathic pain in rats. Surgical procedure was performed with sciatic nerve ligation to develop neuropathic pain in rats. The development of neuropathic pain was assessed by employing behaviour parameters such as hyperalgesia and allodynia. Further, the functionality of sciatic nerve was assessed using the histopathological study of myelinated and unmyelinated fibers in sciatic nerve. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS, catalase, glutathione and tissue TBARS and Superoxide dismutase (SOD. Rats exposed to sciatic nerve ligation produced marked increase in oxidative stress, which was assessed in terms of TBARS and SOD along with decrease in the level of catalase and glutathione. Moreover, it develops neuropathic pain by impairing the normal functions of myelinated and unmyelinated fibers in sciatic nerve. Treatment with aqueous extract of Punica granatum extract (100mg/kg, p.o markedly prevented sciatic nerve ligation-induced neuropathy and oxidative stress by increasing the pain threshold, by improving the functionality of sciatic nerve, by decreasing serum and tissue TBARS and tissue SOD, by increasing levels of serum glutathione and catalase. It may be concluded that Punica granatum extract reduced the oxidative stress via inhibiting p38MAPK and alleviates neuropathic symptoms and consequently improved the functionality of sciatic nerve and prevents sciatic nerve ligation–induced neuropathic pain.

  12. pain2: A neuropathic pain QTL identified on rat chromosome 2.

    Science.gov (United States)

    Nissenbaum, Jonathan; Shpigler, Hagai; Pisanté, Anne; DelCanho, Sonia; Minert, Anne; Seltzer, Ze'ev; Devor, Marshall; Darvasi, Ariel

    2008-03-01

    We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus) based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus musculus). The work was based on rat selection lines HA (high autotomy) and LA (low autotomy) which show a contrasting pain phenotype in response to nerve injury in the neuroma model of neuropathic pain. An F(2) segregating population was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on chromosome 7 and chromosome 2, regions that share a partial homology with mouse chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63 (corresponding to p=0.005 after correcting for multiple testing using permutations) on rat chromosome 2, which is suggestive of the presence of a QTL affecting the predisposition to neuropathic pain. This QTL was mapped to the 14-26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse chromosome 13, rather than to the region of mouse chromosome 15 that contains pain1. This chromosomal position indicates that it is possibly a new QTL, and hence we name it pain2. Further work is needed to replicate and to uncover the underlying gene(s) in both species.

  13. Elucidation of pathophysiology and treatment of neuropathic pain.

    Science.gov (United States)

    Vranken, Jan H

    2012-12-01

    Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that would be the basis of underlying neuropathic pain mechanism. Additionally, neuro-imaging (positron emission tomography and functional magnetic resonance imaging) provides insights in brain mechanisms corresponding with mechanistic processes including allodynia, hyperalgesia, altered sensation, and spontaneous pain. A change in function, chemistry, and structures of neurons (neural plasticity) underlie the production of the altered sensitivity characteristics of neuropathic pain. Peripheral processes in neuropathic pain involve production of mediators (cytokines, protons, nerve growth factor), alterations in calcium channels, sodium channels, hyperpolarisation-activated nucleotide-gated ion channels, and potassium channels, phenotypic switches and sprouting of nerves endings, and involvement of the sympathetic nervous system. Stimulation of the N-Methyl-D-Aspartate receptor, activation of microglia, oligodendrocytes, and astrocytes, increased production of nerve growth factor and brain-derived neurotrophic factor together with loss of spinal inhibitory control are responsible for central neuron hyperexcitability and maintenance of neuropathic pain. Recent advances, including functional imaging techniques, in identification of peripheral and central sensitization mechanisms related to nervous system injury have increased potential for affecting pain research from both diagnostic as well as therapeutic view. Key brain regions involved in generating pharmacologically induced analgesia may be identified. Despite the progress in pain research, neuropathic pain is challenge to manage. Although numerous treatment options are available for relieving neuropathic pain, there is no

  14. Methylcobalamin ameliorates neuropathic pain induced by vincristine in rats

    Science.gov (United States)

    Xu, Jing; Wang, Wei; Zhong, Xiong-Xiong; Feng, Yi-Wei; Liu, Xian-Guo

    2016-01-01

    Background Vincristine, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and there are currently no effective drugs to prevent or treat this side effect. Previous studies have shown that methylcobalamin has potential analgesic effect in diabetic and chronic compression of dorsal root ganglion model; however, whether methylcobalamin has effect on vincristine-induced painful peripheral neuropathy is still unknown. Results We found that vincristine-induced mechanical allodynia and thermal hyperalgesia, accompanied by a significant loss of intraepidermal nerve fibers in the plantar hind paw skin and an increase in the incidence of atypical mitochondria in the sciatic nerve. Moreover, in the spinal dorsal horn, the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the protein expression of p-p65 as well as tumor necrosis factor α was increased, whereas the protein expression of IL-10 was decreased following vincristine treatment. Furthermore, intraperitoneal injection of methylcobalamin could dose dependently attenuate vincristine-induced mechanical allodynia and thermal hyperalgesia, which was associated with intraepidermal nerve fibers rescue, and atypical mitochondria prevalence decrease in the sciatic nerve. Moreover, methylcobalamin inhibited the activation of NADPH oxidase and the downstream NF-κB pathway. Production of tumor necrosis factor α was also decreased and production of IL-10 was increased in the spinal dorsal horn following methylcobalamin treatment. Intrathecal injection of Phorbol-12-Myristate-13-Acetate, a NADPH oxidase activator, could completely block the analgesic effect of methylcobalamin. Conclusions Methylcobalamin attenuated vincrinstine-induced neuropathic pain, which was accompanied by inhibition of intraepidermal nerve fibers loss and mitochondria impairment. Inhibiting the activation of NADPH oxidase and the downstream NF-κB pathway, resulting in the rebalancing of

  15. [Exploration of novel therapeutic targets for neuropathic pain based on the regulation of immune cells].

    Science.gov (United States)

    Kobayashi, Yuka; Kiguchi, Norikazu; Saika, Fumihiro; Kishioka, Shiroh

    2015-06-01

    The pathogenesis of neuropathic pain is quite complicated and diverse. Because pre-existing analgesics, such as opioid analgesics and nonsteroidal anti-inflammatory drugs, are not sufficient to treat it, it is a serious task to establish a strategy of remedy for neuropathic pain. Recently, increasing evidence suggests that immune cell-mediated neuroinflammation in the nervous system induces central and peripheral sensitization, resulting in chronic pain. Initially, the immune system plays an important role in host defense. Although intravital homeostasis is kept constant by innate and adaptive immunity, the immune system is activated excessively due to infection, stress and tissue injury. Activated immune cells produce and release several kinds of inflammatory mediators, which act directly on sensory neurons and promote a recruitment of immune cells, developing the feedback loop of inflammatory exacerbation. We've focused on the role of crosstalk between immune cells and neurons in peripheral neuroinflammation, and explored a novel candidate for a remedy of neuropathic pain. In this review, we will introduce recent reports and our research work that suggest the functional significance of neuroinflammation in neuropathic pain, and survey possibilities of new strategies for chronic pain from the point of view of basic research. PMID:26281298

  16. EFNS guidelines on pharmacological treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Attal, Nadine; Cruccu, G; Haanpää, M;

    2006-01-01

    for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal...... neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too...

  17. Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Fei-xiang Wu, Jin-jun Bian, Xue-rong Miao, Sheng-dong Huang, Xue-wu Xu, De-jun Gong, Yu-ming Sun, Zhi-jie Lu, Wei-feng Yu

    2010-01-01

    Full Text Available Background: Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG, spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4 might play a role in neuropathic pain. Methodology/Principal Findings: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-κB p65 and production of proinflammatory cytokines (e.g., TNF-α and IL-1β. Conclusions/Significance: These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

  18. The Christchurch Earthquake: Crush Injury, Neuropathic Pain, and Posttraumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Frances Cammack

    2013-01-01

    Full Text Available On February 22, 2011, an earthquake of magnitude 6.3 struck Christchurch, New Zealand. The peak ground acceleration, a measure of the shaking or intensity of an earthquake, was one of the highest ever recorded worldwide. One hundred and eighty-five people lost their lives; many others were injured. Two cases both involving young women are presented; they sustained crush injuries to limbs after being trapped by falling debris and went on to develop severe neuropathic pain. This report examines the mechanisms of neuropathic pain in the setting of crush injury, the treatment modalities, and the association between chronic pain and posttraumatic stress disorder. These case reports highlight the fact that crush injury is relatively common during major earthquakes and that neuropathic pain is an important sequel of this. Post-traumatic stress disorder is common in earthquake survivors with a recognised association with chronic pain. Pain-related disability may increase as well. Issues such as chronic pain and physical disability should not be overlooked as attention focuses on disaster management and the treatment of life-threatening injuries.

  19. Duloxetine in the management of diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Boomershine CS

    2011-07-01

    Full Text Available Michelle J Ormseth, Beth A Sholz, Chad S BoomershineDivision of Rheumatology and Immunology, Vanderbilt University, Nashville, TN, USAAbstract: Diabetic neuropathy affects up to 70% of diabetics, and diabetic peripheral neuropathic pain (DPNP is the most common and debilitating of the diabetic neuropathies. DPNP significantly reduces quality of life and increases management costs in affected patients. Despite the impact of DPNP, management is poor with one-quarter of patients receiving no treatment and many treated with medications having little or no efficacy in managing DPNP. Duloxetine is one of two drugs approved by the United States Food and Drug Administration for DPNP management. Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI proven safe, effective, and cost-saving in reducing DPNP symptoms at a dose of 60 mg/day. Duloxetine doses greater than 60 mg/day for DPNP management are not recommended since they are no more efficacious and associated with more side effects; addition of pregabalin or gabapentin for these patients may be beneficial. Side effects of duloxetine are generally mild and typical for the SNRI class including nausea, dizziness, somnolence, fatigue, sweating, dry mouth, constipation, and diarrhea. Given its other indications, duloxetine is a particularly good choice for DPNP treatment in patients with coexisting depression, anxiety, fibromyalgia, or chronic musculoskeletal pain. Duloxetine treatment had no clinically significant effect on glycemic control and did not increase the risk of cardiovascular events in diabetes patients. However, duloxetine use should be avoided in patients with hepatic disease or severe renal impairment. Given its safety, efficacy, and tolerability, duloxetine is an excellent choice for DPNP treatment in many patients.Keywords: duloxetine, diabetic peripheral neuropathic pain, review, treatment

  20. Transforming growth factor-β1 impairs neuropathic pain through pleiotropic effects

    OpenAIRE

    Liu Hong; Haw Alexandra; Shi Xiang; Echeverry Stefania; Zhang Zhong-wei; Zhang Ji

    2009-01-01

    Abstract Background Understanding the underlying mechanisms of neuropathic pain caused by damage to the peripheral nervous system remains challenging and could lead to significantly improved therapies. Disturbance of homeostasis not only occurs at the site of injury but also extends to the spinal cord and brain involving various types of cells. Emerging data implicate neuroimmune interaction in the initiation and maintenance of chronic pain hypersensitivity. Results In this study, we sought t...

  1. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Programs Resource Guide to Chronic Pain Treatments Pain Awareness Toolkits Partners for Understanding Pain September is Pain Awareness Month Home Pain Management Tools Videos What Is ...

  2. The effect of Sativex in neuropathic pain and spasticity in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Hansen, Rikke Bod Middelhede; Johansen, Inger Lauge;

    2014-01-01

    Introduction: Neuropathic pain and spasticity after spinal cord injury represent significant but still unresolved problems, which cause considerable suffering and reduced quality of life for patients with spinal cord injury. Treatment of neuropathic pain and spasticity is complicated and patients...

  3. Pain relief induces dopamine release in the rat nucleus accumbens during the early but not late phase of neuropathic pain.

    Science.gov (United States)

    Kato, Takahiro; Ide, Soichiro; Minami, Masabumi

    2016-08-26

    Comorbidity of chronic pain and depression has long been recognized in the clinic, and preclinical studies have reported depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for chronic pain and depression. The neuronal pathway from the ventral tegmental area to the nucleus accumbens (NAc) is critical in the mesolimbic dopamine (DA) reward circuit, and dysfunction of this pathway has been implicated in depression. Although time-dependent development of depression-related behaviors has been reported in chronic pain animals, time-dependent functional changes in this pathway remain to be examined. To address this issue, we examined the effects of two types of rewards, pain relief by intrathecal injection of pregabalin (100μg in 10μL phosphate buffered saline) and 30% sucrose solution intake, on intra-NAc DA release in rats subjected to spinal nerve ligation (SNL). Specifically, the effects were investigated during the early (17-20days after ligation) and late (31-34days after ligation) phases of neuropathic pain. Pain relief increased the intra-NAc DA levels in the SNL rats during the early but not late phase of neuropathic pain. Intake of the sucrose solution increased the intra-NAc DA levels both in the SNL and sham animals during the early phase of neuropathic pain, while it induced DA release in the sham but not SNL animals during the late phase. These results suggest that dysfunction of the mesolimbic DA reward circuit develops in a time-dependent manner. Mesolimbic DA reward circuit dysfunction might be a common neuronal mechanism underlying chronic pain and depression, and a potential target for novel analgesic and antidepressant medications. PMID:27369326

  4. Neuropathic Pain Model of Peripheral Neuropathies Mediated by Mutations of Glycyl-tRNA Synthetase

    OpenAIRE

    Lee, Seo Jin; Seo, Ah Jung; Park, Byung Sun; Jo, Hyun Woo; Huh, Youngbuhm

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. Previous studies have found that, according to CMT patients, neuropathic pain is an occasional symptom of CMT. However, neuropathic pain is not considered to be a significant symptom associated with CMT and, as a result, no studies have investigated the pathophysiology underlying neuropathic pain in this disorder. Thus, the first animal model of neuropathic pain was developed by our laboratory using a...

  5. Expectations and positive emotional feelings accompany reductions in ongoing and evoked neuropathic pain following placebo interventions.

    Science.gov (United States)

    Petersen, Gitte L; Finnerup, Nanna B; Grosen, Kasper; Pilegaard, Hans K; Tracey, Irene; Benedetti, Fabrizio; Price, Donald D; Jensen, Troels S; Vase, Lene

    2014-12-01

    Research on placebo analgesia and nocebo hyperalgesia has primarily included healthy subjects or acute pain patients, and it is unknown whether these effects can be obtained in ongoing pain in patients with chronic pain caused by an identifiable nerve injury. Eighteen patients with postthoracotomy neuropathic pain were exposed to placebo and nocebo manipulations, in which they received open and hidden administrations of pain-relieving (lidocaine) or pain-inducing (capsaicin) treatment controlled for the natural history of pain. Immediately after the open administration, patients rated their expected pain levels on a mechanical visual analogue scale (M-VAS). They also reported their emotional feelings via a quantitative/qualitative experiential method. Subsequently, patients rated their ongoing pain levels on the M-VAS and underwent quantitative sensory testing of evoked pain (brush, pinprick, area of hyperalgesia, wind-up-like pain). There was a significant placebo effect on both ongoing (P=.009 to .019) and evoked neuropathic pain (P=.0005 to .053). Expected pain levels accounted for significant amounts of the variance in ongoing (53.4%) and evoked pain (up to 34.5%) after the open lidocaine administration. Furthermore, patients reported high levels of positive and low levels of negative emotional feelings in the placebo condition compared with the nocebo condition (P⩽.001). Pain increases during nocebo were nonsignificant (P=.394 to 1.000). To our knowledge, this is the first study to demonstrate placebo effects in ongoing neuropathic pain. It provides further evidence for placebo-induced reduction in hyperalgesia and suggests that patients' expectations coexist with emotional feelings about treatments.

  6. Acupuncture effects on the hippocampal cholinergic system in a rat model of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Junying Wang; Junling Liu; Shuping Chen; Yonghui Gao; Fanying Meng; Lina Qiao

    2012-01-01

    The present study observed the effects of repeated electroacupuncture of Zusanli (ST36) and Yanglingquan (GB34) on expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA in chronic constrictive injury (neuropathic pain) and/or ovariotomy rats. Results demonstrated increased expression of hippocampal acetylcholinesterase, vesicular acetylcholine transporter, and muscarinic M1 receptor mRNA, as well as decreased pain threshold, in a rat model of chronic neuropathic pain after electroacupuncture. The effects of electroacupuncture increased with prolonged time, but the above-mentioned effects decreased in memory-deficient animals. Results indicated that repeated electroacupuncture has a cumulative analgesic effect, which is closely associated with upregulation of acetylcholinesterase and vesicular acetylcholine transporter activity, as well as M1 receptor mRNA expression and memory.

  7. Stress Exacerbates Neuropathic Pain via Glucocorticoid and NMDA Receptor Activation

    OpenAIRE

    Alexander, Jessica K.; DeVries, A Courtney; KIGERL, KRISTINA A.; Dahlman, Jason M.; G.Popovich, Phillip

    2009-01-01

    There is growing recognition that psychological stress influences pain. Hormones that comprise the physiological response to stress (e.g. corticosterone; CORT) may interact with effectors of neuropathic pain. To test this hypothesis, mice received a spared nerve injury (SNI) after exposure to 60 min restraint stress. In stressed mice, allodynia was consistently increased. The mechanism(s) underlying the exacerbated pain response involves CORT acting via glucocorticoid receptors (GRs); RU486, ...

  8. Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain

    DEFF Research Database (Denmark)

    Andresen, Sven R; Bing, Jette; Hansen, Rikke M;

    2016-01-01

    This randomized controlled trial found no effect of ultramicronized palmitoylethanolamide as add-on-therapy on neuropathic pain after spinal cord injury.Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide t.......4 (-0.1 to 0.9) vs 0.7 (0.2 to 1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo....

  9. Untying chronic pain

    OpenAIRE

    Häuser, Winfried; Wolfe, Frederik; Henningsen, Peter; Schmutzer, Gabriele; Brähler, Elmar; Hinz, Andreas

    2014-01-01

    Background: Chronic pain is a major public health problem. The impact of stages of chronic pain adjusted for disease load on societal burden has not been assessed in population surveys. Methods: A cross-sectional survey with 4360 people aged ≥ 14 years representative of the German population was conducted. Measures obtained included demographic variables, presence of chronic pain (based on the definition of the International Association for the Study of Pain), chronic pain stages (by chronic ...

  10. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  11. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B; Nikolajsen, L; Kehlet, Henrik;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...

  12. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... Contact Us Shop FAQs The Art of Pain Management Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to Chronic Pain Treatments Pain ...

  13. What Is Chronic Pain?

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    Full Text Available Already a member? Log In or Sign Up Home About Us Support the ACPA Contact Us Shop ... for Understanding Pain September is Pain Awareness Month Home Pain Management Tools Videos What Is Chronic Pain? ...

  14. A burden of illness study for neuropathic pain in Europe

    Directory of Open Access Journals (Sweden)

    Liedgens H

    2016-04-01

    countries: €7,098 in France, €11,232 in Germany, €6,382 in Italy, €7,066 in Spain, and €5,492 in the UK. In the subgroup analysis, total annual direct costs per patient were highest for neuropathic back pain and radiculopathy, and lowest for fibromyalgia. Mean WPAI score range was 34.4–56.1; BPI interference was 4.1–4.8; and EQ-5D was 0.57–0.74. The results suggest that a significant proportion of the patient's work time in the previous week was affected by NP, and these are relatively high compared with other diseases such as diabetes, respiratory conditions, and arthritis. Implications: Despite differences in practice between countries, these findings suggest a high opportunity cost for society in terms of lost work and productivity due to NP. The wider costs appear significantly higher to patients, carers/families, and society as a whole than to the health system alone. Keywords: neuropathic pain, burden of illness, chronic lower back pain, productivity

  15. Botulinum toxin - neuropathic pain: Safety and efficacy of repeated injections of botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    2016-08-12

    When treated with botulinum toxin A, those patients with peripheral neuropathic pain and allodynia (triggering of pain from stimuli which do not normally provoke pain) at baseline, would appear to have a better outcome. PMID:27514345

  16. The painDETECT project - far more than a screening tool on neuropathic pain.

    Science.gov (United States)

    Freynhagen, Rainer; Tölle, Thomas R; Gockel, Ulrich; Baron, Ralf

    2016-06-01

    Background and objectives The painDETECT questionnaire (PD-Q), a simple and reliable screening questionnaire of neuropathic pain, was developed in 2004 in cooperation with the German Research Network on Neuropathic Pain. The initial aim was to implement quality management and to improve the situation of neuropathic pain (NeP) patients in Germany. The PD-Q proved immediately successful and was translated into and validated in multiple languages. Subsequently a comprehensive electronic system (PD) comprising various validated questionnaires with regard to pain typical comorbidities, such as function, sleep, mood or anxiety, was implemented Germany wide. We aimed to provide a comprehensive overview about the development and validation as well as the application of the PD-Q in various clinical conditions. Methods This overview is based on a literature search on English full-text papers using the term 'painDETECT' in Medline and PubMed covering the time period from 2006 to September 2015, amended with further publications cited in the retrieved publications or provided by the questionnaire developers. Results PD-Q as screening tool for NeP described in patients with lower back pain (8 studies), rheumatoid arthritis and osteoarthritis (10), thoracotomy (2 studies), tumor diseases (4 studies), fibromyalgia (4 studies), diverse musculoskeletal conditions (12 studies) and diverse other conditions (10 studies). In addition, the PD-Q was used in 9 studies that investigated the effect of drugs for the treatment of patients with a NeP component. Conclusion To date more than 300,000 patients were assessed, providing the basis for one of the world's largest datasets for chronic pain. Among others the extensive pool of PD-Q data triggered the idea of subgrouping patients on the basis of their individual sensory profiles which might in the future lead to a stratified treatment approach and ultimately to personalized therapy. Started as a healthcare utilization project in Germany

  17. Neuropathic Pain Following Spinal Cord Injury: Mechanism, Assessment and Treatment

    Directory of Open Access Journals (Sweden)

    Gul Mete Civelek

    2016-04-01

    Full Text Available Spinal cord injury (SCI is a devastating disease which may cause physical, psychological and social dysfunction. Neuropathic pain (NP after SCI is common, can be seen in varying degrees and is one of the most difficultly treated problems developing after SCI. With the addition of the NP to loss of function after SCI, sleep patterns, moods and daily activities of patients are adversely affected. In order to treat pain effectively, classification of pain after SCI must be done carefully and correctly. According to classification of International Pain Study Group, pain after SCI is divided into two main groups as nociceptive and neuropathic pain. Neuropathic pain is defined as %u201Cpain occuring as a direct result of a disease or lesion directly affecting somato-sensorial system%u201D. NP after SCI can be classified according to anatomical region (above the level of lesion, at the level of lesion, below the level of lesion. Treatment of NP after SCI is often challenging and receiving response to treatment may take long time. Therefore, treatment of NP after SCI should be multifactorial. Treatment options include pharmochologic treatment, application of transcutanous electrical nerve stimulation, psychiatric treatment approaches, and surgical approaches in selected cases. In pharmachologic treatment, first line agents are tricyclic antidepresants, pregabalin and gabapentin. In this review, mechanisms and assessment and treatment of NP after SCI is discussed with the guide of current literature.

  18. Pain relief with lidocaine 5% patch in localized peripheral neuropathic pain in relation to pain phenotype

    DEFF Research Database (Denmark)

    Demant, Dyveke T; Lund, Karen; Finnerup, Nanna B;

    2015-01-01

    periods of lidocaine 5% patch and placebo was performed to search for phenotype differences in effect. The primary efficacy measure was the total pain intensity on an 11-point numeric rating scale (NRS), and the primary objective was to compare the effect of lidocaine in patients with and without...... had an effect on peripheral neuropathic pain, and it may be most efficacious in patients with irritable nociceptor phenotype. The lack of significant phenotype differences may be caused by too low statistical power.......In neuropathic pain with irritable nociceptor phenotype, up-regulation of sodium channels on nociceptors is supposed to be an important pain mechanism that may be targeted by topical sodium channel blockade. This randomised, double-blind, phenotype-panel, cross-over study with 4-week treatment...

  19. Lateral Hypothalamic Stimulation Reduces Hyperalgesia Through Spinally Descending Orexin-A Neurons in Neuropathic Pain.

    Science.gov (United States)

    Wardach, Jacob; Wagner, Monica; Jeong, Younhee; Holden, Janean E

    2016-03-01

    No evidence to date shows that lateral hypothalamic (LH) stimulation produces orexin-A-mediated antinociception in the spinal cord dorsal horn (SCDH) in a model of neuropathic pain. We conducted experiments to examine the effect of orexin-A-mediated LH stimulation in female rats with chronic constriction injury (CCI) on thermal hyperalgesia. Rats receiving carbachol into the LH demonstrated antinociception on both the left CCI and right nonligated paws (p < .05). Rats were given carbachol in the LH followed by intrathecal injection of the orexin-1 (OX1) receptor antagonist SB-334867, which blocked LH-induced antinociception compared with control groups (p < .05) in the left paw, but not in the right paw. These findings support the hypothesis that LH stimulation produces antinociception in rats with thermal hyperalgesia from neuropathic pain via an orexin-A connection between the LH and the SCDH. Identification of this pathway may lead to studies using orexins to manage clinical pain.

  20. Walking with Neuropathic Pain: Paradoxical Shift from Burden to Support?

    Directory of Open Access Journals (Sweden)

    David J. Kopsky

    2015-01-01

    Full Text Available Baclofen 5% cream can be used for the treatment of neuropathic pain. We describe an unusual case of a neuropathic pain patient with spinal cord injury. A 71-year-old woman with a partial spinal cord injury lesion at L4 complained of tingling, pins and needles, and burning in her legs. She scored her pain as 6 before adding baclofen 5% cream to her pain medication (pregabalin 450 mg, acetaminophen 3000 mg, and diclofenac 150 mg daily. One month later she experienced complete pain relief, though experienced increased difficulties in walking, leading to frequent falls. Her steadier walking without stumbling and falling was more important to her than pain reduction. Thus she decided to stop using baclofen. This unusual case report discusses two important issues that relate to pain medicine and rehabilitation in patients with painful spinal cord lesions: (1 the presence of wide areas of sensory loss “covered” by the presence of painful sensations and (2 pathological sensations that can be used and integrated in the body schema to create an improved spatiovisual orientation and thus mobility. Both these aspects have to be taken into account when treating pain and design rehabilitation programs.

  1. Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain.

    Science.gov (United States)

    Lefaucheur, Jean-Pascal; Drouot, Xavier; Cunin, Patrick; Bruckert, Rémy; Lepetit, Hélène; Créange, Alain; Wolkenstein, Pierre; Maison, Patrick; Keravel, Yves; Nguyen, Jean-Paul

    2009-06-01

    Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. Sixteen patients were included with pain origin as follows: trigeminal neuralgia (n = 4), brachial plexus lesion (n = 4), neurofibromatosis type-1 (n = 3), upper limb amputation (n = 2), herpes zoster ophthalmicus (n = 1), atypical orofacial pain secondary to dental extraction (n = 1) and traumatic nerve trunk transection in a lower limb (n = 1). A quadripolar lead was implanted, under radiological and electrophysiological guidance, for epidural cortical stimulation. A randomized crossover trial was performed between 1 and 3 months postoperative, during which the stimulator was alternatively switched 'on' and 'off' for 1 month, followed by an open phase during which the stimulator was switched 'on' in all patients. Clinical assessment was performed up to 1 year after implantation and was based on the following evaluations: visual analogue scale (VAS), brief pain inventory, McGill Pain questionnaire, sickness impact profile and medication quantification scale. The crossover trial included 13 patients and showed a reduction of the McGill Pain questionnaire-pain rating index (P = 0.0166, Wilcoxon test) and McGill Pain questionnaire sensory subscore (P = 0.01) when the stimulator was switched 'on' compared to the 'off-stimulation' condition. However, these differences did not persist after adjustment for multiple comparisons. In the 12 patients who completed the open study, the VAS and sickness impact profile scores varied significantly in the follow-up and were reduced at 9-12 months postoperative, compared to the preoperative baseline. At final examination, the mean rate of pain relief on VAS scores was 48% (individual results

  2. A preliminary report on stem cell therapy for neuropathic pain in humans

    Directory of Open Access Journals (Sweden)

    Vickers ER

    2014-05-01

    Full Text Available E Russell Vickers,1 Elisabeth Karsten,2 John Flood,3 Richard Lilischkis21Sydney Oral and Maxillofacial Surgery, NSW, Australia; 2Regeneus Ltd, Gordon, NSW, Australia; 3St Vincents Hospital, Sydney, NSW, AustraliaObjective: Mesenchymal stem cells (MSCs have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i injections of autologous MSCs can reduce human neuropathic pain and ii evaluate the safety of the procedure.Methods: Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i pain intensity measured by standard numerical rating scale from 0–10 and ii daily dosage requirements of antineuropathic pain medication.Results: Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites. Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58 and at 6 months had decreased to 4.3 (SD 3.28, P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student's t-test.Conclusion: This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain

  3. Intrathecal Ziconotide and Morphine for Pain Relief: A Case Series of Eight Patients with Refractory Cancer Pain, Including Five Cases of Neuropathic Pain

    OpenAIRE

    de la Calle Gil, Ana Bella; Peña Vergara, Isaac; Cormane Bornacelly, María Auxiliadora; Pajuelo Gallego, Antonio

    2015-01-01

    Introduction Studies have shown that, at low doses and with careful titration, combination therapy with intrathecal ziconotide and morphine results in rapid control of opioid-refractory cancer pain. However, there is a lack of published data regarding the efficacy and safety of intrathecal ziconotide specifically for the treatment of neuropathic cancer pain. Case series Case reports of ziconotide intrathecal infusion in eight patients (age 45–71 years; 75% male) with chronic, uncontrolled can...

  4. Neuropathic pain, back to the patient

    NARCIS (Netherlands)

    R. van Seventer (Robert)

    2011-01-01

    markdownabstract__Abstract__ Pain can be classified in several ways. The International Association for the Study of Pain (IASP) recommends describing pain according to five categories or axes, namely its anatomical location (neck, lower back, etc.), the body system involved (gastrointestinal, nervo

  5. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats

    OpenAIRE

    M’Dahoma, Saïd; Barthélemy, Sandrine; Tromilin, Claire; Jeanson, Tiffany; Viguier, Florent; Michot, Benoit; Pezet, Sophie; Hamon, Michel; Bourgoin, Sylvie

    2015-01-01

    International audience Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague–Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilatera...

  6. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain

    OpenAIRE

    Ragavendran, J. Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J.; Padi, Satyanarayana S.V.; Zhang, Ji; Coderre, Terence J.

    2013-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α2-adrenergic (α2A) receptor agonists or nitric oxide (NO) donors combi...

  7. Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain.

    Science.gov (United States)

    Cooper, Michael A; Kluding, Patricia M; Wright, Douglas E

    2016-01-01

    The utilization of physical activity as a therapeutic tool is rapidly growing in the medical community and the role exercise may offer in the alleviation of painful disease states is an emerging research area. The development of neuropathic pain is a complex mechanism, which clinicians and researchers are continually working to better understand. The limited therapies available for alleviation of these pain states are still focused on pain abatement and as opposed to treating underlying mechanisms. The continued research into exercise and pain may address these underlying mechanisms, but the mechanisms which exercise acts through are still poorly understood. The objective of this review is to provide an overview of how the peripheral nervous system responds to exercise, the relationship of inflammation and exercise, and experimental and clinical use of exercise to treat pain. Although pain is associated with many conditions, this review highlights pain associated with diabetes as well as experimental studies on nerve damages-associated pain. Because of the global effects of exercise across multiple organ systems, exercise intervention can address multiple problems across the entire nervous system through a single intervention. This is a double-edged sword however, as the global interactions of exercise also require in depth investigations to include and identify the many changes that can occur after physical activity. A continued investment into research is necessary to advance the adoption of physical activity as a beneficial remedy for neuropathic pain. The following highlights our current understanding of how exercise alters pain, the varied pain models used to explore exercise intervention, and the molecular pathways leading to the physiological and pathological changes following exercise intervention. PMID:27601974

  8. THE CLINICAL EFFECTS OF NERVE MANUAL PULSED RADIOFREQUENCY REGULATION TECHNOLOGY ON CHRONIC NEUROPATHIC PAIN%手动脉冲射频神经调控技术治疗慢性神经病理性痛

    Institute of Scientific and Technical Information of China (English)

    刘娜; 宫小文; 宋永光; 吴大胜

    2012-01-01

    Objective: To evaluation the clinical effects of nerve manual pulsed radiofrequency regulation technology on chronic neuropathic pain. Methods: 89 patients with chronic neuropathic pain were treated with neural manual pulsed radiofrequency regulation technology. The patients were followed up at 3 d, 3 m, 6 m and 1 y after treatment. The visual analogue scale (VAS) and clinical effects were evaluated. Results: The pre-operative VAS was 8.4 ± 1.6. The VAS at 3 d,l m, 3 m, 6 m and 1 y after operation were 2.9 ± 1.4, 2.1 ± 1.2, 1.6 ± 0.8, 1.2 ± 0.6 and 1.1 ± 0.6 respectively. Compared with pre-operation, the VAS after operation was decreased (P < 0.05). After 3 d treatment, the excellent cases were 77 (86.5%), the good cases were 12 (13.5%), and there was no invalid case. With the extension of time, the excellent cases were increasing. Conclusion: Nerve manual pulsed radiofrequency regulation technology for the treatment of chronic neuropathic pain disease has a good curative effect both in the short and long term. It is worthy to be promoted.%目的:评价手动脉冲射频神经调控技术对治疗慢性神经病理痛的治疗作用.方法:对89例慢性神经病理痛患者采用手动脉冲射频神经调控技术治疗.分别测定患者治疗前、治疗后3天、3个月、6个月、1年视觉模拟评分(visual analogue scale,VAS)并评估疗效.结果:术前VAS评分平均值为8.4±1.6.术后3天、1月、3月、6月、1年VAS评分分别为2.9±1.4、2.1±1.2、1.6±0.8、1.2±0.6、1.1±0.6.与术前相比,术后VAS评分显著降低(P<0.05).经手动脉冲射频神经调控治疗3d后,疗效为优77例(86.5%),疗效为良12例(13.5%),没有无效病例.且随着术后时间延长,疗效优的数量增加.结论:手动脉冲射频神经调控技术治疗慢性神经病理痛近期和远期疗效均好,值得推广.

  9. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor. PMID:27302204

  10. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury

    Science.gov (United States)

    Han, Zee‐A; Song, Dae Heon; Oh, Hyun‐Mi

    2016-01-01

    Objective To evaluate the analgesic effect of botulinum toxin type A (BTX‐A) on patients with spinal cord injury‐associated neuropathic pain. Methods The effect of BTX‐A on 40 patients with spinal cord injury‐associated neuropathic pain was investigated using a randomized, double‐blind, placebo‐controlled design. A 1‐time subcutaneous BTX‐A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0–100mm), the Korean version of the short‐form McGill Pain Questionnaire, and the World Health Organization WHOQOL‐BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection. Results At 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX‐A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX‐A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL‐BREF in the BTX‐A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection. Interpretation These results indicate that BTX‐A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. Ann Neurol 2016;79:569–578 PMID:26814620

  11. Tetrodotoxin-resistant sodium channels in neuropathic pain

    OpenAIRE

    Fjell Hjelmström, Jenny

    2000-01-01

    Injury to the peripheral nervous system can cause neuropathic pain. Abnormal sodium channel activity has been implicated as a source of ectopic firing and changes in nociceptive threshold following nerve injury. Primary sensory neurons exhibit at least two types of sodium currents: rapidly inactivating tetrodotoxin-sensitive (TTX-S) and slowly inactivating TTX-resistant (TTX-R) sodium currents. Two TTX-R sodium channels that are expressed in primary sensory neurons have been...

  12. Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain.

    Science.gov (United States)

    Sagheddu, Claudia; Aroni, Sonia; De Felice, Marta; Lecca, Salvatore; Luchicchi, Antonio; Melis, Miriam; Muntoni, Anna Lisa; Romano, Rosaria; Palazzo, Enza; Guida, Francesca; Maione, Sabatino; Pistis, Marco

    2015-10-01

    In humans, affective consequences of neuropathic pain, ranging from depression to anxiety and anhedonia, severely impair quality of life and are a major disease burden, often requiring specific medications. Depressive- and anxiety-like behaviors have also been observed in animal models of peripheral nerve injury. Dysfunctions in central nervous system monoamine transmission have been hypothesized to underlie depressive and anxiety disorders in neuropathic pain. To assess whether these neurons display early changes in their activity that in the long-term might lead to chronicization, maladaptive plasticity and affective consequences, we carried out in vivo extracellular single unit recordings from serotonin neurons in the dorsal raphe nucleus (DRN) and from dopamine neurons in ventral tegmental area (VTA) in the spared nerve injury (SNI) model of neuropathic pain in rats. Extracellular dopamine levels and the expression of dopamine D1, D2 receptors and tyrosine hydroxylase (TH) were measured in the nucleus accumbens. We report that, two weeks following peripheral nerve injury, discharge rate of serotonin DRN neurons and burst firing of VTA dopamine cells are enhanced, when compared with sham-operated animals. We also observed higher extracellular dopamine levels and reduced expression of D2, but not D1, receptors and TH in the nucleus accumbens. Our study confirms that peripheral neuropathy induces changes in the serotonin and dopamine systems that might be the early result of chronic maladaptation to persistent pain. The allostatic activation of these neural systems, which mirrors that already described as a consequence of stress, might lead to depression and anxiety previously observed in neuropathic animals but also an attempt to cope positively with the negative experience. PMID:26113399

  13. Nerve injury and neuropathic pain — A question of age

    Science.gov (United States)

    Fitzgerald, Maria; McKelvey, Rebecca

    2016-01-01

    The effects of peripheral nerve injury on somatosensory processing and pain are highly dependent upon the age at which the damage occurs. Adult nerve injury rapidly triggers neuropathic pain, but this is not so if the same nerve injury is performed in animals below postnatal day (P) 28, consistent with observations in paediatric patients. However, longitudinal studies show that pain hypersensitivity emerges later in life, when the animal reaches adolescence, an observation that could be of clinical importance. Here we discuss the evidence that the central consequences of nerve damage are critically determined by the status of neuroimmune regulation at different ages. In the first postnatal weeks, when spinal somatosensory circuits are undergoing synaptic reorganisation, the ‘default’ neuroimmune response is skewed in an anti-inflammatory direction, suppressing the excitation of dorsal horn neurons and preventing the onset of neuropathic pain. As animals grow up and the central nervous system matures, the neuroimmune profile shifts in a pro-inflammatory direction, unmasking a ‘latent’ pain response to an earlier nerve injury. The data predicts that nerve injury in infancy and childhood could go unnoticed at the time, but emerge as clinically ‘unexplained’ or ‘functional’ pain in adolescence. PMID:26220898

  14. Nerve injury and neuropathic pain - A question of age.

    Science.gov (United States)

    Fitzgerald, Maria; McKelvey, Rebecca

    2016-01-01

    The effects of peripheral nerve injury on somatosensory processing and pain are highly dependent upon the age at which the damage occurs. Adult nerve injury rapidly triggers neuropathic pain, but this is not so if the same nerve injury is performed in animals below postnatal day (P) 28, consistent with observations in paediatric patients. However, longitudinal studies show that pain hypersensitivity emerges later in life, when the animal reaches adolescence, an observation that could be of clinical importance. Here we discuss the evidence that the central consequences of nerve damage are critically determined by the status of neuroimmune regulation at different ages. In the first postnatal weeks, when spinal somatosensory circuits are undergoing synaptic reorganisation, the 'default' neuroimmune response is skewed in an anti-inflammatory direction, suppressing the excitation of dorsal horn neurons and preventing the onset of neuropathic pain. As animals grow up and the central nervous system matures, the neuroimmune profile shifts in a pro-inflammatory direction, unmasking a 'latent' pain response to an earlier nerve injury. The data predicts that nerve injury in infancy and childhood could go unnoticed at the time, but emerge as clinically 'unexplained' or 'functional' pain in adolescence.

  15. 慢病毒介导GDNF过表达对CCI大鼠神经病理性疼痛的影响%Effect of lentiviral vector-mediated GDNF up-regulation on neuropathic pain of chronic constriction injury rats

    Institute of Scientific and Technical Information of China (English)

    丁卓峰; 徐伟; 宋宗斌; 邹望远; 郭曲练

    2014-01-01

    Objective To investigate the effect of intrathecal injection of lentiviral vector-mediated up-regulation of glial cell line-derived neurotrophicfactor (GDNF) on neuropathic pain of chronic constriction injury (CCI) rats.Methods The CCI model was prepared by ligating the sciatic nerve of Sprague-Dawley (SD) rats.Seven days after CCI modeling,a single intrathecal injection of lentiviral vectors (LV)-GDNF was given.Before CCI and 3,5,7,14,and 21 days after CCI modeling,the mechanical pain threshold was tested in rats,and 21 days after surgery,Western blot was used to detect the expression of GDNF protein.Results On 21 days after CCI modeling,GDNF expression was reduced compared to sham group.After intrathecal injection of LV-GDNF,GDNF expression was up-regulated in the spinal cord,and CCI-induced mechanical hyperalgesia in rats was alleviated.Conclusions Intrathecal injection LV-GDNF can up-regulate the expression of GDNF and alleviate neuropathic pain in CCI rats.%目的 观察鞘内注射过表达胶质细胞源性神经生长因子(GDNF)慢病毒载体对慢性缩窄性神经损伤(CCI)大鼠神经病理性疼痛的影响.方法 采用结扎大鼠坐骨神经制备CCI模型.CCI造模成功后第7天鞘内注射GDNF过表达慢病毒载体.CCI造模前及造模后第3、5、7、14、21天测定大鼠机械痛阈,并于术后第21天采用Western免疫印迹法测定脊髓GDNF表达.结果 Western免疫印迹显示CCI组GDNF表达较假手术组减少(P<0.05);鞘内注射GDNF过表达慢病毒载体后,脊髓GDNF表达上调,且CCI大鼠机械痛敏显著降低(P<0.05).结论 上调脊髓GDNF表达可减轻CCI大鼠神经病理性疼痛.

  16. H2 Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain.

    Science.gov (United States)

    Chen, Yajun; Chen, Hongguang; Xie, Keliang; Liu, Lingling; Li, Yuan; Yu, Yonghao; Wang, Guolin

    2015-10-01

    Neuropathic pain (NP) is characterized by persistent pain, tactile allodynia, or hyperalgesia. Peripheral nerve injury contributes to rapid progress of inflammatory response and simultaneously generates neuropathic pain. Hydrogen (H2) has anti-inflammation, anti-apoptosis, and anti-oxidative stress effects. Therefore, we hypothesized that H2 treatment could alleviate allodynic and hyperalgesic behaviors and the release of inflammatory factors in rats with neuropathic pain. Peripheral neuropathic pain was established by chronic constriction injury of sciatic nerve in rats. H2 was given twice through intraperitoneal injection at a daily dose of 10 mL/kg during days 1-7 after the operation. Hyperalgesia and allodynia were tested, pro-inflammatory factors of dorsal root ganglia (DRG) and the spinal cord were measured by enzyme-linked immunosorbent assay (ELISA) during days 1-14 after the operation, and heme oxygenase (HO)-1 messenger RNA (mRNA) and protein expression and activities were measured at day 14 after sciatic nerve injury in rats. After Sn (IV) protoporphyrin IX dihydrochloride (SnPP)-IX, hemin, and carbon monoxide-releasing molecule (CORM)-2 had been given for chronic constriction injury (CCI) in rats, the above indicators were assessed. We found that H2 clearly inhibited hyperalgesia and allodynia in neuropathic pain and also attenuated the pro-inflammatory cytokines TNF-α, IL-1β, and high-mobility group box (HMGB) 1. H2 improved HO-1 mRNA and protein expression and activities in the process of pain. SnPP-IX reversed the inhibitory effect of H2 on hyperalgesia and allodynia and on pro-inflammatory cytokines in DRG and the spinal cord. The antinociceptive and anti-inflammatory effects of H2 were involved in the activation of HO-1/CO signaling during neuropathic pain in rats. PMID:25820467

  17. DDD-028: a potent potential non-opioid, non-cannabinoid analgesic for neuropathic and inflammatory pain.

    Science.gov (United States)

    Rajagopalan, Parthasarathi; Tracey, Heather; Chen, Zhoumou; Bandyopadhyaya, Acintya; Veeraraghavan, Sridhar; Rajagopalan, Desikan R; Salvemini, Daniela; McPhee, Ian; Viswanadha, Srikant; Rajagopalan, Raghavan

    2014-07-15

    DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities.

  18. Are Spinal GABAergic Elements Related to the Manifestation of Neuropathic Pain in Rat?

    OpenAIRE

    Lee, Jaehee; Back, Seung Keun; Lim, Eun Jeong; Cho, Gyu Chong; Kim, Myung Ah; Kim, Hee Jin; Lee, Min Hee; Na, Heung Sik

    2010-01-01

    Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these ai...

  19. Gabapentin Treatment for Neuropathic Pain in a Child with Sciatic Nerve Injury

    Science.gov (United States)

    Akkurt, Halil Ekrem; Gümüş, Haluk; Göksu, Hamit; Odabaşı, Ömer Faruk; Yılmaz, Halim

    2015-01-01

    There are a restricted number of studies about usage of gabapentin for neuropathic pain treatment of pediatric patients. We shared a 12-year-old male case with severe neuropathic pain that hindered the rehabilitation programme for the loss of muscle power and movement limitation. Neuropathic pain developed after peripheral sciatic damage due to firearm traumatisation did not respond to other medical treatments but healed nearly completely after gabapentin usage. PMID:26346828

  20. Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model

    OpenAIRE

    Enji Zhang; Min-Hee Yi; Nara Shin; Hyunjung Baek; Sena Kim; Eunjee Kim; Kisang Kwon; Sunyeul Lee; Hyun-Woo Kim; Yong Chul Bae; Yonghyun Kim; O.-Yu Kwon; Won Hyung Lee; Dong Woon Kim

    2015-01-01

    Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuro...

  1. Antinociceptive effect of ambroxol in rats with neuropathic spinal cord injury pain

    Science.gov (United States)

    Hama, Aldric T.; Plum, Ann Woodhouse; Sagen, Jacqueline

    2010-01-01

    Symptoms of neuropathic spinal cord injury (SCI) pain include evoked cutaneous hypersensitivity and spontaneous pain, which can be present below the level of the injury. Adverse side-effects obtained with currently available analgesics complicate effective pain management in SCI patients. Voltage-gated Na+ channels expressed in primary afferent nociceptors have been identified to mediate persistent hyperexcitability in dorsal root ganglia (DRG) neurons, which in part underlies the symptoms of nerve injury-induced pain. Ambroxol has previously demonstrated antinociceptive effects in rat chronic pain models and has also shown to potently block Na+ channel current in DRG neurons. Ambroxol was tested in rats that underwent a mid-thoracic spinal cord compression injury. Injured rats demonstrated robust hind paw (below-level) heat and mechanical hypersensitivity. Orally administered ambroxol significantly attenuated below-level hypersensitivity at doses that did not affect performance on the rotarod test. Intrathecal injection of ambroxol did not ameliorate below-level hypersensitivity. The current data suggest that ambroxol could be effective for clinical neuropathic SCI pain. Furthermore, the data suggests that peripherally expressed Na+ channels could lend themselves as targets for the development of pharmacotherapies for SCI pain. PMID:20732348

  2. Managing your chronic pain

    Science.gov (United States)

    ... your chronic back pain To use the sharing features on this page, please enable JavaScript. Managing chronic pain means finding ways to make your back pain tolerable so you can live your life. You may not be able to ...

  3. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... chronic pain there may be no apparent physical injury or illness to explain it. The physician and ... expected period of healing for an illness or injury. You can experience pain even if you are ...

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

    Directory of Open Access Journals (Sweden)

    Hannah L Pellkofer

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

  5. Medication Treatment Efficacy and Chronic Orofacial Pain.

    Science.gov (United States)

    Clark, Glenn T; Padilla, Mariela; Dionne, Raymond

    2016-08-01

    Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (β-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful. PMID:27475515

  6. Evaluation of milnacipran, in comparison with amitriptyline, on cold and mechanical allodynia in a rat model of neuropathic pain.

    Science.gov (United States)

    Berrocoso, Esther; Mico, Juan-Antonio; Vitton, Olivier; Ladure, Philippe; Newman-Tancredi, Adrian; Depoortère, Ronan; Bardin, Laurent

    2011-03-25

    Milnacipran, a serotonin/norepinephrine reuptake inhibitor (SNRI), has shown efficacy against several chronic pain conditions, including fibromyalgia. Here, we evaluated, in rats, its anti-allodynic effects following acute or sub-chronic treatment in a model of neuropathic pain (chronic constriction injury, CCI, of the sciatic nerve). Amitriptyline, a tricyclic antidepressant active pre-clinically and clinically against neuropathic pains, was added as a comparison compound. Upon acute i.p. administration, milnacipran was potently efficacious in the CCI model. It significantly reduced thermal allodynia in the cold (4°C) plate test (MED=2.5mg/kg), and attenuated mechanical allodynia in the von Frey filaments test (MED=10mg/kg). Given sub-chronically (7day, b.i.d.), milnacipran was effective at 10mg/kgi.p. in both tests. Acute amitriptyline (10mg/kgi.p.) was efficacious against mechanical, but less so against cold allodynia; under sub-chronic conditions, it was only active against mechanical allodynia. These data show that milnacipran is as efficacious as the reference compound amitriptyline in a pre-clinical model of injury-induced neuropathy, and demonstrate for the first time that it is active acutely and sub-chronically against cold allodynia. They also suggest that milnacipran has the potential to alleviate allodynia associated with nerve compression-induced neuropathic pain in the clinic (for example following discal hernia, avulsion or cancer-induced tissue damage). PMID:21277295

  7. Genitofemoral neuralgia: adding to the burden of chronic vulvar pain

    Directory of Open Access Journals (Sweden)

    Verstraelen H

    2015-11-01

    Full Text Available Hans Verstraelen,1 Eline De Zutter,1 Martine De Muynck2 1Department of Obstetrics and Gynaecology, Vulvovaginal Disease Clinic, Ghent University Hospital, Ghent, Belgium; 2Department of Physical Medicine and Rehabilitation, Ghent University Hospital, Ghent, Belgium Abstract: The vulva is a particularly common locus of chronic pain with neuropathic characteristics that occurs in women of any age, though most women with neuropathic type chronic vulvar pain will remain undiagnosed even following multiple physician visits. Here, we report on an exemplary case of a middle-aged woman who was referred to the Vulvovaginal Disease Clinic with debilitating vulvar burning and itching over the right labium majus that had been persisting for 2 years and was considered intractable. Careful history taking and clinical examination, followed by electrophysiological assessment through somatosensory evoked potentials was consistent with genitofemoral neuralgia, for which no obvious cause could be identified. Adequate pain relief was obtained with a serotonin–noradrenaline reuptake inhibitor and topical gabapentin cream. We briefly discuss the epidemiology, diagnosis, and treatment of genitofemoral neuralgia and provide a series of clues to guide clinicians in obtaining a presumptive diagnosis of specific neuropathic pain syndromes that may underlie chronic vulvar pain. We further aim to draw attention to the tremendous burden of chronic, unrecognized vulvar pain. Keywords: vulvar pain, genitofemoral nerve, neuropathic pain, vulvodynia, vulvar disease

  8. A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development

    OpenAIRE

    Wilkes D; Li G; Angeles CF; Patterson JT; Huang LY

    2012-01-01

    Denise Wilkes,1 Guangwen Li,2 Carmina F Angeles,3 Joel T Patterson,4 Li-Yen Mae Huang21Department of Anesthesiology, 2Department of Neuroscience and Cell Biology, 3Department of Neurosurgery University of Texas Medical Branch, Galveston, TX, USA; 4Neurospine Institute, Eugene, OR, USABackground: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large ...

  9. Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sagen J

    2016-06-01

    tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus.Conclusion: These findings showed that mepivacaine, rather than lidocaine, consistently attenuated two distinct symptoms of neuropathic pain and suggest that topical formulations of this local anesthetic could have utility in the alleviation of clinical HIV neuropathic pain. Keywords: chronic pain, acute pain, analgesia, AIDs-related pain, distal sensory neuropathy, local anesthetics

  10. Tapentadol extended release in the management of peripheral diabetic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2015-01-01

    Full Text Available Nalini Vadivelu,1 Alice Kai,2 Benjamin Maslin,1 Gopal Kodumudi,3 Aron Legler,1 Jack M Berger4 1Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 2Stony Brook University School of Medicine, Stony Brook, NY, USA; 3Department of Structural and Cellular Biology, Tulane University, New Orleans, LA, USA; 4Department of Anesthesiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Tapentadol, a µ-opioid agonist and norepinephrine reuptake inhibitor, has been found to be an effective medication for a wide variety of chronic pain conditions, including back pain, cancer-related pain, and arthritic pain. It has also been found to have fewer gastrointestinal side effects than more traditional opioid-based therapies. More recently, tapentadol extended release has been demonstrated to be effective in the management of painful diabetic neuropathy, an often debilitating condition affecting approximately one-third of all patients with diabetes. This review highlights the most up-to-date basic and clinical studies by focusing on the mechanisms of action of tapentadol and its clinical efficacy, especially with regard to painful diabetic neuropathy. Keywords: chronic pain, neuropathic pain, pharmacology, analgesia, pain management

  11. Interleukin-17A Acts to Maintain Neuropathic Pain Through Activation of CaMKII/CREB Signaling in Spinal Neurons.

    Science.gov (United States)

    Yao, Cheng-Ye; Weng, Ze-Lin; Zhang, Jian-Cheng; Feng, Tao; Lin, Yun; Yao, Shanglong

    2016-08-01

    Immunity and neuroinflammation play major roles in neuropathic pain. Spinal interleukin (IL)-17A, as a mediator connecting innate and adaptive immunity, has been shown to be an important cytokine in neuroinflammation and acute neuropathic pain. However, the effects and underlying mechanisms of spinal IL-17A in the maintenance of neuropathic pain remain unknown. This study was designed to investigate whether spinal IL-17A acted to maintain neuropathic pain and to elucidate the underlying mechanisms in IL-17A knockout or wild-type (WT) mice following L4 spinal nerve ligation (L4 SNL). WT mice were treated with anti-IL-17A neutralized monoclonal antibody (mAb) or recombinant IL-17A (rIL-17A). We showed that IL-17A levels were significantly increased 1, 3, 7, and 14 days after SNL in spinal cord. Double immunofluorescence staining showed that astrocytes were the major cellular source of spinal IL-17A. IL-17A knockout or anti-IL-17A mAb treatment significantly ameliorated hyperalgesia 7 days after SNL, which was associated with a significant reduction of p-CaMKII and p-CREB levels in spinal cord, whereas rIL-17A treatment conferred the opposite effects. Furthermore, we showed that blocking CaMKII with KN93 significantly reduced SNL- or rIL-17A-induced hyperalgesia and p-CREB expression. Our in vitro data showed that KN93 also significantly inhibited rIL-17A-induced CREB activation in primary cultured spinal neurons. Taken together, our study indicates that astrocytic IL-17A plays important roles in the maintenance of neuropathic pain through CaMKII/CREB signaling pathway in spinal cord, and thus targeting IL-17A may offer an attractive strategy for the treatment of chronic persistent neuropathic pain. PMID:26166359

  12. Chronic Pain: Where the Body Meets the Brain.

    Science.gov (United States)

    Crofford, Leslie J

    2015-01-01

    Chronic musculoskeletal pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Central pain amplification is perceived pain that cannot be fully explained on the basis of somatic or neuropathic processes and is due to physiologic alterations in pain transmission or descending pain modulatory pathways. In any individual, central pain amplification may complicate nociceptive or neuropathic pain. Furthermore, patients with somatic symptom disorders may have alterations in their psychological or behavioral responses to pain that contribute significantly to the clinical presentation. Genetic, physiologic, and psychological factors associated with central pain amplification are beginning to be understood. One important contributor to chronic pain is perceived stress and stress response systems. We and others have shown a complex relationship between the physiologic stress response and chronic pain symptoms. Unfortunately, treatments for chronic pain are woefully inadequate and often worsen clinical outcomes. Developing new treatment strategies for patients with chronic pain is of utmost urgency. This essay provides a framework for thinking about chronic pain and developing new treatment approaches. PMID:26330672

  13. Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Katarzyna Popiolek-Barczyk

    2014-01-01

    Full Text Available Nociceptin/orphanin FQ (N/OFQ antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP, was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p., a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.. Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain.

  14. Minocycline Enhances the Effectiveness of Nociceptin/Orphanin FQ during Neuropathic Pain

    Science.gov (United States)

    Popiolek-Barczyk, Katarzyna; Rojewska, Ewelina; Jurga, Agnieszka M.; Makuch, Wioletta; Zador, Ferenz; Piotrowska, Anna; Przewlocka, Barbara

    2014-01-01

    Nociceptin/orphanin FQ (N/OFQ) antinociception, which is mediated selectively by the N/OFQ peptide receptor (NOP), was demonstrated in pain models. In this study, we determine the role of activated microglia on the analgesic effects of N/OFQ in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. Repeated 7-day administration of minocycline (30 mg/kg i.p.), a drug that affects microglial activation, significantly reduced pain in CCI-exposed rats and it potentiates the analgesic effects of administered N/OFQ (2.5–5 μg i.t.). Minocycline also downregulates the nerve injury-induced upregulation of NOP protein in the dorsal lumbar spinal cord. Our in vitro study showed that minocycline reduced NOP mRNA, but not protein, level in rat primary microglial cell cultures. In [35S]GTPγS binding assays we have shown that minocycline increases the spinal N/OFQ-stimulated NOP signaling. We suggest that the modulation of the N/OFQ system by minocycline is due to the potentiation of its neuronal antinociceptive activity and weakening of the microglial cell activation. This effect is beneficial for pain relief, and these results suggest new targets for the development of drugs that are effective against neuropathic pain. PMID:25276817

  15. Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

    OpenAIRE

    Bravo, Lidia; Alba-Delgado, Cristina; Torres-Sanchez, Sonia; Micó, Juan Antonio; Neto, Fani L; Berrocoso, Esther

    2013-01-01

    Stressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain...

  16. Ethanolic extract of Aloe vera ameliorates sciatic nerve ligation induced neuropathic pain

    Directory of Open Access Journals (Sweden)

    Swetha Kanyadhara

    2014-01-01

    Conclusion: The results of the present study validate the use of EEAV to treat neuropathic pain. This effect may be attributed to the decreased migration of neutrophils and due to the anti-oxidant properties of A. vera. Further studies to confirm the mechanism of action will help develop suitable A. vera formulations for neuropathic pain therapy .

  17. Agmatine reversed mechanical allodynia in a rat model of neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    YANGHong-Ju; ZhAONan; GONGZheng-Hua; YUANWei-Xiou; LIYunFeng; LI-Jin; LUOZhi-Pu

    2004-01-01

    AIM: Agmatine is an endogenous neuromodulator present in the brain and spinal cord, agmatine has both NMDA receptor antagonist and NOS inhibitor activities, which may participate the pathological process in the neuropathic pain. The effect of agmatine on the mechanical allodynia in a rat model of the neuropathic pain was investigated in this experiment.

  18. The effect of Normast (PEA) on neuropathic pain in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede;

    2015-01-01

    Introduction: Neuropathic pain and spasticity after spinal cord injury (SCI) represent still a significant, unresolved problem causing suffering and re¬duced quality of life in patients with SCI. Treatment of neuropathic pain is a complex and difficult task, and many patients have incom¬plete rel...

  19. An evidence-based algorithm for the treatment of neuropathic pain

    DEFF Research Database (Denmark)

    Finnerup, Nanna B; Otto, Marit; Jensen, Troels S;

    2007-01-01

    OBJECTIVE: The purpose of this article is to discuss an evidence-based algorithm that can be implemented by the primary care physician in his/her daily clinical practice for the treatment of patients with neuropathic pain conditions. METHOD: A treatment algorithm for neuropathic pain was formulat...

  20. Alpha lipoic acid : a new treatment for neuropathic pain in patients with diabetes?

    NARCIS (Netherlands)

    Mijnhout, G. S.; Alkhalaf, A.; Kleefstra, N.; Bibo, H. J. G.

    2010-01-01

    Background: Neuropathic pain is difficult to treat. We identified those studies in the literature in which the effectiveness of alpha lipoic acid as a treatment for neuropathic pain was evaluated. Methods: Systematic literature review. The databases MEDLINE and EMBASE were searched using the keyword

  1. Use of 5% lidocaine medicated plaster to treat localized neuropathic pain secondary to traumatic injury of peripheral nerves

    Directory of Open Access Journals (Sweden)

    Correa-Illanes G

    2012-07-01

    Full Text Available Gerardo Correa-Illanes,1 Ricardo Roa,2 José Luis Piñeros,2 Wilfredo Calderón31Rehabilitation Department, 2Burns and Plastic Surgery Department, Hospital del Trabajador, 3Plastic Surgery Department, Hospital del Salvador, Santiago, ChileObjective: The efficacy of 5% lidocaine medicated plaster (LMP has previously been demonstrated in post-traumatic localized neuropathic pain. This study evaluated the use of LMP in localized neuropathic pain secondary to traumatic peripheral nerve injury.Patients and methods: This prospective observational study enrolled patients with traumatic injuries to peripheral nerves that were accompanied by localized neuropathic pain of more than 3 months duration. Demographic variables, pain intensity (measured using the numeric rating scale; NRS, answers to the Douleur Neuropathique 4 (DN4 questionnaire, and the size of the painful area were recorded.Results: Nineteen patients were included, aged (mean ± standard deviation 41.4 ± 15.7 years. Nerve injuries affected the upper (eight patients or lower (11 patients limbs. The mean duration of pain before starting treatment with LMP was 22.6 ± 43.5 months (median 8 months. Mean baseline values included: NRS 6.7 ± 1.6, painful area 17.8 ± 10.4 cm2 (median 18 cm2, and DN4 score 6.7 ± 1.4. The mean duration of treatment with LMP was 19.5 ± 10.0 weeks (median 17.4 weeks. Mean values after treatment were: NRS 2.8 ± 1.5 (≥3 point reduction in 79% of patients, ≥50% reduction in 57.9% of patients and painful area 2.1 ± 2.3 cm2 (median 1 cm2, ≥50% reduction in 94.7% of patients. Functional improvement after treatment was observed in 14/19 patients (73.7%.Conclusion: LMP effectively treated traumatic injuries of peripheral nerves which presented with chronic localized neuropathic pain, reducing both pain intensity and the size of the painful area.Keywords: chronic post-surgical pain, chronic post-traumatic pain, 5% lidocaine medicated plaster, neuropathic pain

  2. The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Ombretta Caspani

    Full Text Available Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.

  3. Neuropathic pruritus.

    Science.gov (United States)

    Misery, Laurent; Brenaut, Emilie; Le Garrec, Raphaële; Abasq, Claire; Genestet, Steeve; Marcorelles, Pascale; Zagnoli, Fabien

    2014-07-01

    Pruritus, also known as itch, is a very common, unpleasant sensation that elicits an urge to scratch. Its origin is not always in the skin, and neuropathic itch that is caused by neuronal or glial damage is common, but poorly understood by both dermatologists and neurologists. Although pruritus has not been considered as serious a symptom as pain, it is difficult to treat and--if chronic--can severely impair quality of life. Neuropathic itch is often associated with other clinical symptoms, most commonly neuropathic pain, and hypersensitization to stimuli is present in both pruritus and pain of neuropathic origin. The shared aetiology can aid in finding suitable treatment for itch in some cases, but more detailed knowledge of the mechanisms of itch, along with standardized, well-controlled trials, is needed. Pruritus research is an emerging but currently very active field, and our understanding of this sensation is rapidly increasing. Here, we review new discoveries regarding the role of the nervous system and the contribution of different pathways in pruritus, discuss the different aetiologies of neuropathic itch, and outline currently available and potential strategies for managing neuropathic pruritus.

  4. D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.

    Science.gov (United States)

    Palazzo, Enza; Luongo, Livio; Guida, Francesca; Marabese, Ida; Romano, Rosaria; Iannotta, Monica; Rossi, Francesca; D'Aniello, Antimo; Stella, Luigi; Marmo, Federica; Usiello, Alessandro; de Bartolomeis, Andrea; Maione, Sabatino; de Novellis, Vito

    2016-07-01

    D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice. PMID:27115160

  5. Lysophosphatidic acid (LPA) signaling in neuropathic pain development and Schwann cell biology

    OpenAIRE

    Lin, Mu-En

    2012-01-01

    Neuropathic pain is a chonic pain state caused by lesions or diseases in the nervous system. Unlike acute pain, neuropathic pain persists without obvious injury or stimuli and can severely interfere with normal daily life for those who suffer from it. Despite numerous efforts on studying its mechanism and possible treatments, there is no effective treatment currently available to remove or alleviate this symptom. This dissertation aims to provide further understanding into the relationship be...

  6. Macrophage Migration Inhibitory Factor (MIF) is Essential for Inflammatory and Neuropathic Pain and Enhances Pain in Response to Stress

    OpenAIRE

    Alexander, Jessica K.; Cox, Gina M; Tian, Jin-Bin; Zha, Alicia M.; Wei, Ping; KIGERL, KRISTINA A.; Reddy, Mahesh K.; Dagia, Nilesh M.; Sielecki, Theis; Zhu, Michael X.; Satoskar, Abhay R.; Dana M. McTigue; Whitacre, Caroline C.; Popovich, Phillip G.

    2012-01-01

    Stress and glucocorticoids exacerbate pain via undefined mechanisms. Macrophage migration inhibitory factor (MIF) is a constitutively expressed protein that is secreted to maintain immune function when glucocorticoids are elevated by trauma or stress. Here we show that MIF is essential for the development of neuropathic and inflammatory pain, and for stress-induced enhancement of neuropathic pain. Mif null mutant mice fail to develop pain-like behaviors in response to inflammatory stimuli or ...

  7. Mechanism for chronic pain generation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Neuropathic pain and the other abnormalities of sensation induced by axon injury or by peripheral nerve inflammation should result from functional compensations of the injured neurons during their regeneration. Ectopic distribution of proteins related to Na+, K+ and Ca2+ channels as well as of receptors on both membranes of injured axon and its cell body becomes a main pacemaker from which spontaneous ectopic afferent of primary sensatory neurons and crosstalk between neurons occur. Abnormal ectopic afferent activities lead to disorders of the sensation, such as hyperalgesia, allodynia, spontaneous pain and paraesthesia. Administration of some ion channel agents and/or α2-adrenergic blockers has shown efficiency in preventing neuropathic pain development and in relieving neuropathic pain.

  8. Combination of pregabalin and palmitoylethanolamide (PEA for neuropathic pain treatment

    Directory of Open Access Journals (Sweden)

    Paolo Desio

    2010-12-01

    Full Text Available 30 patients ranging between 32 to 78 years, suffering from neuropathicpain, were treated with pregabalin and palmitoylethanolamide for 45 days. All patients have completed the study and no side effect was reported; in all patients it has been observed a significant reduction of pain intensity that was associated to a better quality of the sleep. The improvement of the clinical symptomatology was associated to a recovery of quality of sleep and to a good subjective evaluation of the effectiveness of the therapy. In conclusion, the efficacy of a new multitherapeutic approach for neuropathic pain, based on pregabalin + palmitoylethanolamide has been proved; the therapy showed to be safe and allows patients to have a better quality of life.

  9. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain

    Science.gov (United States)

    Kostich, Walter; Hamman, Brian D.; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V.; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K.; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M.; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O’Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H.; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E.; Lentz, Kimberley A.; Santone, Kenneth S.; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K.; Nara, Susheel J.; Dzierba, Carolyn; Bronson, Joanne; Macor, John E.; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M.

    2016-01-01

    To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor–induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2

  10. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.

    Science.gov (United States)

    Kostich, Walter; Hamman, Brian D; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O'Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E; Lentz, Kimberley A; Santone, Kenneth S; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K; Nara, Susheel J; Dzierba, Carolyn; Bronson, Joanne; Macor, John E; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M; Zambrowicz, Brian; Albright, Charles F

    2016-09-01

    To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor-induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2

  11. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.

    Science.gov (United States)

    Kostich, Walter; Hamman, Brian D; Li, Yu-Wen; Naidu, Sreenivasulu; Dandapani, Kumaran; Feng, Jianlin; Easton, Amy; Bourin, Clotilde; Baker, Kevin; Allen, Jason; Savelieva, Katerina; Louis, Justin V; Dokania, Manoj; Elavazhagan, Saravanan; Vattikundala, Pradeep; Sharma, Vivek; Das, Manish Lal; Shankar, Ganesh; Kumar, Anoop; Holenarsipur, Vinay K; Gulianello, Michael; Molski, Ted; Brown, Jeffrey M; Lewis, Martin; Huang, Yanling; Lu, Yifeng; Pieschl, Rick; O'Malley, Kevin; Lippy, Jonathan; Nouraldeen, Amr; Lanthorn, Thomas H; Ye, Guilan; Wilson, Alan; Balakrishnan, Anand; Denton, Rex; Grace, James E; Lentz, Kimberley A; Santone, Kenneth S; Bi, Yingzhi; Main, Alan; Swaffield, Jon; Carson, Ken; Mandlekar, Sandhya; Vikramadithyan, Reeba K; Nara, Susheel J; Dzierba, Carolyn; Bronson, Joanne; Macor, John E; Zaczek, Robert; Westphal, Ryan; Kiss, Laszlo; Bristow, Linda; Conway, Charles M; Zambrowicz, Brian; Albright, Charles F

    2016-09-01

    To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor-induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2

  12. Role of COX-1 in the process of neuropathic pain and its mechanism Zhi-hong LU, Qi - bing MEI

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    AIM In neuropathic pain the peripheral or central nervous systems are malfunctioning and become the cause of the pain. Unlike other pain styles, most neuropathic pain responds poorly to opioid analgesics. The mainstay of treatment is predominantly the tricyclic antidepressants, the anticonvulsants and the systemic local anesthetics of which the long- term use could lead to great side effects. Recently, proin-flammatory cytokines, such as IL-6, TNF-α, etc, have been proved to be involved in the process of neuropathic pain, indicating the cross - talking between neuropathic pain and inflammation. As an important member in inflammatory process, COX is expected to play a part in the process of neuropathic pain.In this study, we observed the change of COX-1 after neuropathic pain and further investigated thechange it caused in the brain. METHODS Spared nerve injury (SNI) is used to induce neuropathic painin mice.

  13. Pain treatment with ziconotide and baclofen in a case of spasticity associated with neuropathic pain

    OpenAIRE

    Danilo G. Quarta; Allegra Cionini Ciardi; Daniela Clerici; Patrizia Spina; Luigi Parigi

    2009-01-01

    This study presents the clinical case of a patient with paraparesis, subjected for a long period of time to treatment with intrathecal baclofen and morphine to control spasticity and neuropathic pain, resulting from spinal cord injury due to road trauma. After several years of treatment the pain was not controlled with high doses of intrathecal morphine combined with transmucosal fentanyl that were given when needed. It was therefore decided to switch to intrathecal ziconotide. Starting with ...

  14. Neuroimaging revolutionizes therapeutic approaches to chronic pain

    Directory of Open Access Journals (Sweden)

    Borsook David

    2007-09-01

    Full Text Available Abstract An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1 Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2 Functional Imaging (fMRI that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI; (3 Chemical Imaging (Magnetic Resonance Spectroscopy or MRS has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain – it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Effect of percutaneous radiofrequency thermocoagulation on different neuropathic pains

    Institute of Scientific and Technical Information of China (English)

    Youcai Shi; Xiaoxia Hu

    2006-01-01

    BACKGROUND: The clinical treatment of neuropathic pain is very troublesome ,and the physical method of radiofrequency thermocoagulation is a good choice for its treatment.OBJECTIVE: To observe the curative effact of percutaneous radiofrequency thermocoagulation on neuropathic neuralgia.DESIGN:A case follow-up analysis.SETTING: Minimally Invasive Surgery Room,Department of Neurosurgery,Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 131 patients were selected from the Department of Neurosurgery,Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA from December 2000 to June 2006,including 73 males and 58 females,aging 37-72 years old,AND the disease course was 2-15 years.①Drug treatment failed to alleviate the pain or induced obvious side the pain or induced obvious side effects; ②With the same pathological changes as pain and effective in the nerve block test; Had signed the informed consents before treatment.Distribution of the neuropathic pain:①Trigeminal neuralgia,which were lighting attack,located at V2 in 28 cases,V3 in 46 cases,V1+V2 in 3 cases,V2+V3 in 28 cases,and V1+V2+V3 in 1 cases;②Migraine located at(except the frontal branch of trigeminal nerve)greater and lesser occipital nerves in 6 cases,auriculotemporal nerve in 3 cases,temporal and zygomatic nerves in 3 cases;③Unilateral neuralgia of C2 and C3 following herpes zoster in 1 case,and chest intercostals neuralgia in 2 cases;④Lasting burning pain in the operative area after thoracotomy was in 1 case of lung cancer.METHODS: ①All the enrolled patients were treated with percutaneous puncture at trigeminal ganglion or peripheral nerve,then nerve block was performed firstly for anesthesia,and the pain disappeared immediately at this moment,there was hypoesthesia or numbness in the area of innervation,which manifested the puncture apposition was correct.then electrostimulation of 50 Hz with the current of 0.1-0.5 V was given for

  17. Phase-specific plasticity of synaptic structures in the somatosensory cortex of living mice during neuropathic pain

    Directory of Open Access Journals (Sweden)

    Kim Sun

    2011-11-01

    Full Text Available Abstract Background Postsynaptic dendritic spines in the cortex are highly dynamic, showing rapid morphological changes including elongation/retraction and formation/elimination in response to altered sensory input or neuronal activity, which achieves experience/activity-dependent cortical circuit rewiring. Our previous long-term in vivo two-photon imaging study revealed that spine turnover in the mouse primary somatosensory (S1 cortex markedly increased in an early development phase of neuropathic pain, but was restored in a late maintenance phase of neuropathic pain. However, it remains unknown how spine morphology is altered preceding turnover change and whether gain and loss of presynaptic boutons are changed during neuropathic pain. Findings Here we used short-term (2-hour and long-term (2-week time-lapse in vivo two-photon imaging of individual spines and boutons in the S1 cortical layer 1 of the transgenic mice expressing GFP in pyramidal neurons following partial sciatic nerve ligation (PSL. We found in the short-term imaging that spine motility (Δ length per 30 min significantly increased in the development phase of neuropathic pain, but returned to the baseline in the maintenance phase. Moreover, the proportion of immature (thin and mature (mushroom spines increased and decreased, respectively, only in the development phase. Long-term imaging data showed that formation and elimination of boutons moderately increased and decreased, respectively, during the first 3 days following PSL and was subsequently restored. Conclusions Our results indicate that the S1 synaptic structures are rapidly destabilized and rearranged following PSL and subsequently stabilized in the maintenance phase of neuropathic pain, suggesting a novel therapeutic target in intractable chronic pain.

  18. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... after a period of time the spinal cord has changed, after a period of time there are ... absence of an apparent cause. But chronic pain has a physiological or neurological basis even when we ...

  19. Neuropathic pain. Redefinition and a grading system for clinical and research purposes

    DEFF Research Database (Denmark)

    Treede, R.-D.; Jensen, Troels Staehelin; Campbell, J.N.;

    2008-01-01

    potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as "pain...... initiated or caused by a primary lesion or dysfunction in the nervous system." While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate...... affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific...

  20. Economic burden of back and neck pain: effect of a neuropathic component.

    Science.gov (United States)

    Kleinman, Nathan; Patel, Aarti A; Benson, Carmela; Macario, Alex; Kim, Myoung; Biondi, David M

    2014-08-01

    This was a retrospective database analysis (2001-2009) of employees' medical, prescription drug, and absence costs and days from sick leave, short- and long-term disability, and workers' compensation. Employees with an ICD-9 diagnostic code for back or neck pain and an ICD-9 for a back- or neck-related neuropathic condition (eg, myelopathy, compression of the spinal cord, neuritis, radiculitis) or radiculopathy were considered to have nociceptive back or neck pain with a neuropathic component. Employees with an ICD-9 for back pain or neck pain and no ICD-9 for a back- or neck-related neuropathic condition or radiculopathy were defined to have nociceptive back or neck pain. Patients with nociceptive back or neck pain with a neuropathic component were classified as having or not having prior nociceptive pain. Annual costs (medical and prescription drug costs and absence costs) and days from sick leave, short- and long-term disability, and workers' compensation were evaluated. Mean annual total costs were highest ($8512) for nociceptive pain with a neuropathic component with prior nociceptive pain (n=9162 employees), $7126 for nociceptive pain with a neuropathic component with no prior nociceptive pain (n=5172), $5574 for nociceptive pain only (n=35,347), and $3017 for control employees with no back or neck pain diagnosis (n=226,683). Medical, short-term disability, and prescription drugs yielded the highest incremental costs compared to controls. Mean total absence days/year were 8.26, 7.86, 5.70, and 3.44, respectively. The economic burden of back pain or neck pain is increased when associated with a neuropathic component.

  1. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain.

    Science.gov (United States)

    Guasti, Leonardo; Richardson, Denise; Jhaveri, Maulik; Eldeeb, Khalil; Barrett, David; Elphick, Maurice R; Alexander, Stephen P H; Kendall, David; Michael, Gregory J; Chapman, Victoria

    2009-07-01

    Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P pain states.

  2. Chronic Pain: Symptoms, Diagnosis, & Treatment

    Science.gov (United States)

    ... in the treatment. Treatment With chronic pain, the goal of treatment is to reduce pain and improve ... some treatments used for chronic pain. Less invasive psychotherapy, relaxation therapies, biofeedback, and behavior modification may also ...

  3. Clinical use of pregabalin in the management of central neuropathic pain

    Directory of Open Access Journals (Sweden)

    Nanna B Finnerup

    2007-01-01

    Full Text Available Nanna B Finnerup, Troels S JensenDanish Pain Research Center, Department of Neurology, Aarhus University Hospital, Aarhus, DenmarkAbstract: Central neuropathic pain (central pain is treated with antidepressants, various anticonvulsants, opioids, and cannabinoids, but in many cases treatment is insufficient and associated with a range of side-effects. This review addresses a new treatment for neuropathic pain, the anticonvulsant pregabalin. We review the pharmacology, mode of action, pharmacokinetics, and safety of pregabalin as well as two randomized efficacy studies in central pain and a brief overview of efficacy in peripheral neuropathic pain. Pregabalin appears to have efficacy in treating central pain comparable to that in peripheral neuropathic pain as well as efficacy of other recommended drugs for central pain. Pregabalin also improves disturbed sleep and anxiety. Pregabalin is well tolerated; the most common side-effects are somnolence, dizziness, ataxia, and weight gain. Pregabalin is suitable for patients on multiple drugs although there may be additive CNS-related side-effects. Thus, pregabalin has a primary role in central pain patients.Keywords: central pain, neuropathic pain, pregabalin, pharmacology

  4. Mechanisms of disease: mechanism-based classification of neuropathic pain - a critical analysis

    DEFF Research Database (Denmark)

    Finnerup, Nanna Brix; Jensen, Troels Staehelin

    2006-01-01

    Classification of neuropathic pain according to etiology or localization has clear limitations. The discovery of specific molecular and cellular events following experimental nerve injury has raised the possibility of classifying neuropathic pain on the basis of the underlying neurobiological...... mechanisms. Application of this approach in the clinic is problematic, however, owing to a lack of precise tools to assess symptoms and signs, and difficulties in correlating symptoms and signs with mechanisms. Development and validation of diagnostic methods to identify mechanisms, together...... with pharmacological agents that specifically target these mechanisms, seems to be the most logical and rational way of improving neuropathic pain treatment....

  5. Neuropathic pain and psychological morbidity in patients with treated leprosy: a cross-sectional prevalence study in Mumbai.

    Directory of Open Access Journals (Sweden)

    Estrella Lasry-Levy

    Full Text Available BACKGROUND: Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity. CONCLUSIONS/SIGNIFICANCE: One hundred and one patients were recruited, and 22 (21.8% had neuropathic pain. The main sensory symptoms were numbness (86.4%, tingling (68.2%, hypoesthesia to touch (81.2% and pinprick (72.7%. Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity.

  6. Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain

    OpenAIRE

    Zhang, Yu-Qiu; Guo, Ning; Peng, Guangdun; Han, Mei; Raincrow, Jeremy; Chiu, Chi-hua; Coolen, Lique M.; Wenthold, Robert J.; Zhao, Zhi-Qi; Jing, Naihe; Yu, Lei

    2009-01-01

    Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in dorsal horn laminae where peripheral nociceptive inputs first synapse, colocalizing with nociception-related neuropeptides CGRP and substance P. With ...

  7. Inhibition of glycogen synthase kinase 3β activity with lithium prevents and attenuates paclitaxel-induced neuropathic pain.

    Science.gov (United States)

    Gao, M; Yan, X; Weng, H-R

    2013-12-19

    Paclitaxel (taxol) is a first-line chemotherapy-drug used to treat many types of cancers. Neuropathic pain and sensory dysfunction are the major toxicities, which are dose-limiting and significantly reduce the quality of life in patients. Two known critical spinal mechanisms underlying taxol-induced neuropathic pain are an increased production of pro-inflammatory cytokines including interleukin-1β (IL-1β) and suppressed glial glutamate transporter activities. In this study, we uncovered that increased activation of glycogen synthase kinase 3beta (GSK3β) in the spinal dorsal horn was concurrently associated with increased protein expressions of GFAP, IL-1β and a decreased protein expression of glial glutamate transporter 1 (GLT-1), as well as the development and maintenance of taxol-induced neuropathic pain. The enhanced GSK3β activities were supported by the concurrently decreased AKT and mTOR activities. The changes of all these biomarkers were basically prevented when animals received pre-emptive lithium (a GSK3β inhibitor) treatment, which also prevented the development of taxol-induced neuropathic pain. Further, chronic lithium treatment, which began on day 11 after the first taxol injection, reversed the existing mechanical and thermal allodynia induced by taxol. The taxol-induced increased GSK3β activities and decreased AKT and mTOR activities in the spinal dorsal horn were also reversed by lithium. Meanwhile, protein expressions of GLT-1, GFAP and IL-1β in the spinal dorsal horn were improved. Hence, suppression of spinal GSK3β activities is a key mechanism used by lithium to reduce taxol-induced neuropathic pain, and targeting spinal GSK3β is an effective approach to ameliorate GLT-1 expression and suppress the activation of astrocytes and IL-1β over-production in the spinal dorsal horn.

  8. Pregabalin, the lidocaine plaster and duloxetine in patients with refractory neuropathic pain: a systematic review

    Directory of Open Access Journals (Sweden)

    Budhia Sangeeta

    2010-11-01

    Full Text Available Abstract Background Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP. This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2nd line or later in UK patients with neuropathic pain. Methods A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed. Results Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design. Conclusions Little evidence is available relevant to the

  9. Dental impaction pain model as a potential tool to evaluate drugs with efficacy in neuropathic pain.

    Science.gov (United States)

    Malmstrom, Kerstin; Kotey, Paul; McGratty, Megan; Ramakrishnan, Rohini; Gottesdiener, Keith; Reicin, Alise; Wagner, John A

    2006-08-01

    Intravenous lidocaine, a nonspecific Na-channel blocker, was used to assess the dental impaction model for evaluation of neuropathic pain drugs. Sixty patients, experiencing moderate or severe pain after removal of > or = 2 third molars, were randomized (2:2:1:1) to lidocaine (4 mg/kg; maximal dose 300 mg), oxycodone/acetaminophen (10/650 mg), placebo, and active placebo (diphenhydramine, 50 mg). Lidocaine provided a modest degree of pain relief. Predefined endpoints of total pain relief and sum of pain intensity at 2, 4, and 6 hours showed numerically, not statistically significantly, greater pain relief versus placebo. A significantly greater effect over placebo was observed in peak effect and at shorter time points (30 minutes and 1 hour), consistent with the pharmacokinetic profile (plasma concentration of approximately 2 mug/mL). Oxycodone/acetaminophen provided significantly greater analgesia versus placebo, validating study conduct, and significantly greater pain relief was observed versus lidocaine, which is consistent with a smaller portion of dental extraction pain being of neuropathic origin. PMID:16855076

  10. Effects of Melatonin and Vitamin E on Peripheral Neuropathic Pain in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Reza Heidari

    2010-04-01

    Full Text Available Objective(sPrevious studies have indicated that diabetes mellitus might be accompanied by neuropathic pain. Oxidative stress is implicated as a final common pathway in development of diabetic neuropathy. Pharmacological interventions targeted at inhibiting free radical production have shown beneficial effects in diabetic neuropathy. The aim of this study was to investigate and compare the possible analgesic effects of melatonin and vitamin E in diabetic rats.Materials and MethodsThis study was performed on 32 male Wistar rats divided into 4 groups: control, diabetic, melatonin-treated diabetic and vitamin E-treated diabetic. Experimental diabetes was induced by intraperitoneal streptozotocin (50 mg/kg injection. Melatonin (10 mg/kg, i.p. and vitamin E (100 mg/kg, i.p. were injected for 2 weeks after 21st day of diabetes induction. At the end of administration period, pain-related behavior was assessed using 0.5% formalin test according to two spontaneous flinching and licking responses. The levels of lipid peroxidation as well as glutathione-peroxidase and catalase activities were evaluated in lumbosacral dorsal root ganglia.ResultsFormalin-evoked flinching and total time of licking were increased in both acute and chronic phases of pain in diabetic rats as compared to control rats, whereas treatment with melatonin or vitamin E significantly reduced the pain indices. Furthermore, lipid peroxidation levels increased and glutathione-peroxidase and catalase activities decreased in diabetic rats. Both antioxidants reversed the biochemical parameters toward their control values.ConclusionThese results suggest that oxidative stress may contribute to induction of pain in diabetes and further suggest that antioxidants, melatonin and vitamin E, can reduce peripheral neuropathic pain in streptozotocin-induced diabetic rats.

  11. Minocycline Effects on IL-6 Concentration in Macrophage and Microglial Cells in a Rat Model of Neuropathic Pain

    Science.gov (United States)

    Moini-Zanjani, Taraneh; Ostad, Seyed-Nasser; Labibi, Farzaneh; Ameli, Haleh; Mosaffa, Nariman; Sabetkasaei, Masoumeh

    2016-01-01

    Background: Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury (CCI) model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells. Methods: Male Wistar rat (n=6, 150-200 g) were divided into three different groups: 1) CCI+vehicle, 2) sham+vehicle, and 3) CCI+drug. Minocycline (10, 20, and 40 mg/kg) was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 (before surgery) and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz’s media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h. Results: Minocycline (10, 20, and 40 mg/kg) attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals. Conclusion: Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells. PMID:27221523

  12. R-flurbiprofen reduces neuropathic pain in rodents by restoring endogenous cannabinoids.

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    Philipp Bishay

    Full Text Available BACKGROUND: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB, which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARgamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. CONCLUSION: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain.

  13. R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids

    Science.gov (United States)

    Marian, Claudiu; Häussler, Annett; Wijnvoord, Nina; Ziebell, Simone; Metzner, Julia; Koch, Marco; Myrczek, Thekla; Bechmann, Ingo; Kuner, Rohini; Costigan, Michael; Dehghani, Faramarz; Geisslinger, Gerd; Tegeder, Irmgard

    2010-01-01

    Background R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPARγ and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain. PMID:20498712

  14. Antinociceptive effects of fisetin against diabetic neuropathic pain in mice: Engagement of antioxidant mechanisms and spinal GABAA receptors.

    Science.gov (United States)

    Zhao, Xin; Li, Xin-Lin; Liu, Xin; Wang, Chuang; Zhou, Dong-Sheng; Ma, Qing; Zhou, Wen-Hua; Hu, Zhen-Yu

    2015-12-01

    Peripheral painful neuropathy is one of the most common complications in diabetes and necessitates improved treatment. Fisetin, a naturally occurring flavonoid, has been reported to exert antidepressant-like effect in previous studies. As antidepressant drugs are employed clinically to treat neuropathic pain, this work aimed to investigate whether fisetin possess beneficial effect on diabetic neuropathic pain and explore the mechanism(s). We subjected mice to diabetes by a single intraperitoneal (i.p.) injection of streptozotocin (200mg/kg), and von Frey test or Hargreaves test was used to assess mechanical allodynia or thermal hyperalgesia, respectively. Chronic treatment of diabetic mice with fisetin not only ameliorated the established symptoms of thermal hyperalgesia and mechanical allodynia, but also arrested the development of neuropathic pain when given at low doses. Although chronic fisetin administration did not impact on the symptom of hyperglycemia in diabetic mice, it reduced exacerbated oxidative stress in tissues of spinal cord, dorsal root ganglion (DRG) and sciatic verve. Furthermore, the analgesic actions of fisetin were abolished by repetitive co-treatment with the reactive oxygen species (ROS) donor tert-butyl hydroperoxide (t-BOOH), but potentiated by the ROS scavenger phenyl-N-tert-butylnitrone (PBN). Finally, acute blockade of spinal GABAA receptors by bicuculline totally counteracted such fisetin analgesia. These findings indicate that chronic fisetin treatment can delay or correct neuropathic hyperalgesia and allodynia in mice with type 1 diabetes. Mechanistically, the present fisetin analgesia may be associated with its antioxidant activity, and spinal GABAA receptors are likely rendered as downstream targets. PMID:26520392

  15. Effects of silymarin on neuropathic pain and formalin-induced nociception in mice

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    Faezeh Vahdati Hassani

    2015-07-01

    Conclusion:Results of the present study indicated that repeated administration of silymarin prevents the formalin-induced nociceptive behavior. However, it is not effective in the treatment of sciatic neuropathic pain.

  16. Chronic pain disrupts the reward circuitry in multiple sclerosis.

    Science.gov (United States)

    Seixas, Daniela; Palace, Jacqueline; Tracey, Irene

    2016-08-01

    Pain commonly affects multiple sclerosis (MS) patients, and has the potential to become chronic and burden an already damaged central nervous system. Imaging studies are providing insights into brain restructuring associated with chronic pain and different chronic pain conditions seem to evoke distinct plasticity patterns. Our objective was to study the structural and functional brain changes of chronic neuropathic pain of MS. Employing structural and resting functional magnetic resonance imaging we compared MS patients with chronic central pain with MS patients without pain matched with respect to age, gender, subtype and duration of MS and disability. Mean duration of pain was 7.6 years. Comparing the pain and no-pain groups, brain functional default-mode network differences were found. There was decreased coactivation in the caudate nucleus and nucleus accumbens bilaterally. Also, for the relapsing-remitting subgroup of patients, grey matter thickness changes predominated in the pain group in the mesial region of the temporal lobes, caudate, putamen, thalami and the fronto-parietal cortex; in the group without pain, changes predominated in the frontopolar and orbitofrontal cortices and in the occipital areas. A dysfunction in the reward system in chronic pain of MS was found, particularly in the brain areas involved in its motivational aspects, as such probably reflecting the maladaptive physiology of chronic pain, and possibly the signature of pain in MS, in a disease where reward impairment seems to be already one of its features. PMID:27178661

  17. CB1 receptors modulate affective behaviour induced by neuropathic pain.

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    Rácz, Ildikó; Nent, Elisa; Erxlebe, Edda; Zimmer, Andreas

    2015-05-01

    Patients suffering from chronic pain are often diagnosed with a psychiatric condition, in particular generalized anxiety and major depression. The underlying pathomechanisms contributing to this comorbidity, however, are not entirely clear. In this manuscript we have focussed on the potential role of the cannabinoid receptor CB1, because it is known to modulate neuronal circuits contributing to chronic pain states and affective behaviours. For this purpose we analysed the consequences of a partial sciatic nerve ligation on anxiety- and depression-related behaviours in mice lacking CB1 receptors. Our results show that the development of mechanical hypersensitivity was similar in CB1 deficient mice and wild type controls. However, CB1 knockouts showed much more pronounced behavioural manifestations of anxiety-related behaviours in the light-dark and zero-maze tests, sucrose anhedonia, and disturbed home-cage activity. These results indicate that the endocannabinoid system affects chronic pain-induced mood changes through CB1 receptors.

  18. Effect of DSP4 and desipramine in the sensorial and affective component of neuropathic pain in rats.

    Science.gov (United States)

    Bravo, Lidia; Mico, Juan A; Rey-Brea, Raquel; Camarena-Delgado, Carmen; Berrocoso, Esther

    2016-10-01

    Previous findings suggest that neuropathic pain induces characteristic changes in the noradrenergic system that may modify the sensorial and affective dimensions of pain. We raise the hypothesis that different drugs that manipulate the noradrenergic system can modify specific domains of pain. In the chronic constriction injury (CCI) model of neuropathic pain, the sensorial (von Frey and acetone tests) and the affective (place escape/avoidance paradigm) domains of pain were evaluated in rats 1 and 2weeks after administering the noradrenergic neurotoxin [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] (DSP4, 50mg/kg). In other animals, we evaluated the effect of enhancing noradrenergic tone in the 2weeks after injury by administering the antidepressant desipramine (10mg/kg/day, delivered by osmotic minipumps) during this period, a noradrenaline reuptake inhibitor. Moreover, the phosphorylation of the extracellular signal regulated kinases (p-ERK) in the anterior cingulate cortex (ACC) was also assessed. The ACC receives direct inputs from the main noradrenergic nucleus, the locus coeruleus, and ERK activation has been related with the expression of pain-related negative affect. These studies revealed that DSP4 almost depleted noradrenergic axons in the ACC and halved noradrenergic neurons in the locus coeruleus along with a decrease in the affective dimension and an increased of p-ERK in the ACC. However, it did not modify sensorial pain perception. By contrast, desipramine reduced pain hypersensitivity, while completely impeding the reduction of the affective pain dimension and without modifying the amount of p-ERK. Together results suggest that the noradrenergic system may regulate the sensorial and affective sphere of neuropathic pain independently. PMID:27181607

  19. Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

    Science.gov (United States)

    Pellicer, Francisco; López-Muñoz, Francisco J.

    2016-01-01

    Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D2, GABAA, and opioids, but not by 5-HT1A, receptors. PMID:27672659

  20. In vivo and in vitro protective effects of omeprazole against neuropathic pain.

    Science.gov (United States)

    Chanchal, Sanjay K; Mahajan, Umesh B; Siddharth, Sumit; Reddy, Navyya; Goyal, Sameer N; Patil, Prakash H; Bommanahalli, Basavaraj P; Kundu, Chanakya N; Patil, Chandragouda R; Ojha, Shreesh

    2016-01-01

    Apart from reducing the acid secretion, omeprazole inhibits activation of the nuclear factor-κB, release of inflammatory cytokines, and chemotaxis of neutrophils. These mechanisms prompted us to evaluate antineuropathic effect of omeprazole in the chronic constriction injury (CCI)-induced rat model of neuropathic pain and LPS mediated ROS-induced U-87 cells. Omeprazole at 50 mg/kg/day/oral for 14 days significantly reduced the intensity of neuropathic pain estimated as paw withdrawal latency, withdrawal pressure threshold and restored the motor nerve conduction velocity in the constricted nerve, when compared with respective groups. The histological findings revealed the protective effect of omeprazole against the CCI-induced damage. Omeprazole significantly decreased the levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) as compared to their respective control groups. It also reduced the oxidative stress by up regulating the SOD, catalase activity and decreasing MDA content. Similarly, in-vitro study, LPS mediated ROS-induced U-87 cells, omeprazole reduced the oxidative stress as well as the release of TNF-α, IL-1β and IL-6. Altogether, these results suggest that, neuroprotective effect of omeprazole is mediated through preventing release of proinflammatory cytokines, augmenting endogenous anti-oxidant defense system, and maintain the structural integrity of sciatic nerve from the CCI-induced structural damage and inflammatory changes. PMID:27435304

  1. Ethanolic extract of Aloe vera ameliorates sciatic nerve ligation induced neuropathic pain

    OpenAIRE

    Swetha Kanyadhara; Sujatha Dodoala; Sunitha Sampathi; Priyanka Punuru; Gopichand Chinta

    2014-01-01

    Background: Aloe vera is being used since ages by human kind for treating various ailments including various inflammatory conditions, but scientific validation has not been done for analgesic activity against neuropathic pain. Objective: The current study was designed to systematically evaluate the therapeutic potential of the ethanolic extract of A. vera (EEAV) against sciatic nerve ligation (SCNL) induced neuropathic pain. Materials and Methods: Nociceptive threshold of EEAV against...

  2. Nerve Regenerative Effects of GABA-B Ligands in a Model of Neuropathic Pain

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    Valerio Magnaghi

    2014-01-01

    Full Text Available Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL- induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg and CGP56433 (3 mg/kg alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22 expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.

  3. 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.

  4. Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain.

    Science.gov (United States)

    Liu, Yu; Tang, Jianguang; Zhang, Yunxiao; Xun, Xiaohong; Tang, Dongfang; Peng, Dezheng; Yi, Jianming; Liu, Zhonghua; Shi, Xiaoliu

    2014-08-01

    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. PMID:25123556

  5. Lipo-endomorphin-1 derivatives with systemic activity against neuropathic pain without producing constipation.

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    Pegah Varamini

    Full Text Available To enhance the drug-like properties of the endogenous opioid peptide endomorphin-1 (1 = Tyr-Pro-Trp-Phe-NH(2, the N-terminus of the peptide was modified with 2-aminodecanoic acid, resulting in compound 3. Tyr in compound 1 was replaced with 2,6-dimethyltyrosine yielding compound 2. Derivative 2 was also substituted with 2-aminodecanoic acid producing compound, 4. Lipoamino acid-modified derivatives showed improved metabolic stability and membrane permeability while maintaining high μ-opioid (MOP receptor binding affinity and acting as a potent agonist. In vivo studies showed dose-dependent antinociceptive activity following intravenous (i.v. administration of compounds 3 and 4 in a chronic constriction injury (CCI-rat model of neuropathic pain with ED(50 values of 1.22 (± 0.93 and 0.99 (± 0.89 µmol/kg, respectively. Pre-treatment of animals with naloxone hydrochloride significantly attenuated the anti-neuropathic effects of compound 3, confirming the key role of opioid receptors in mediating antinociception. In contrast to morphine, no significant constipation was produced following i.v. administration of compound 3 at 16 µmol/kg. Furthermore, following chronic administration of equi-potent doses of compound 3 and morphine to rats, there was less antinociceptive tolerance for compound 3 compared with morphine.

  6. Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

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    Schmitz Beate

    2008-08-01

    Full Text Available Abstract Background Ample evidence suggests a substantial contribution of cellular and molecular changes in the spinal cord to the induction and persistence of chronic neuropathic pain conditions. While for a long time, proteases were mainly considered as protein degrading enzymes, they are now receiving growing interest as signalling molecules in the pain pathology. In the present study we focused on two cathepsins, CATS and CATX, and studied their spatiotemporal expression and activity during the development and progression of neuropathic pain in the CNS of the rat 5th lumbar spinal nerve transection model (L5T. Results Immediately after the lesion, both cathepsins, CATS and CATX, were upregulated in the spinal cord. Moreover, we succeeded in measuring the activity of CATX, which was substantially increased after L5T. The differential expression of these proteins exhibited the same spatial distribution and temporal progression in the spinal cord, progressing up to the medulla oblongata in the late phase of chronic pain. The cellular distribution of CATS and CATX was, however, considerably different. Conclusion The cellular distribution and the spatio-temporal development of the altered expression of CATS and CATX suggest that these proteins are important players in the spinal mechanisms involved in chronic pain induction and maintenance.

  7. Prevalence of Neuropathic Pain in Radiotherapy Oncology Units

    International Nuclear Information System (INIS)

    Purpose: Neuropathic pain (NP) in cancer patients severely impacts quality of life. Radiotherapy (RT) may cause NP, and at the same time, cancer patients visit RT units for pain relief. NP prevalence at these sites and current analgesic treatment should be assessed to improve management. Methods and Materials: This epidemiological, prospective, multicenter study was undertaken to assess NP prevalence, according to Douleur Neuropathique 4 questions questtionaire (DN4) test results, and analgesic management in cancer pain patients visiting RT oncologic units. Secondary analyses assessed NP etiology and pain intensity (using the Brief Pain Inventory-Short Form) and impact (using the Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study [MOS] for Sleep, and the Health Survey Short Form-12). Results: A total of 1,098 patients with any kind of pain were registered. NP prevalence was 31.1% (95% confidence interval, 28.4%--33.9%); 291 NP patients (mean age, 62.2 ±12.5 years and 57.7% men) were eligible for study; 49% of patients were overweight. The most frequent tumors were those of breast and lung, and stage IIIB was the most common cancer stage. The tumors caused 75% of NP cases. Anxiety, sleepiness, and depression were common. At 8 weeks, pain intensity and interference with daily activities decreased significantly for 50.8% of responders. Depression and anxiety (p < 0.0001) scores on the Physical Component Summary and Mental Component Summary measures (p < 0.0001) and all MOS-Sleep subscales, except for snoring, improved significantly. The percentage of satisfied patients increased from 13.8% to 87.4% (p < 0.0001) with the current analgesic treatment, which meant a 1.2- and 6-fold increase (p < 0.0001) in narcotic analgesics and anticonvulsants, respectively, compared to previous treatment. Conclusions: NP is highly prevalent at RT oncology units, with sleepiness, anxiety, and depression as frequent comorbidities. There is a need to improve management

  8. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

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    Elphick Maurice R

    2009-07-01

    Full Text Available Abstract Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG, and the related compound N-palmitoylethanolamine (PEA, in neuropathic spinal cord. Selective spinal nerve ligation (SNL in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P P P P P

  9. Prevalence, Causes, and Treatment of Neuropathic Pain in Dutch Nursing Home Residents : A Retrospective Chart Review

    NARCIS (Netherlands)

    van Kollenburg, Esther G. P.; Lavrijsen, Jan C. M.; Verhagen, Stans C.; Zuidema, Sytse U.; Schalkwijk, Annelies; Vissers, Kris C. P.

    2012-01-01

    Objectives To identify the prevalence and causes of neuropathic pain in Dutch nursing home residents; to establish the prevalence of painful and nonpainful diabetic polyneuropathy in a subsample of individuals with diabetes mellitus and central poststroke pain (CPSP) in a subsample of individuals wh

  10. Neuropathic pain in patients with spinal cord injury: report of 213 patients

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    Manoel Jacobsen Teixeira

    2013-09-01

    Full Text Available Objective Management of neuropathic pain following spinal cord injury (SCI can be a frustrating experience for patients since it poses a therapeutic challenge. In this article the authors describe the clinical characteristics of a group of patients with pain after spinal cord injury. Methods In this retrospective study, 213 patients with SCI and neuropathic pain were assessed. We analyzed clinical characteristics, treatment options, and pain intensity for these patients. Results The main cause of SCI was spine trauma, which occurred in 169 patients, followed by tumors and infection. Complete lesions were verified in 144 patients. In our study, patients with traumatic SCI and partial lesions seem to be presented with more intense pain; however, this was not statistically significant. Conclusions Neuropathic pain is a common complaint in patients with SCI and presents a treatment challenge. Knowledge of the clinical characteristics of this group of patients may help determine the best approach to intervention.

  11. Effects of curcumin on sodium currents of dorsal root ganglion neurons in type 2 diabetic neuropathic pain rats.

    Science.gov (United States)

    Meng, Bo; Shen, Lu-lu; Shi, Xiao-ting; Gong, Yong-sheng; Fan, Xiao-fang; Li, Jun; Cao, Hong

    2015-11-01

    Along with the development of economy and society, type 2 diabetic mellitus (T2DM) has become one of the most common diseases at the global level. As one of the complications of T2DM, diabetic neuropathic pain (DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion (DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels (VGSCs) and the increased sodium currents (I(Na)). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2DM and its various complications including DNP effectively. The present study demonstrates that the I(Na) of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin. PMID:27215022

  12. Analgesic Effect of Harpagophytum procumbens on Postoperative and Neuropathic Pain in Rats

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    Dong Wook Lim

    2014-01-01

    Full Text Available Harpagophytum procumbens, also known as Devil’s Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesic effects in plantar incision and spared nerve injury (SNI rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs. The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22–27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesic effects in the case of acute postoperative pain and chronic neuropathic pain in rats.

  13. Analgesic effect of Harpagophytum procumbens on postoperative and neuropathic pain in rats.

    Science.gov (United States)

    Lim, Dong Wook; Kim, Jae Goo; Han, Daeseok; Kim, Yun Tai

    2014-01-01

    Harpagophytum procumbens, also known as Devil's Claw, has historically been used to treat a wide range of conditions, including pain and arthritis. The study was designed to investigate whether H. procumbens extracts exhibit analgesic effects in plantar incision and spared nerve injury (SNI) rats. The whole procedure was performed on male SD rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) test measured by von Frey filaments. Pain-related behavior was also determined through analysis of ultrasonic vocalization (USVs). The results of experiments showed MWT values of the group that was treated with 300 mg/kg H. procumbens extract increased significantly; on the contrary, the number of 22-27 kHz USVs of the treated group was reduced at 6 h and 24 h after plantar incision operation. After 21 days of continuous treatment with H. procumbens extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity responses by MWT, compared with the control group. These results suggest that H. procumbens extracts have potential analgesic effects in the case of acute postoperative pain and chronic neuropathic pain in rats. PMID:24441655

  14. Antinociceptive Effects of Botulinum Toxin Type A on Trigeminal Neuropathic Pain.

    Science.gov (United States)

    Yang, K Y; Kim, M J; Ju, J S; Park, S K; Lee, C G; Kim, S T; Bae, Y C; Ahn, D K

    2016-09-01

    Previous studies have demonstrated that botulinum toxin type A (BoNT-A) attenuates orofacial nociception. However, there has been no evidence of the participation of the voltage-gated sodium channels (Navs) in the antinociceptive mechanisms of BoNT-A. This study investigated the cellular mechanisms underlying the antinociceptive effects of BoNT-A in a male Sprague-Dawley rat model of trigeminal neuropathic pain produced by malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by a miniature dental implant placement to induce injury to the inferior alveolar nerve. Mechanical allodynia was monitored after subcutaneous injection of BoNT-A at 3, 7, or 12 d after malpositioned dental implant surgery. Subcutaneous injections of 1 or 3 U/kg of BoNT-A on postoperative day 3 significantly attenuated mechanical allodynia, although 0.3 U/kg of BoNT-A did not affect the air-puff threshold. A single injection of 3 U/kg of BoNT-A produced prolonged antiallodynic effects over the entire experimental period. Treatment with BoNT-A on postoperative days 7 and 12, when pain had already been established, also produced prolonged antiallodynic effects. Double treatments with 1 U/kg of BoNT-A produced prolonged, more antiallodynic effects as compared with single treatments. Subcutaneous administration of 3 U/kg of BoNT-A significantly inhibited the upregulation of Nav isoform 1.7 (Nav1.7) expression in the trigeminal ganglion in the nerve-injured animals. These results suggest that antinociceptive effects of BoNT-A are mediated by an inhibition of upregulated Nav1.7 expression in the trigeminal ganglion. BoNT-A is therefore a potential new therapeutic agent for chronic pain control, including neuropathic pain. PMID:27418174

  15. Higher pain perception and lack of recovery from neuropathic pain in females: a behavioural, immunohistochemical, and proteomic investigation on sex-related differences in mice.

    Science.gov (United States)

    Vacca, Valentina; Marinelli, Sara; Pieroni, Luisa; Urbani, Andrea; Luvisetto, Siro; Pavone, Flaminia

    2014-02-01

    In experimental and clinical pain studies, the sex of subjects was rarely taken into account, even if nociceptive inputs appear to be processed and modulated by partially distinct neural mechanisms in each sex. In this study we analysed, in male and female mice, behavioural and neuronal responses in developing, maintaining, and recovering from neuropathic pain. Experiments were carried out in adult CD1 mice by using Chronic Constriction Injury (CCI) as neuropathic pain model. We investigated the temporal trend of mechanical nociceptive threshold together with functional recovery of the injured paw, and the immunofluorescence staining of proteins associated with nerve injury and repair and with spinal gliosis, 7 and 121days after CCI. A proteomic analysis on proteins extracted from sciatic nerves was also performed. Male mice showed a gradual decrease of CCI-induced allodynia, the complete recovery occurring 81days after the sciatic nerve ligation. On the contrary, in female mice, allodynia was still present 121days after CCI. Sex-dependent differences also resulted from immunofluorescence experiments: in sciatic nerve, the expression of P0 and Neu200 is greater in neuropathic males than in neuropathic females, suggesting faster nerve regeneration. Proteomic analysis confirmed sex-related differences of proteins associated with nerve regenerative processes. In addition, the reactive gliosis induced by CCI at day 7, as revealed by colocalization of glial fibrillary acidic protein (astrocytes) and CD11b (microglia) with phosphorylated p38, disappeared 121 days after CCI in male but not in female mice. These results may have important therapeutic implications for the treatment of neuropathic pain.

  16. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... manageable, but chronic pain is different. And because it is different, we need to think about it in very different ways. Ed Covington, M.D.: ... no apparent physical injury or illness to explain it. The physician and the patient are accustomed to ...

  17. Acetaminophen for Chronic Pain

    DEFF Research Database (Denmark)

    Ennis, Zandra Nymand; Dideriksen, Dorthe; Vaegter, Henrik Bjarke;

    2016-01-01

    conducted according to PRISMA guidelines. All studies were conducted in patients with hip- or knee osteoarthritis and six out of seven studies had observation periods of less than three months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little......Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first-line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search...... evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended. This article is protected by copyright. All rights reserved....

  18. Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory

    Directory of Open Access Journals (Sweden)

    de Andrade Daniel

    2011-11-01

    Full Text Available Abstract Backgroud It has been shown that different symptoms or symptom combinations of neuropathic pain (NeP may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI is able to detect distinct clusters of symptoms (i.e. dimensions with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV of the NPSI. Methods Patients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i rate their mean pain intensity in the last 24 hours on an 11-point (0-10 numerical scale; (ii complete the PV-NPSI; (iii provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC were filled out in the second visit. Results PV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms. Conclusions The psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

  19. Current trends in the diagnosis and management of post-herniorraphy chronic groin pain

    OpenAIRE

    2011-01-01

    Inguinodynia (chronic groin pain) is one of the recognised complications of the commonly performed Lichtenstein mesh inguinal hernia repair. This has major impact on quality of life in a significant proportion of patients. The pain is classified as neuropathic and non-neuropathic related to nerve damage and to the mesh, respectively. Correct diagnosis of this problem is relatively difficult. A thorough history and clinical examination are essential, as is a good knowledge of the groin nerve d...

  20. HSV gene transfer in the treatment of chronic pain

    Institute of Scientific and Technical Information of China (English)

    David J. Fink; Marina Mata

    2008-01-01

    It has proven difficult to use systemic administration of small molecules to selectively modulate nociception. Over the past decade, we and others have developed non-replicating herpes simplex virus (HSV)-based vectors to treat chronic pain. Subcutaneous inoculation of an HSV vector effectively transduces sensory neurons in the dorsal root ganglion; release of transgene-coded inhibitory neurotransmitters or anti-inflammatory peptides reduces pain-related behaviors in rodent models of chronic inflammatory and neuro-pathic pain. A phase 1 trial of this therapy in patients is set to begin soon.

  1. Neuropathic Itch

    OpenAIRE

    Oaklander, Anne Louise

    2011-01-01

    Chronic itch can be caused by dysfunctions of itch-sensing neurons that produce sensory hallucinations of pruritogenic stimuli. The cellular and molecular mechanisms are still unknown. All neurological disease categories have been implicated and neurological causes should be considered for patients with otherwise-unexplained itch. The same neurological illnesses that cause neuropathic pain can also or instead cause itch. These include shingles (particularly of the head or neck), small-fiber p...

  2. Dual Alleviation of Acute and Neuropathic Pain by Fused Opioid Agonist-Neurokinin 1 Antagonist Peptidomimetics.

    Science.gov (United States)

    Betti, Cecilia; Starnowska, Joanna; Mika, Joanna; Dyniewicz, Jolanta; Frankiewicz, Lukasz; Novoa, Alexandre; Bochynska, Marta; Keresztes, Attila; Kosson, Piotr; Makuch, Wioletta; Van Duppen, Joost; Chung, Nga N; Vanden Broeck, Jozef; Lipkowski, Andrzej W; Schiller, Peter W; Janssens, Frans; Ceusters, Marc; Sommen, François; Meert, Theo; Przewlocka, Barbara; Tourwé, Dirk; Ballet, Steven

    2015-12-10

    Herein, the synthesis and biological evaluation of dual opioid agonists-neurokinin 1 receptor (NK1R) antagonists is described. In these multitarget ligands, the two pharmacophores do not overlap, and this allowed maintaining high NK1R affinity and antagonist potency in compounds 12 and 13. Although the fusion of the two ligands resulted in slightly diminished opioid agonism at the μ- and δ-opioid receptors (MOR and DOR, respectively), as compared to the opioid parent peptide, balanced MOR/DOR activities were obtained. Compared to morphine, compounds 12 and 13 produced more potent antinociceptive effects in both acute (tail-flick) and neuropathic pain models (von Frey and cold plate). Similarly to morphine, analgesic tolerance developed after repetitive administration of these compounds. To our delight, compound 12 did not produce cross-tolerance with morphine and high antihyperalgesic and antiallodynic effects could be reinstated after chronic administration of each of the two compounds. PMID:26713106

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Boccella, Serena; Vacca, Valentina; Errico, Francesco; Marinelli, Sara; Squillace, Marta; Di Maio, Anna; Vitucci, Daniela; Palazzo, Enza; De Novellis, Vito; Maione, Sabatino; Pavone, Flaminia; Usiello, Alessandro

    2015-01-01

    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. PMID:25629055

  5. Colocalized structural and functional changes in the cortex of patients with trigeminal neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Alexandre F DaSilva

    Full Text Available BACKGROUND: Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness and functional (blood oxygenation dependent level - BOLD changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP affecting the right maxillary (V2 division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy. METHODOLOGY/PRINCIPAL FINDINGS: Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII, motor (MI and posterior insula, or emotional (DLPFC, Frontal, Anterior Insula, Cingulate processing of pain. Both structural and functional (to brush-induced allodynia scans were obtained and averaged from two different imaging sessions separated by 2-6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions. CONCLUSIONS: Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions.

  6. Neural mobilization reverses behavioral and cellular changes that characterize neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Santos Fabio M

    2012-07-01

    Full Text Available Abstract Background The neural mobilization technique is a noninvasive method that has proved clinically effective in reducing pain sensitivity and consequently in improving quality of life after neuropathic pain. The present study examined the effects of neural mobilization (NM on pain sensitivity induced by chronic constriction injury (CCI in rats. The CCI was performed on adult male rats, submitted thereafter to 10 sessions of NM, each other day, starting 14 days after the CCI injury. Over the treatment period, animals were evaluated for nociception using behavioral tests, such as tests for allodynia and thermal and mechanical hyperalgesia. At the end of the sessions, the dorsal root ganglion (DRG and spinal cord were analyzed using immunohistochemistry and Western blot assays for neural growth factor (NGF and glial fibrillary acidic protein (GFAP. Results The NM treatment induced an early reduction (from the second session of the hyperalgesia and allodynia in CCI-injured rats, which persisted until the end of the treatment. On the other hand, only after the 4th session we observed a blockade of thermal sensitivity. Regarding cellular changes, we observed a decrease of GFAP and NGF expression after NM in the ipsilateral DRG (68% and 111%, respectively and the decrease of only GFAP expression after NM in the lumbar spinal cord (L3-L6 (108%. Conclusions These data provide evidence that NM treatment reverses pain symptoms in CCI-injured rats and suggest the involvement of glial cells and NGF in such an effect.

  7. A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development

    Directory of Open Access Journals (Sweden)

    Wilkes D

    2012-10-01

    Full Text Available Denise Wilkes,1 Guangwen Li,2 Carmina F Angeles,3 Joel T Patterson,4 Li-Yen Mae Huang21Department of Anesthesiology, 2Department of Neuroscience and Cell Biology, 3Department of Neurosurgery University of Texas Medical Branch, Galveston, TX, USA; 4Neurospine Institute, Eugene, OR, USABackground: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans.Methods: A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats.Results: Peroneal nerve injury (PNI produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED50 for injured PNI hindlimb was 1.8-fold larger and Emax, the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models.Conclusion: PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain

  8. Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model.

    Science.gov (United States)

    Zhang, Enji; Yi, Min-Hee; Shin, Nara; Baek, Hyunjung; Kim, Sena; Kim, Eunjee; Kwon, Kisang; Lee, Sunyeul; Kim, Hyun-Woo; Chul Bae, Yong; Kim, Yonghyun; Kwon, O-Yu; Lee, Won Hyung; Kim, Dong Woon

    2015-01-01

    Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli. PMID:26109318

  9. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator

    NARCIS (Netherlands)

    Vanelderen, P.; Zundert, J. Van; Kozicz, L.T.; Puylaert, M.; Vooght, P. De; Mestrum, R.; Heylen, R.; Roubos, E.; Vissers, K.C.P.

    2015-01-01

    BACKGROUND: Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was not studied in humans with regard to the treatment of neuropathic pain. METHODS: In this randomized

  10. Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors

    Directory of Open Access Journals (Sweden)

    Ito Akitoshi

    2012-06-01

    Full Text Available Abstract Background The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Results Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG, which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. Conclusions These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.

  11. [Chronic pain in geriatrics].

    Science.gov (United States)

    Kennes, B

    2001-06-01

    Pain is frequent in communicative or no-communicative, ambulatory, institutionalized or hospitalized veterans. It is associated with severe comorbidity so much more than chronic pain could be neglected and expressed of atypical manner or masked by the absence of classical symptoms in particular in case of dementia or of sensory disorders. Pain detection by clinic examination or by pain assessment's methods and adequate approach by pharmacological and non pharmacological therapies are essential for correct pain management. On pharmacological plan, the strategy of the O.M.S. landings is applicable owing to a more particular attention to secondary effects and drugs interactions. AINS must be manipulated with prudence. There are no reasons to exclude opioides from the therapeutic arsenal but with a reduction of the starting doses, a regular adaptation and a very attentive survey. In drugs of landing 2, tramadol reveals itself as efficient and better tolerated as the codeine and dextropropoxyphene has to be to avoid. The obtaining of a satisfactory result depends on a regular assessment of the pain in a context of polydisciplinar approach (physicians, nurses, paramedicals, other care givers).

  12. Successful use of flupirtine in refractory neuropathic pain due to small fiber neuropathy.

    Science.gov (United States)

    Mishra, Seema; Choudhary, Prakash; Joshi, Saurabh; Bhatnagar, Sushma

    2013-02-01

    Small fiber neuropathy typically involves the small diameter nerve fibers, is usually idiopathic, and presents with peripheral pain. It can be excruciatingly painful at times despite the best of treatments. We present the case of a 22-year-old postoperative case of right frontoparietal oligodendroglioma who received multiple drugs for his severe neuropathic pain without significant relief. However, the pain almost completely subsided once flupirtine was added and substituted for some of the currently recommended first-line drugs. PMID:22495792

  13. A Mangifera indica L. Extract Could Be Used to Treat Neuropathic Pain and Implication of Mangiferin

    Directory of Open Access Journals (Sweden)

    María del C. Rabí

    2010-12-01

    Full Text Available It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α -induced IκB degradation and the binding of nuclear factor κB to DNA, which induces the transcription of genes implicated in the expression of some mediators and enzymes involved in inflammation, pain, oxidative stress and synaptic plasticity. In this paper we propose its potential utility in the neuropathic pain treatment. This hypothesis is supported in the cumulus of preclinical and clinical evidence around the extract and mangiferin, its major component, and speculates about the possible mechanism of action according to recent advances in the physiopathology of neuropathic pain.

  14. The lidocaine metabolite N-ethylglycine has antinociceptive effects in experimental inflammatory and neuropathic pain.

    Science.gov (United States)

    Werdehausen, Robert; Mittnacht, Sebastian; Bee, Lucy A; Minett, Michael S; Armbruster, Anja; Bauer, Inge; Wood, John N; Hermanns, Henning; Eulenburg, Volker

    2015-09-01

    Glycine transporter 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations and might thereby constitute a new drug target for the modulation of glycinergic inhibition in pain signaling. Consistent with this view, inhibition of GlyT1 has been found to induce antinociceptive effects in various animal pain models. We have shown previously that the lidocaine metabolite N-ethylglycine (EG) reduces GlyT1-dependent glycine uptake by functioning as an artificial substrate for this transporter. Here, we show that EG is specific for GlyT1 and that in rodent models of inflammatory and neuropathic pain, systemic treatment with EG results in an efficient amelioration of hyperalgesia and allodynia without affecting acute pain. There was no effect on motor coordination or the development of inflammatory edema. No adverse neurological effects were observed after repeated high-dose application of EG. EG concentrations both in blood and spinal fluid correlated with an increase of glycine concentration in spinal fluid. The time courses of the EG and glycine concentrations corresponded well with the antinociceptive effect. Additionally, we found that EG reduced the increase in neuronal firing of wide-dynamic-range neurons caused by inflammatory pain induction. These findings suggest that systemically applied lidocaine exerts antihyperalgesic effects through its metabolite EG in vivo, by enhancing spinal inhibition of pain processing through GlyT1 modulation and subsequent increase of glycine concentrations at glycinergic inhibitory synapses. EG and other substrates of GlyT1, therefore, may be a useful therapeutic agent in chronic pain states involving spinal disinhibition.

  15. Depletion of vesicular zinc in dorsal horn of spinal cord causes increased neuropathic pain in mice

    DEFF Research Database (Denmark)

    Jo, Seung; Danscher, Gorm; Schrøder, Henrik;

    2008-01-01

    neuropathic pain we applied Chung's rodent pain model on BALB/c mice, and traced zinc transporter 3 (ZnT3) proteins and zinc ions with immunohistochemistry and autometallography (AMG), respectively. Under anesthesia the left fifth lumbar spinal nerve was ligated in male mice in order to produced neuropathic...... pain. The animals were then sacrificed 5 days later. The ZnT3 immunoreactivity was found to have decreased significantly in dorsal horn of fourth, fifth, and sixth lumbar segments. In parallel with the depressed ZnT3 immunoreactivity the amount of vesicular zinc decreased perceptibly in superficial...

  16. What can rats tell us about neuropathic pain? Critical evaluation of behavioral tests used in rodent pain models

    OpenAIRE

    Sapunar, Damir; Puljak, Livia

    2009-01-01

    Background and Purpose: Animal models are a necessity in the study of neuropathic pain, and much of what we know about pain comes from studies in mice and rats. However, very few basic discoveries have been translated so far from rodent models into effective pain therapy. This review presents the most important rat models used in basic pain research, discusses their limitations and recommends better use of these models in future studies. Materials and Methods: A critical review of existin...

  17. The antinociceptive effects of ferulic acid on neuropathic pain: involvement of descending monoaminergic system and opioid receptors.

    Science.gov (United States)

    Xu, Ying; Lin, Dan; Yu, Xuefeng; Xie, Xupei; Wang, Liqun; Lian, Lejing; Fei, Ning; Chen, Jie; Zhu, Naping; Wang, Gang; Huang, Xianfeng; Pan, Jianchun

    2016-04-12

    Neuropathic pain can be considered as a form of chronic stress that may share common neuropathological mechanism between pain and stress-related depression and respond to similar treatment. Ferulic acid (FA) is a major active component of angelica sinensis and has been reported to exert antidepressant-like effects; however, it remains unknown whether FA ameliorate chronic constriction injury (CCI)-induced neuropathic pain and the involvement of descending monoaminergic system and opioid receptors. Chronic treatment with FA (20, 40 and 80 mg/kg) ameliorated mechanical allodynia and thermal hyperalgesia in von Frey hair and hot plate tasks, accompanied by increasing spinal noradrenaline (NA) and serotonin (5-HT) levels. Subsequent study suggested that treatment of CCI animals with 40 and 80 mg/kg FA also inhibited spinal MAO-A levels. FA's effects on mechanical allodynia or thermal hyperalgesiawas blocked by 6-hydroxydopamine (6-OHDA) or p-chlorophenylalanine (PCPA) via pharmacological depletion of spinal noradrenaline or serotonin. Moreover, the anti-allodynic action of FA on mechanical stimuli was prevented by pre-treatment with beta2-adrenoceptor antagonist ICI 118,551, or by the delta-opioid receptor antagonist naltrindole. While the anti-hyperalgesia on thermal stimuli induced by FA was blocked by pre-treatment with 5-HT1A receptor antagonist WAY-100635, or with the irreversible mu-opioid receptor antagonist beta-funaltrexamine. These results suggest that the effect of FA on neuropathic pain is potentially mediated via amelioration of the descending monoaminergic system that coupled with spinal beta2- and 5-HT1A receptors and the downstream delta- and mu-opioid receptors differentially. PMID:26967251

  18. Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients.

    Directory of Open Access Journals (Sweden)

    Andreas Binder

    Full Text Available Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K was associated with the presence of paradoxical heat sensation (p = 0.03, and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V with cold hypoalgesia (p = 0.0035. Two main subgroups characterized by preserved (1 and impaired (2 sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and pG (rs222747, M315I to cold hypaesthesia (p = 0.002, but there was absence of associations in subgroup 2. In this study we found no evidence that genetic

  19. Antinociceptive Effects of the Serotonin and Noradrenaline Reuptake Inhibitors Milnacipran and Duloxetine on Vincristine-Induced Neuropathic Pain Model in Mice

    OpenAIRE

    Katsuyama, Soh; Aso, Hiromu; Otowa, Akira; Yagi, Tomomi; Kishikawa, Yukinaga; Komatsu, Takaaki; Sakurada, Tsukasa; NAKAMURA, Hitoshi

    2014-01-01

    Vincristine is an anticancer drug used to treat a variety of cancer types, but it frequently causes peripheral neuropathy. Neuropathic pain is often associated with the appearance of abnormal sensory signs, such as allodynia. Milnacipran and duloxetine, serotonin/noradrenaline reuptake inhibitors, have shown efficacy against several chronic pain syndromes. In this study, we investigated the attenuation of vincristine-induced mechanical allodynia in mice by milnacipran and duloxetine. To induc...

  20. Neuronal-derived Ccl7 drives neuropathic pain by promoting astrocyte proliferation.

    Science.gov (United States)

    Ke, Bin Chang; Huang, Xia Xiao; Li, Yang; Li, Li Ya; Xu, Qin Xue; Gao, Yan; Liu, Yingju; Luo, Jie

    2016-08-01

    Recent studies suggest that peripheral nerve injury converts resting spinal cord astroglial cells into an activated state, which is required for the development and maintenance of neuropathic pain. However, the underlying mechanisms of how resting astrocytes are activated after nerve injury remain largely unknown. Astroglial cell proliferation and activation could be affected by endogenous factors including chemokines, growth factors, and neurotropic factor. Chemokine (C-C motif) ligand 7 (Ccl7) is essential in facilitating the development of neuropathic pain; however, the mechanism is unknown. In the present study, we found that Ccl7 promoted astrocyte proliferation and thus contributed toward neuropathic pain. Spinal nerve ligation increased the expression in the spinal cord of neuronal Ccl7. Behavioral analyses showed that knockdown of Ccl7 alleviated spinal nerve ligation-induced neuropathic pain. Further in-vitro study showed that neuronal-derived Ccl7 was sufficient for the proliferation and activation of astroglial cells. We found a novel mechanism of Ccl7 stimulating the proliferation and activation of spinal cord astrocytes that contributes toward neuropathic pain. PMID:27295026

  1. Unity vs. diversity of neuropathic pain mechanisms: Allodynia and hyperalgesia in rats selected for heritable predisposition to spontaneous pain.

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    Ziv-Sefer, Sagit; Raber, Pnina; Barbash, Shahar; Devor, Marshall

    2009-11-01

    Do contrasting neuropathic pain diagnoses share common pathophysiological mechanisms? Selective breeding was used to derive rat lines with a common genetic background but a striking difference in the degree of spontaneous pain behavior expressed in the neuroma model of neuropathic pain (HA rats (high autotomy) and LA rats (low autotomy)). The contrasting pain phenotype in these lines is attributable to allelic differences at a small number of genetic loci. Here we show that HA and LA rats also differ in their nocifensive response to applied stimuli in the Chung (spinal nerve ligation, SNL) model of neuropathic pain. This includes tactile allodynia and hyperalgesia, and heat allodynia. The degree of hypersensibility varied with sex, age at the time of nerve injury, and the extent of the nerve lesion. F1 crosses of HA and LA rats and inbred Lewis rats showed low levels of autotomy but variable levels of hypersensibility to applied stimuli. Results indicate that alleles which predispose to spontaneous neuropathic pain also predispose to stimulus-evoked pain (allodynia and hyperalgesia). This, in turn, suggests that despite contrasting etiology and behavioral endpoints, pain phenotype in the neuroma and the SNL models shares common pathophysiological mechanisms. PMID:19683390

  2. Peripheral Pain Mechanisms in Chronic Widespread Pain

    OpenAIRE

    Staud, Roland

    2011-01-01

    Clinical symptoms of chronic widespread pain (CWP) conditions including fibromyalgia (FM), include pain, stiffness, subjective weakness, and muscle fatigue. Muscle pain in CWP is usually described as fluctuating and often associated with local or generalized tenderness (hyperalgesia and/or allodynia). This tenderness related to muscle pain depends on increased peripheral and/or central nervous system responsiveness to peripheral stimuli which can be either noxious (hyperalgesia) or non-noxiou...

  3. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

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    Lo TC

    2016-09-01

    Full Text Available Tony Chung Tung Lo,1,* Stephen Tung Yeung,2,* Sujin Lee,1 Kira Skavinski,3 Solomon Liao,4 1Department of Physical Medicine and Rehabilitation, University of California Irvine, Orange, CA, 2Department of Immunology, University of Connecticut School of Medicine, Farmington, CT, 3Department of Palliative Medicine, University of California San Diego, La Jolla, 4Department of Palliative Medicine, University of California Irvine, Orange, CA, USA *These authors contributed equally to this work Objective: Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report: A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion: Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of

  4. Reduction of central neuropathic pain with ketamine infusion in a patient with Ehlers–Danlos syndrome: a case report

    Science.gov (United States)

    Lo, Tony Chung Tung; Yeung, Stephen Tung; Lee, Sujin; Skavinski, Kira; Liao, Solomon

    2016-01-01

    Objective Ehlers–Danlos syndrome frequently causes acute and chronic pain because of joint subluxations and dislocations secondary to hypermobility. Current treatments for pain related to Ehlers–Danlos syndrome and central pain syndrome are inadequate. This case report discusses the therapeutic use of ketamine intravenous infusion as an alternative. Case report A 27-year-old Caucasian female with a history of Ehlers–Danlos syndrome and spinal cord ischemic myelopathy resulting in central pain syndrome, presented with severe generalized body pain refractory to multiple pharmacological interventions. After a 7-day course of ketamine intravenous infusion under controlled generalized sedation in the intensive care unit, the patient reported a dramatic reduction in pain levels from 7–8 out of 10 to 0–3 out of 10 on a numeric rating scale and had a significant functional improvement. The patient tolerated a reduction in her pain medication regimen, which originally included opioids, gabapentin, pregabalin, tricyclic antidepressants, and nonsteroidal anti-inflammatory drugs. Conclusion Ketamine infusion treatment has been used in various pain syndromes, including central neuropathic pain, ischemic pain, and regional pain syndrome. Reports have suggested that ketamine modulates pain by the regression of N-methyl-D-aspartate receptor to a resting state. As such, propagation of nociceptive signal to brain is interrupted allowing for the restoration of physiological balance between pain inhibition and facilitation. The present report shows that this treatment option can be used in patients with refractory central pain syndrome in the setting of spinal cord myelopathy secondary to Ehlers–Danlos syndrome. In addition, as seen in this case, this protocol can potentially decrease the chronic use of pain medication, such as opioids.

  5. Prevalence of neuropathic features of back pain in clinical populations: implications for the diagnostic triage paradigm.

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    Hush, Julia M; Marcuzzi, Anna

    2012-07-01

    SUMMARY Contemporary clinical assessment of back pain is based on the diagnostic triage paradigm. The most common diagnostic classification is nonspecific back pain, considered to be of nociceptive etiology. A small proportion are diagnosed with radicular pain, of neuropathic origin. In this study we review the body of literature on the prevalence of neuropathic features of back pain, revealing that the point prevalence is 17% in primary care, 34% in mixed clinical settings and 53% in tertiary care. There is evidence that neuropathic features of back pain are not restricted to typical clinical radicular pain phenotypes and may be under-recognized, particularly in primary care. The consequence of this is that in the clinic, diagnostic triage may erroneously classify patients with nonspecific back pain or radicular pain. A promising alternative is the development of mechanism-based pain phenotyping in patients with back pain. Timely identification of contributory pain mechanisms may enable greater opportunity to select appropriate therapeutic targets and improve patient outcomes.

  6. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: The first step in pain neuroscience education.

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    Wijma, Amarins J; van Wilgen, C Paul; Meeus, Mira; Nijs, Jo

    2016-07-01

    Pain neuroscience education (PNE) is increasingly used as part of a physical therapy treatment in patients with chronic pain. A thorough clinical biopsychosocial assessment is recommended prior to PNE to allow proper explanation of the neurophysiology of pain and the biopsychosocial interactions in an interactive and patient-centered manner. However, without clear guidelines, clinicians are left wondering how a biopsychosocial assessment should be administered. Therefore, we provided a practical guide, based on scientific research and clinical experience, for the biopsychosocial assessment of patients with chronic pain in physiotherapy practice. The purpose of this article is to describe the use of the Pain - Somatic factors - Cognitive factors - Emotional factors - Behavioral factors - Social factors - Motivation - model (PSCEBSM-model) during the intake, as well as a pain analysis sheet. This model attempts to clearly establish what the dominant pain mechanism is (predominant nociceptive, neuropathic, or non-neuropathic central sensitization pain), as well as to assess the provoking and perpetuating biopsychosocial factors in patients with chronic pain. Using this approach allows the clinician to specifically classify patients and tailor the plan of care, including PNE, to individual patients. PMID:27351769

  7. Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: The first step in pain neuroscience education.

    Science.gov (United States)

    Wijma, Amarins J; van Wilgen, C Paul; Meeus, Mira; Nijs, Jo

    2016-07-01

    Pain neuroscience education (PNE) is increasingly used as part of a physical therapy treatment in patients with chronic pain. A thorough clinical biopsychosocial assessment is recommended prior to PNE to allow proper explanation of the neurophysiology of pain and the biopsychosocial interactions in an interactive and patient-centered manner. However, without clear guidelines, clinicians are left wondering how a biopsychosocial assessment should be administered. Therefore, we provided a practical guide, based on scientific research and clinical experience, for the biopsychosocial assessment of patients with chronic pain in physiotherapy practice. The purpose of this article is to describe the use of the Pain - Somatic factors - Cognitive factors - Emotional factors - Behavioral factors - Social factors - Motivation - model (PSCEBSM-model) during the intake, as well as a pain analysis sheet. This model attempts to clearly establish what the dominant pain mechanism is (predominant nociceptive, neuropathic, or non-neuropathic central sensitization pain), as well as to assess the provoking and perpetuating biopsychosocial factors in patients with chronic pain. Using this approach allows the clinician to specifically classify patients and tailor the plan of care, including PNE, to individual patients.

  8. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy.

    Science.gov (United States)

    O'Connor, Alec B

    2009-01-01

    A number of different diseases or injuries can damage the central or peripheral nervous system and produce neuropathic pain (NP), which seems to be more difficult to treat than many other types of chronic pain. As a group, patients with NP have greater medical co-morbidity burden than age- and sex-adjusted controls, which makes determining the humanistic and economic burden attributable to NP challenging. Health-related quality of life (HR-QOL) is substantially impaired among patients with NP. Patients describe pain-related interference in multiple HR-QOL and functional domains, as well as reduced ability to work and reduced mobility due to their pain. In addition, the spouses of NP patients have been shown to experience adverse social consequences related to NP. In randomized controlled trials, several medications have been shown to improve various measures of HR-QOL. Changes in HR-QOL appear to be tightly linked to pain relief, but not to the development of adverse effects. However, in cross-sectional studies, many patients continue to have moderate or severe pain and markedly impaired HR-QOL, despite taking medications prescribed for NP. The quality of NP treatment appears to be poor, with few patients receiving recommended medications in efficacious dosages. The substantial costs to society of NP derive from direct medical costs, loss of the ability to work, loss of caregivers' ability to work and possibly greater need for institutionalization or other living assistance. No single study has measured all of these costs to society for chronic NP. The cost effectiveness of various interventions for the treatment or prevention of different types of NP has been assessed in several different studies. The most-studied diseases are post-herpetic neuralgia and painful diabetic neuropathy, for which tricyclic antidepressants (both amitriptyline and desipramine) have been found to be either cost effective or dominant relative to other strategies. Increasing the use of

  9. Maintaining efficacy in the treatment of diabetic peripheral neuropathic pain: role of duloxetine

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    Lindsay Zilliox

    2010-01-01

    Full Text Available Lindsay Zilliox1, James W Russell1,21Department of Neurology, Neuromuscular Division, The University of Maryland School of Medicine, 2VA Maryland Health Care System, Baltimore, MD, USAIntroduction: Neuropathy is one of the most frequent complications of diabetes. Of all the symptoms associated with diabetic neuropathy, pain has the largest impact on sleep and quality of life. In the past few years further medications have been added to the available therapies for neuropathic pain. One of these medications, duloxetine hydrochloride (duloxetine, is a balanced and potent selective serotonin and norepinephrine reuptake inhibitor.Methods: Medline was searched from January 2005 to September 2009 using the key words duloxetine and peripheral neuropathy for clinical trials limited to human research published in English and duloxetine and pharmacology in the nervous system.Results: Duloxetine has been shown to effectively reduce diabetic peripheral neuropathic pain compared to placebo at doses of 60 mg/day and 120 mg/day with minimal to moderate side effects. This effect is seen with minimal effects on glycemic control and without any clinically relevant effects on lipid control, or cardiovascular parameters. In addition, its efficacy and tolerability is comparable to other medications commonly used in the management of neuropathic pain. Furthermore, duloxetine performs favorably both in terms of quality of life and in cost utility analyses.Discussion and conclusion: This article reviewed the issues related to management of diabetic peripheral neuropathic pain, the pharmacology and rationale for use of duloxetine, efficacy studies, and the safety and tolerability of treatment with duloxetine. Duloxetine is an acceptable initial or alternative treatment for patients with diabetic neuropathic pain.Keywords: duloxetine, diabetic neuropathy, neuropathic pain

  10. Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief

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    Tozaki-Saitoh Hidetoshi

    2009-04-01

    Full Text Available Abstract Background Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain. Results Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 μM and 1.87 μM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine. Conclusion These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part

  11. Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection

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    Keppel Hesselink JM

    2013-09-01

    Full Text Available J M Keppel Hesselink Faculty of Medicine, University Witten/Herdecke, Germany Abstract: Chronic idiopathic axonal polyneuropathy is a frequent diagnosis in patients suffering from idiopathic polyneuropathy and neuropathic pain. No guidelines exist on how to treat these patients. To date, there are no results available from randomized clinical trials, and mostly classical neuropathic analgesics are prescribed, such as amitriptyline and gabapentine. However, the usefulness of these drugs is limited, as many patients remain in pain despite treatment, or suffer debilitating side effects. Palmitoylethanolamide (PEA is a new analgesic compound, tested in more than 4,000 patients in various clinical trials in a variety of patients suffering from various neuropathic pain states. It is available in Europe and the USA as a food supplement under the brand name PeaPure, and it is available for medical purposes in Italy and Spain under brand names Normast and Pelvilen. We present a case series of seven patients with an electrophysiological confirmed diagnosis of chronic idiopathic axonal polyneuropathy, suffering from neuropathic pains, mostly refractory to previous analgesics. In all these patients, PEA reduced pain significantly, without side effects. PEA can be administered in addition to other analgesics, without negative drug–drug interactions, or can be used as a stand-alone analgesic. Due to a favorable ratio between efficacy and safety, PEA should be considered more often as a treatment for neuropathic pain. Keywords: CIAP, polyneuropathy, treatment, neuropathic

  12. HIV-Associated Distal Neuropathic Pain is Associated with Smaller Total Cerebral Cortical Gray Matter

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    Keltner, John R.; Fennema-Notestine, Christine; Vaida, Florin; Wang, Dongzhe; Franklin, Donald R.; Dworkin, Robert H.; Sanders, Chelsea; McCutchan, J. Allen; Archibald, Sarah L.; Miller, David J.; Kesidis, George; Cushman, Clint; Kim, Sung Min; Abramson, Ian; Taylor, Michael J.; Theilmann, Rebecca J.; Julaton, Michelle D.; Notestine, Randy J.; Corkran, Stephanie; Cherner, Mariana; Duarte, Nichole A.; Alexander, Terry; Robinson-Papp, Jessica; Gelman, Benjamin B.; Simpson, David M.; Collier, Ann C.; Marra, Christina M.; Morgello, Susan; Brown, Greg; Grant, Igor; Atkinson, J. Hampton; Jernigan, Terry L.; Ellis, Ronald J.

    2014-01-01

    Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50% of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging (MRI) volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Antiretroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (R = −0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance. PMID:24549970

  13. Mice undergoing neuropathic pain induce anxiogenic-like effects and hypernociception in cagemates.

    Science.gov (United States)

    Baptista-de-Souza, Daniela; Nunciato, Ana C; Pereira, Barbara C; Fachinni, Gabriel; Zaniboni, Caroline R; Canto-de-Souza, Azair

    2015-10-01

    Rodents can recognize pain-related responses in conspecifics. Therefore, cohabitation with a conspecific animal with chronic pain can potentially promote a stressful situation, which can trigger behavioral changes such as anxiety and depression and alter nociceptive responses. In this study we investigated the effect of cohabitation with a mouse undergoing sciatic nerve constriction (neuropathic pain model). The cagemates were evaluated for nociception (writhing test), anxiety (elevated plus-maze and open field tests), depression (forced swim, tail suspension, and sucrose preference tests), and corticosterone levels. Male Swiss mice were housed in pairs for 14 days, and then divided into three groups: cagemate nerve constriction, in which one animal of each pair was subjected to constriction of the sciatic nerve; cagemate sham, in which one animal from each pair was subjected to the same surgery but without constriction; and control, in which animals were not subjected to any surgical procedure. After 14 days, the cagemates were evaluated using behavioral tests. Social interaction with a conspecific undergoing constriction of the sciatic nerve induced hypernociception and increased anxiety-related responses, whereas in depression tests inconclusive responses and no changes in corticosterone levels were found. In conclusion, cohabitation with suffering conspecifics induces changes in nociceptive responses, as well as in affective responses including anxiety. PMID:26258589

  14. Neuropathic itch.

    Science.gov (United States)

    Oaklander, Anne Louise

    2011-06-01

    Chronic itch can be caused by dysfunctions of itch-sensing neurons that produce sensory hallucinations of pruritogenic stimuli. The cellular and molecular mechanisms are still unknown. All neurological disease categories have been implicated, and neurological causes should be considered for patients with otherwise-unexplained itch. The same neurological illnesses that cause neuropathic pain can also or instead cause itch. These include shingles (particularly of the head or neck), small-fiber polyneuropathies, radiculopathies (eg, notalgia paresthetica and brachioradial pruritis), and diverse lesions of the trigeminal nerve, root, and central tracts. Central nervous system lesions affecting sensory pathways, including strokes, multiple sclerosis, and cavernous hemangiomas, can cause central itch. Neuropathic itch is a potent trigger of reflex and volitional scratching although this provides only fleeting relief. Rare patients whose lesion causes sensory loss as well as neuropathic itch can scratch deeply enough to cause painless self-injury. The most common location is on the face (trigeminal trophic syndrome). Treating neuropathic itch is difficult; antihistamines, corticosteroids, and most pain medications are largely ineffective. Current treatment recommendations include local or systemic administration of inhibitors of neuronal excitability (especially local anesthetics) and barriers to reduce scratching. PMID:21767768

  15. Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

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    Xiao-Peng Mei

    2012-09-01

    Full Text Available Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

  16. Ceftriaxone, a Beta-Lactam Antibiotic, Modulates Apoptosis Pathways and Oxidative Stress in a Rat Model of Neuropathic Pain

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    Bahareh Amin

    2014-01-01

    Full Text Available Purpose. In our previous study, ceftriaxone, a beta-lactam antibiotic, elicited antinociceptive effects in the chronic constriction injury (CCI of neuropathic pain. In this study, we assessed apoptosis and oxidative stress in the spinal cord of neuropathic rats treated with ceftriaxone. Methods. 45 male Wistar rats were divided as naïve, sham, normal saline-treated CCI rats, and CCI animals treated with the effective dose of ceftriaxone. Involvement of Bax, Bcl2, and caspases 3 and 9, important contributors of programmed cell death (apoptosis, was determined using western blotting at days 3 and 7. The markers of oxidative stress including malondialdehyde (MDA and reduced glutathione (GSH were measured on days 3 and 7. Results. Increased Bax/Bcl2 ratio and cleaved active forms of caspases 3 and 9 were observed in the spinal cord of CCI rats on day 3. Ceftriaxone attenuated the increased levels of Bax and cleaved forms of caspases 3 and 9, while it increased Bcl2 levels. Bax and active forms of caspases declined by day 7. Consequently, comparison among groups showed no difference at this time. CCI enhanced MDA and decreased GSH on days 3 and 7, while ceftriaxone protected against the CCI-induced oxidative stress. Conclusion. Our results suggest that ceftriaxone, an upregulator/activator of GLT1, could concomitantly reduce oxidative stress and apoptosis and producing its new analogs lacking antimicrobial activity may represent a novel approach for neuropathic pain treatment.

  17. 78 FR 12832 - Request for Information: Public-Private Collaborations in Pain Research

    Science.gov (United States)

    2013-02-25

    ... associated pain, including phantom limb, neuropathic pain, headaches, complex regional pain syndrome, burns...-traumatic Stress Disorder, fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome, and...

  18. [Experience in treatment of patients with neuropathic facial pain using ziconotide].

    Science.gov (United States)

    Lux, E A; Rasche, D

    2011-08-01

    We report on the intrathecal use of ziconotide in three patients with idiopathic facial pain after surgery of the mouth, jaw or face and one patient with neuropathic pain after damage of the lingual nerve. The therapy was successful in three patients but one patient with idiopathic facial pain had pain relief only during the test phase of ziconotide with an external pump and not after implanting the Synchromed® pump. With intrathecal morphine therapy this patient achieved good pain relief. We recommend that patients with neuropathic facial pain should be treated with ziconotide after implementation of guideline-based therapy. In the test phase the ziconotide dose should be increased by 0.6 µg/day per week after an initial dose of 0.6-1.2 µg/day to avoid side-effects. PMID:21818721

  19. Neuropathic osteoarthropathy: iconographic essay

    International Nuclear Information System (INIS)

    Neuropathic osteoarthropathy is characterized by chronic, destructive and non-infectious bone and joint disease developing in patients with some level of loss of proprioception or pain insensitivity. Currently, diabetes mellitus is the most frequent cause of neuropathic osteoarthropathy. The classic appearance on X-rays is bone fragmentation, osteophytosis, joint effusion and joint instability, with preserved bone density. Although conventional X-rays is the most frequently used imaging modality for the evaluation of neuropathic osteoarthropathy and the role of the imaging methods are reviewed as a pictorial essay. (author)

  20. Chronic pain in Rehabilitation Medicine

    NARCIS (Netherlands)

    Geertzen, J.H.B.; van Wilgen, C.P.; Schrier, E.; Dijkstra, P.U.

    2006-01-01

    In this paper the chronicity of pain in non-specific pain syndromes is discussed. Experts in the study of pain with several professional backgrounds in rehabilitation are the authors of this paper. Clinical experience and literature form the basis of the paper. Non-specific low back pain and Complex

  1. [Pathophysiology of neuropathic pain: review of experimental models and proposed mechanisms].

    Science.gov (United States)

    Garcia-Larrea, Luis; Magnin, Michel

    2008-02-01

    Neuropathic pain can be conceptualized as the result of an "aberrant learning" process, associated with maladaptive plasticity of the nervous system. A number of modifications of the peripheral nervous system have been described in animal models of neuropathic pain, but their relation with different symptoms in humans is far from fully understood. We note in particular ectopic discharges in damaged myelinated fibers, abnormal activity in undamaged fibers, overexpression of calcium channels increasing the release of excitatory neurotransmitters, and sympathetic sprouting towards the spinal ganglia. Spinal mechanisms involve central sensitization, kindling and potentiation phenomena. Underlying these phenomena may be connectivity changes--still controversial--of non-nociceptive terminals and variations in the sensitivity of postsynaptic receptors. Also contributing to these pathophysiologic modifications are attenuation of spinal inhibition by selective neuronal loss and the development of inflammatory phenomena, including cytokine secretion by macrophages and glial cells. Changes in the dorsal horn modify the activity of projections towards the brainstem and increase spinal hyperactivity still further by feedback loops. These effects are delayed, suggesting that maintenance of spinal sensitization requires the involvement of mechanisms of descending facilitation involving the brainstem. These phenomena induce changes in the activity of thalamocortical networks, which develop autonomous processes that maintain the pain. The cortical representation of body areas change after nervous lesions, and these changes may correlate with the emergence of pain. Neuropathic allodynia and hyperalgesia are supported by cortical modifications that experimental models reproduce very incompletely. Experimental allodynia and neuropathic allodynia share the activation of the cortical pain matrix as well as the bilateralization of insular activity. However, although experimental

  2. Continuous neuropathic pain secondary to endoscopic procedures: report of two cases and review of the literature.

    Science.gov (United States)

    Kalladka, Mythili; Nasri-Heir, Cibele; Eliav, Eli; Ananthan, Sowmya; Viswanath, Archana; Heir, Gary

    2016-08-01

    Neuropathic pain encompasses a spectrum of conditions that can arise from a lesion or dysfunction of the central or the peripheral nervous system, and it may develop at variable intervals after nerve injury or inflammation. Nerve injuries arising from surgical procedures commonly occur secondary to the surgical trauma, and in rare instances they are a complication of intubation during general anesthesia or endoscopic procedures. A series of 2 cases of bilateral glossopharyngeal neuropathic pain subsequent to endoscopic procedures is presented with a review of the literature concerning the mechanisms of development of neuropathic pain after these procedures. The purpose of these case reports is to make dentists aware of the occurrence, the mechanisms of nerve injuries, and the treatment of neuropathic pain after endoscopic procedures. In the first case, the patient had relief of pain with a combination therapy of clonazepam 1.0 mg in divided doses twice daily and gabapentin 300 mg in divided doses 3 times daily. In the second case, the patient had significant relief of pain with a monotherapy of gabapentin 1200 mg in divided doses 3 times daily. PMID:27422430

  3. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

    OpenAIRE

    Woojin Kim; Min Joon Kim; Donghyun Go; Byung-Il Min; Heung Sik Na; Sun Kwang Kim

    2016-01-01

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechan...

  4. The effect of Normast (PEA) in neuropathic pain in spinal cord injury

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede;

    2015-01-01

    and psychological functioning in patients with spinal cord injury. Methods: A randomized, double-blind, placebo-controlled parallel multicenter study. We have included 66 patients with neuropathic pain due to spinal cord injury. Questionnaires regarding neuropathic pain, spasticity, insomnia, anxiety and depression......% incomplete tetraplegia, 29% complete paraplegia and 27% incomplete paraplegia. Average age at inclusion is 55.3 (±9.5) years and average time since injury is 8.8 (±8.9) years. Causes of injury are 29% transport, 26% fall, 25% unspecified or unknown, 16% other traumatic causes and 4% sports injuries. No major...

  5. Respective pharmacological features of neuropathic-like pain evoked by intrathecal BDNF versus sciatic nerve ligation in rats.

    Science.gov (United States)

    M'Dahoma, Saïd; Barthélemy, Sandrine; Tromilin, Claire; Jeanson, Tiffany; Viguier, Florent; Michot, Benoit; Pezet, Sophie; Hamon, Michel; Bourgoin, Sylvie

    2015-11-01

    Numerous reported data support the idea that Brain Derived Neurotrophic Factor (BDNF) is critically involved in both depression and comorbid pain. The possible direct effect of BDNF on pain mechanisms was assessed here and compared with behavioral/neurobiological features of neuropathic pain caused by chronic constriction injury to the sciatic nerve (CCI-SN). Sprague-Dawley male rats were either injected intrathecally with BDNF (3.0 ng i.t.) or subjected to unilateral CCI-SN. Their respective responses to anti-hyperalgesic drugs were assessed using the Randall-Selitto test and both immunohistochemical and RT-qPCR approaches were used to investigate molecular/cellular mechanisms underlying hyperalgesia in both models. Long lasting hyperalgesia and allodynia were induced by i.t. BDNF in intact healthy rats like those found after CCI-SN. Acute treatment with the BDNF-TrkB receptor antagonist cyclotraxin B completely prevented i.t. BDNF-induced hyperalgesia and partially reversed this symptom in both BDNF-pretreated and CCI-SN lesioned rats. Acute administration of the anticonvulsant pregabalin, the NMDA receptor antagonist ketamine, the opioid analgesics morphine and tapentadol or the antidepressant agomelatine also transiently reversed hyperalgesia in both i.t. BDNF injected- and CCI-SN lesioned-rats. Marked induction of microglia activation markers (OX42, Iba1, P-p38), proinflammatory cytokine IL-6, NMDA receptor subunit NR2B and BDNF was found in spinal cord and/or dorsal root ganglia of CCI-SN rats. A long lasting spinal BDNF overexpression was also observed in BDNF i.t. rats, indicating an autocrine self-induction, with downstream long lasting TrkB-mediated neuropathic-like pain. Accordingly, TrkB blockade appeared as a relevant approach to alleviate not only i.t. BDNF- but also nerve lesion-evoked neuropathic pain. PMID:26343858

  6. The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

    Science.gov (United States)

    Klauke, A-L; Racz, I; Pradier, B; Markert, A; Zimmer, A M; Gertsch, J; Zimmer, A

    2014-04-01

    The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressed cannabinoid receptor 2 (CB₂). It is found in relatively high concentrations in many spices and food plants. A number of studies have shown that CB₂ is critically involved in the modulation of inflammatory and neuropathic pain responses. In this study, we have investigated the analgesic effects of BCP in animal models of inflammatory and neuropathic pain. We demonstrate that orally administered BCP reduced inflammatory (late phase) pain responses in the formalin test in a CB₂ receptor-dependent manner, while it had no effect on acute (early phase) responses. In a neuropathic pain model the chronic oral administration of BCP attenuated thermal hyperalgesia and mechanical allodynia, and reduced spinal neuroinflammation. Importantly, we found no signs of tolerance to the anti-hyperalgesic effects of BCP after prolonged treatment. Oral BCP was more effective than the subcutaneously injected synthetic CB₂ agonist JWH-133. Thus, the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

  7. Management of chronic pain in osteoporosis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Paolucci T

    2016-04-01

    Full Text Available Teresa Paolucci,* Vincenzo Maria Saraceni, Giulia Piccinini* Physical Medicine and Rehabilitation Unit, Azienda Policlinico Umberto I, Rome, Italy *These authors contributed equally to this work Abstract: Osteoporosis (OP is a pathological condition that manifests clinically as pain, fractures, and physical disability, resulting in the loss of independence and the need for long-term care. Chronic pain is a multidimensional experience with sensory, affective, and cognitive aspects. Age can affect each of these dimensions and the pain that is experienced. In OP, chronic pain appears to have sensory characteristics and properties of nociceptive and neuropathic pain. Its evaluation and treatment thus require a holistic approach that focuses on the specific characteristics of this population. Pain management must therefore include pharmacological approaches, physiotherapy interventions, educational measures, and, in rare cases, surgical treatment. Most rehabilitative treatments in the management of patients with OP do not evaluate pain or physical function, and there is no consensus on the effects of rehabilitation therapy on back pain or quality of life in women with OP. Pharmacological treatment of pain in patients with OP is usually insufficient. The management of chronic pain in patients with OP is complicated with regard to its diagnosis, the search for reversible secondary causes, the efficacy and duration of oral bisphosphonates, and the function of calcium and vitamin D. The aim of this review is to discuss the most appropriate solutions in the management of chronic pain in OP. Keywords: physical therapy, exercise, pharmacological treatment, posture and balance

  8. Chemokine CCL2 and its receptor CCR2 in the medullary dorsal horn are involved in trigeminal neuropathic pain

    Directory of Open Access Journals (Sweden)

    Zhang Zhi-Jun

    2012-07-01

    Full Text Available Abstract Background Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2-chemokine C-C motif receptor 2 (CCR2 signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. Methods The inferior alveolar nerve and mental nerve transection (IAMNT was used to induce trigeminal neuropathic pain. The expression of ATF3, CCL2, glial fibrillary acidic protein (GFAP, and CCR2 were detected by immunofluorescence histochemical staining and western blot. The cellular localization of CCL2 and CCR2 were examined by immunofluorescence double staining. The effect of a selective CCR2 antagonist, RS504393 on pain hypersensitivity was checked by behavioral testing. Results IAMNT induced persistent (>21 days heat hyperalgesia of the orofacial region and ATF3 expression in the mandibular division of the trigeminal ganglion. Meanwhile, CCL2 expression was increased in the medullary dorsal horn (MDH from 3 days to 21 days after IAMNT. The induced CCL2 was colocalized with astroglial marker GFAP, but not with neuronal marker NeuN or microglial marker OX-42. Astrocytes activation was also found in the MDH and it started at 3 days, peaked at 10 days and maintained at 21 days after IAMNT. In addition, CCR2 was upregulated by IAMNT in the ipsilateral medulla and lasted for more than 21 days. CCR2 was mainly colocalized with NeuN and few cells were colocalized with GFAP. Finally, intracisternal injection of CCR2 antagonist, RS504393 (1, 10 μg significantly attenuated IAMNT-induced heat hyperalgesia. Conclusion The data suggest that CCL2-CCR

  9. Antinociceptive effect of matrine on vincristine-induced neuropathic pain model in mice.

    Science.gov (United States)

    Linglu, Dun; Yuxiang, Li; Yaqiong, Xu; Ru, Zhou; Lin, Ma; Shaoju, Jin; Juan, Du; Tao, Sun; Jianqiang, Yu

    2014-06-01

    Chemotherapy drugs treatment causes neuropathic pain, hyperalgesia and allodynia are common components of neuropathic pain, so effectively therapeutic strategy is required. In this study, we evaluated the antinociceptive effects of matrine on vincristine-induced neuropathic pain in mice. Vincristine (100 μg/kg i.p.) was administered once per day for 7 days (day 0-6) in mice. Matrine (15, 30, 60 mg/kg, i.p.) was repeated administration in early phase (day 0-6) or late phase (day 7-13). Hyperalgesia and allodynia were evaluated by withdrawal response using von Frey filaments, plantar and cold-plate on 7, 14 and 21 day. Injection of vincristine produced mechanical hyperalgesia and cold allodynia. Matrine was found to produce a protective role in both von Frey filaments and cold-plate test. The analysis of the effect supports the hypothesis that matrine is useful in therapy of vincristine-induced neuropathic pain. In conclusion, this study demonstrates that administration of matrine is associated with antinociceptive effect on mechanical and cold stimuli in a mice model of vincristine-induced neuropathy pain.

  10. TRPA1 mediates trigeminal neuropathic pain in mice downstream of monocytes/macrophages and oxidative stress.

    Science.gov (United States)

    Trevisan, Gabriela; Benemei, Silvia; Materazzi, Serena; De Logu, Francesco; De Siena, Gaetano; Fusi, Camilla; Fortes Rossato, Mateus; Coppi, Elisabetta; Marone, Ilaria Maddalena; Ferreira, Juliano; Geppetti, Pierangelo; Nassini, Romina

    2016-05-01

    Despite intense investigation, the mechanisms of the different forms of trigeminal neuropathic pain remain substantially unidentified. The transient receptor potential ankyrin 1 channel (encoded by TRPA1) has been reported to contribute to allodynia or hyperalgesia in some neuropathic pain models, including those produced by sciatic nerve constriction. However, the role of TRPA1 and the processes that cause trigeminal pain-like behaviours from nerve insult are poorly understood. The role of TRPA1, monocytes and macrophages, and oxidative stress in pain-like behaviour evoked by the constriction of the infraorbital nerve in mice were explored. C57BL/6 and wild-type (Trpa1(+/+)) mice that underwent constriction of the infraorbital nerve exhibited prolonged (20 days) non-evoked nociceptive behaviour and mechanical, cold and chemical hypersensitivity in comparison to sham-operated mice (P pain-like behaviours (both P stress by-products (hydrogen peroxide and 4-hydroxynonenal). Attenuation of monocyte/macrophage increase by systemic treatment with an antibody against the monocyte chemoattractant chemokine (C-C motif) ligand 2 (CCL2) or the macrophage-depleting agent, clodronate (both P pain-like behaviours (all P neuropathic pain, pain-like behaviours are entirely mediated by the TRPA1 channel, targeted by increased oxidative stress by-products released from monocytes and macrophages clumping at the site of nerve injury. PMID:26984186

  11. Neuropathic pain in neuromyelitis optica affects activities of daily living and quality of life.

    Science.gov (United States)

    Zhao, Sizheng; Mutch, Kerry; Elsone, Liene; Nurmikko, Turo; Jacob, Anu

    2014-10-01

    Though pain in neuromyelitis optica (NMO) has been described in two recent reports, the proportion with true neuropathic pain (NP), its features, impact on activities of daily living (ADL) and quality of life has not been well characterised. A cross-sectional study of 50 NMO patients with transverse myelitis was performed using Douleur Neuropathique 4, Brief Pain Inventory, Extended Disability Status Scale and Short Form 36. NP was identified in 62% of patients. Pain was constant in 68% affecting most ADL. Pain was associated with significant reduction of the SF36 Mental Composite Score. The high prevalence of NP and associated disability necessitates an in-depth enquiry in patients with NMO.

  12. Pain treatment with ziconotide and baclofen in a case of spasticity associated with neuropathic pain

    Directory of Open Access Journals (Sweden)

    Danilo G. Quarta

    2009-03-01

    Full Text Available This study presents the clinical case of a patient with paraparesis, subjected for a long period of time to treatment with intrathecal baclofen and morphine to control spasticity and neuropathic pain, resulting from spinal cord injury due to road trauma. After several years of treatment the pain was not controlled with high doses of intrathecal morphine combined with transmucosal fentanyl that were given when needed. It was therefore decided to switch to intrathecal ziconotide. Starting with high levels of intrathecal morphine, the patient was referred first to weaning from morphine to a gradual titration of ziconotide doses of up to 7.4 mcg/die associated with 680 mcg/die of baclofen. A technical problem related to the infusion pump has led to the abrupt interruption of the administration of ziconotide and baclofen, which did not cause side effects, except for a poorly controlled pain. The spasticity, however, did not recur. After replacing the intrathecal pump and restarting the gradual titration of ziconotide alone, the patient has once again regained a good pain control with no recurrence to date of spasticity.

  13. Irrational drug use in neuropathic pain treatment: a two-year data analysis

    Directory of Open Access Journals (Sweden)

    Tan E

    2013-01-01

    Full Text Available Background: Neuropathic pain (NeP manifests as chronic pain and causes significant medical and economic burden for both the individual and the society. Treatment of NeP is often symptomatic and includes single or combination drug therapy. Many drugs that are not recommended in the guidelines are also widely used. Aim: The present study was aimed at determining the annual cost of NeP treatment in Turkey and to assess the amount of resource loss due to irrational drug use and its associated complications. Methods: Each item in NeP prescriptions and their relevant costs between July 2007 and June 2009 was retrospectively analyzed. Results: The number of prescriptions for NeP was 8646358 and 9650641 for the first and second years, respectively. The irrational items were 7513299 in the first year and 8360754 in the second year. The proportion of irrational treatment cost was 48.5% for the first year and 48.6% for the second year. Total cost of these prescriptions was estimated to be 47924534 Turkish Liras and 60715905 Turkish Liras for the first and second years, respectively. The estimated irrational treatment cost of NeP together with the additional burden exceeded half of the total cost. Conclusions: Further studies on health economics perspective are needed to confirm these results. Better education of healthcare professionals and better regulations in reimbursement will help to improve this problem.

  14. Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China

    Institute of Scientific and Technical Information of China (English)

    GAO Yan; CHENG Lu-lu; WEN Chong-yuan; ZHANG Shu-yu; ZHANG Qi; Durisala Desaiah; Vladimir Skljarevski; NING Guang; JIA Wei-ping; ZHOU Zhi-guang; XU Zhang-rong; LIU Zhi-min; LIU Chao; MA Jian-hua; LI Qiang

    2010-01-01

    Background Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor, has been shown to be effective in treatment of diabetic peripheral neuropathic pain and approved for the management of patients with diabetic peripheral neuropathic pain (DPNP) in the United States, European Union, and many other countries. This study assessed the efficacy and safety of duloxetine in Chinese patients with diabetic peripheral neuropathic pain.Methods This double-blind, randomized, placebo-controlled, flexible-dose study treated adult patients with diabetic peripheral neuropathic pain and baseline Brief Pain Inventory (BPI) 24-hour average pain severity ratings ≥4 with duloxetine 60 mg to 120 mg once daily or placebo for 12 weeks. Dose adjustments of duloxetine or matching placebo were based upon investigator's judgment of clinical response. Change from baseline to endpoint in BPI average pain was the primary efficacy outcome. Secondary outcome measures included BPI-severity and -Interference, Patient Global Impression of Improvement, Clinical Global Impressions of Severity, EuroQol: 5 Dimensions, Athens Insomnia Scale, and safety measures.Results Of 215 patients randomized, 88.4% and 82.1% of patients in placebo and duloxetine groups, respectively,completed the study. Mean change from baseline to endpoint in BPI average pain was not statistically different between the treatment groups (P=0.124). Duloxetinetreated patients showed significantly greater pain reduction compared with those in placebo group at weeks 1,2, and 4 (P=0.004, P=0.009, and P=0.006, respectively),but not at weeks 8 (P=0.125) and 12 (P=0.107).Duloxetine-treated patients experienced statistically significant improvement in Patient Global Impression of Improvement, Clinical Global Impression of Severity, area under the curve for pain relief, BPI-severity pain right now,and BPI-interference walking ability. Patients treated with duloxetine 120 mg once daily showed significantly greater pain reduction

  15. Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

    Science.gov (United States)

    Liu, Su; Liu, Yue-Peng; Huang, Zhi-Jiang; Zhang, Yan-Kai; Song, Angela A; Ma, Ping-Chuan; Song, Xue-Jun

    2015-12-01

    Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca-dependent signals CaMKII, Src, ERK, PKCγ, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain.

  16. PRACTICAL CHRONIC PAIN ASSESSMENT TOOLS IN CLINICAL PRACTICE.

    Science.gov (United States)

    Loncarić-Katušin, Mirjana; Milošević, Milan; Žilić, Antonio; Mišković, Petar; Majerić-Kogler, Višnja; Žunić, Josip

    2016-03-01

    The aim of the study was to show the role of tools in the evaluation of chronic pain (CP) in general practitioner (GP) everyday clinical practice. The study was done by analyzing electronic database of the first visits of 1090 CP patients referred to the Pain Clinic of the Karlovac General Hospital, Karlovac, Croatia, by their GPs. All patient records were analyzed according to the cause of CP, strongest pain a week before the examination, quality of sleep, and the Patients' Global Impression of Change scale. All statistical analyses were done using the IBM SPSS Statistics version 19.0.0.1 (www.spss.com). CP predominantly occurs in older age group. Patients with musculoskeletal pain accounted for the highest percentage (n = 316; 29%), followed by those with neuropathic pain (n = 253; 23.20%) and those with low back pain (n = 225; 20.60%). The mean pain intensity rating scale score was 8.3 ± 1.8 a week before the examination and the mean quality of sleep score was 6.8 ± 1.9. Moderate and severe sleep quality disorder was significantly present in patients over 65 years of age (p = 0.007), patients with musculoskeletal and neuropathic pain, back pain, and those having rated Patients' Global Impression of Change scale as worsening (p = 0.001). The severity of pain and poor quality of sleep are the leading causes of deterioration of the Patients' Global Impression of Change scale in patients suffering from musculoskeletal and neuropathic pain. In order to treat CP comprehensively, it is important for GPs to evaluate the outcomes of clinical treatment using tools for CP assessment. PMID:27276768

  17. Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.

    Science.gov (United States)

    Gutierrez, Tannia; Crystal, Jonathon D; Zvonok, Alexander M; Makriyannis, Alexandros; Hohmann, Andrea G

    2011-09-01

    Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. The percentage of active lever responding was similar in naive groups self-administering vehicle or (R,S)-AM1241. The CB(2) antagonist SR144528 blocked both antiallodynic effects of (R,S)-AM1241 self-medication and the percentage of active lever responding in neuropathic (but not naive) rats. Neuropathic and sham groups exhibited similar percentages of active lever responding for (R,S)-AM1241 on a fixed ratio 1 (FR1) schedule. However, neuropathic animals worked harder than shams to obtain (R,S)-AM1241 when the schedule of reinforcement was increased (to FR6). (R,S)-AM1241 self-medication on FR1, FR3, or FR6 schedules attenuated nerve injury-induced mechanical allodynia. (R,S)-AM1241 (900μg intravenously) failed to produce motor ataxia observed after administration of the mixed CB(1)/CB(2) agonist WIN55,212-2 (0.5mg/kg intravenously). Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain. PMID:21550725

  18. Effects of naringenin on allodynia and hyperalgesia in rats with chronic constriction injury-induced neuropathic pain%柚苷配基对慢性压迫性损伤引起的大鼠触摸痛及痛觉过敏的影响

    Institute of Scientific and Technical Information of China (English)

    Shyam Kaulaskar; Pravinkumar Bhutada; Anand Rahigude; Dilpesh Jain; Uday Harle

    2012-01-01

    OBJECTIVE:To study the analgesic effects of naringenin on chronic constriction injury (CCI)model of neuropathic pain.METHODS:After inducing of neuropathic pain by CCI,treatment with 25 and 50 mg/kg of naringenin and 10 mg/kg of pregabalin was given.Rats were evaluated for behavioral tests using Hargreaves apparatus for thermal hyperalgesia,pin prick test for tactile mechanical hyperalgesia and cold water-induced allodynia on days 0,3,5,7,14 and 21.At the end of study,oxidative stress parameters were measured.RESULTS:Naringenin showed ameliorating action against CCI-induced neuropathic pain in all the tested models.Also,naringenin attenuated the elevated levels of lipid peroxidation and nitric oxide,and restored the level of reduced glutathione.CONCLUSION:The results of the present investigation suggest that naringenin exhibits analgesic effect in sciatic nerve injury model.%目的:研究柚苷配基对慢性压迫性神经损伤模型的镇痛效果.方法:经慢性压迫性损伤建立神经性疼痛大鼠模型后,分别给予模型大鼠25和50 mg/kg的柚苷配基以及10 mg/kg的普加巴林.在第0、3、5、7、14和21天采用Hargreaves方法评估大鼠的行为变化,针刺实验测试触觉性机械痛觉过敏和经冷水诱发的异常性疼痛,最后测定氧化应激反应参数.结果:柚苷配基能缓解经慢性压迫性损伤诱发的神经性疼痛,减轻脂质过氧化反应,降低一氧化氮水平,恢复还原型谷胱甘肽含量.结论:柚苷配基能缓解坐骨神经损伤引起的疼痛.

  19. Dynamic long-term microstructural and ultrastructural alterations in sensory nerves of rats of paclitaxel-induced neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Wu Yuan; Li Jun; Zhou Junfei; Feng Yi

    2014-01-01

    to the chronic neuropathic pain.

  20. Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Jun-Ming ZHANG; Judith A. Strong

    2008-01-01

    Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states. It has been well-documented that, after peripheral nerve injury or inflammation, functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings, the injured or inflamed afferent fibers, the dorsal root ganglion (DRG), and the central afferent terminals in the spinal cord. Among all the changes, ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest, as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain. Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury: the injured afferent fibers (neuroma) leading to the DRG, and the DRG somata. The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain. Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation. Further, mechanisms involved in the generation of spontaneous activity are also reviewed; evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed. An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.

  1. Voltage-Gated Ion Channels in the PNS: Novel Therapies for Neuropathic Pain?

    Science.gov (United States)

    Tibbs, Gareth R; Posson, David J; Goldstein, Peter A

    2016-07-01

    Neuropathic pain arises from injury to the nervous system. Conditions associated with neuropathic pain are diverse, and lesions and/or pathological changes in the central nervous system (CNS) or peripheral nervous system (PNS) can frequently, but not always, be identified. It is difficult to treat, with patients often on multiple, different classes of medications, all with appreciable adverse side effect profiles. Consequently, there is a pressing need for the development of new medications. The development of such therapeutics is predicated on a clear understanding of the relevant molecular and cellular processes that contribute to the development, and maintenance, of the neuropathic pain state. One proposed mechanism thought to contribute to the ontogeny of neuropathic pain is altered expression, trafficking, and functioning of ion channels expressed by primary sensory neurons. Here, we will focus on three voltage-gated ion channel families, CaV, HCN, and NaV, first reviewing the preclinical data and then the human data where it exists. PMID:27233519

  2. Neuropathic pain: an updated grading system for research and clinical practice

    DEFF Research Database (Denmark)

    Finnerup, Nanna B; Haroutounian, Simon; Kamerman, Peter;

    2016-01-01

    for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014...

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

    Directory of Open Access Journals (Sweden)

    Jaggi Amteshwar

    2010-01-01

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

  4. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain.

    Science.gov (United States)

    Barnes, Michael Philip

    2006-04-01

    Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely. PMID:16553576

  5. α2δ Modulators for management of compression neuropathic pain: A review of three case series

    Directory of Open Access Journals (Sweden)

    Tariq A Tramboo

    2009-01-01

    Conclusion: These results indicate the effectiveness of a2d modulators for management of neuropathic pain secondary to compression radiculopathy. The results also suggest a possible therapeutic superiority of LYRICA over locally available generic brands of pregabalin and gabapentin. These findings need to be further examined in randomized, controlled trials.

  6. Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model Efeito analgésico preemptivo da lidocaína em modelo de dor crônica neuropática

    Directory of Open Access Journals (Sweden)

    Leonardo M. Batista

    2009-12-01

    Full Text Available Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control; group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005 and reduction in the latency to both noxious (p=0.003 and non-noxious (p=0.004 thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004 and longer latency times when compared to Group 2. Preemptive use of lidocaine 2% can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.A analgesia preemptiva inibe a progressão da dor causada por lesão cirúrgica. Para analisar o efeito da lidocaína na diminuição da dor pós-operatória, submetemos ratos Wistar a compressão cirúrgica do nervo ciático e observamos diferenças em alguns padrões de comportamento entre o grupo tratado com lidocaína pré-operatória e o grupo não-tratado com o anestésico local. O grupo 1 não foi operado (controle; o grupo 2, submetido a ligadura do nervo ciático sem lidocaína, apresentou significativo aumento do tempo de coçar-se com um pico no 14º pós-operatório (p=0.0005 e redução na latência para os estímulos térmicos nocivo (p=0.003 e não-nocivo (p=0.004; o grupo 3, operado com a droga preemptiva, demonstrou significativo decréscimo no tempo de coçar-se (p=0.004 e maiores tempos de latência quando comparados aos do grupo 2. O uso preemptivo da lidocaína 2% pode, potencialmente, reduzir a dor neuropática pós-operatória associada à compress

  7. Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization

    Science.gov (United States)

    Sant’Anna, Morena B.; Kusuda, Ricardo; Bozzo, Tiago A.; Bassi, Gabriel S.; Alves-Filho, José C.; Cunha, Fernando Q.; Ferreira, Sergio H.; Souza, Guilherme R.; Cunha, Thiago M.

    2016-01-01

    Peripheral neuropathic pain is a consequence of an injury/disease of the peripheral nerves. The mechanisms involved in its pathophysiology are not entirely understood. To better understand the mechanisms involved in the development of peripheral nerve injury-induced neuropathic pain, more experimental models are required. Here, we developed a novel peripheral neuropathic pain model in mice by using a minimally invasive surgery and medial plantar nerve ligation (MPNL). After MPNL, mechanical allodynia was established, and mice quickly recovered from the surgery without any significant motor impairment. MPNL causes an increased expression of ATF-3 in the sensory neurons. At 14 days after surgery, gabapentin was capable of reversing the mechanical allodynia, whereas anti-inflammatory drugs and opioids were ineffective. MPNL-induced neuropathic pain was mediated by glial cells activation and the production of TNF-α and IL-6 in the spinal cord. These results indicate MPNL as a reasonable animal model for the study of peripheral neuropathic pain, presenting analgesic pharmacological predictivity to clinically used drugs. The results also showed molecular phenotypic changes similar to other peripheral neuropathic pain models, with the advantage of a lack of motor impairment. These features indicate that MPNL might be more appropriate for the study of neuropathic pain than classical models. PMID:27230787

  8. Management of chronic visceral pain

    DEFF Research Database (Denmark)

    Olesen, Anne E; Farmer, Adam D; Olesen, Søren S;

    2016-01-01

    Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological......' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations...... in central pain processing....

  9. Interprofessional Education for the Dentist in Managing Acute and Chronic Pain.

    Science.gov (United States)

    Shaefer, Jeffry; Barreveld, Antje M; Arnstein, Paul; Kulich, Ronald J

    2016-10-01

    Dental education is at the intersection of affordable health care, opioid-abuse crisis, and collaborative practice benefits. Students must engage in interprofessional education (IPE) for pain management. Graduates must recognize appropriate management of acute dental pain and understand the dentist's role in interprofessional treatment of chronic disease, including management of temporomandibular disorders and orofacial neuropathic pain, chronic pain in general, and the consideration of opioids. This article reviews accreditation standards, compares these standards with recommendations from the International Association for the Study of Pain and regulatory boards, and presents examples of enhanced pain education. PMID:27671956

  10. Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin.

    Science.gov (United States)

    Stoicea, Nicoleta; Russell, Daric; Weidner, Greg; Durda, Michael; Joseph, Nicholas C; Yu, Jeffrey; Bergese, Sergio D

    2015-01-01

    Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA) analog anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

  11. Opioid-Induced Hyperalgesia in Chronic Pain Patients and the Mitigating Effects of Gabapentin

    Directory of Open Access Journals (Sweden)

    Nicoleta eStoicea

    2015-05-01

    Full Text Available Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH, wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA analogue anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

  12. Treatment of localized neuropathic pain after disk herniation with 5% lidocaine medicated plaster

    OpenAIRE

    Likar, Rudolf; Kager,Ingo; Obmann,; Pipam, Wolfgang; Sittl, Reinhard

    2012-01-01

    Rudolf Likar,1 Ingo Kager,1 Michael Obmann,1 Wolfgang Pipam,1 Reinhard Sittl21Department of Anesthesiology and Intensive Care, Klagenfurt Hospital, Klagenfurt, Austria; 2Department of Anesthesiology, Interdisciplinary Pain Center, University Hospital Erlangen, Erlangen, GermanyObjective: To assess treatment with the 5% lidocaine medicated plaster for peripheral neuropathic pain after disk herniation.Study design: Case series, single center, retrospective data.Patients and methods: Data of 23 ...

  13. Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect

    Directory of Open Access Journals (Sweden)

    Meric Ben Boujema

    2015-01-01

    Full Text Available BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR. The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.

  14. Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain

    OpenAIRE

    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 ...

  15. Effect of Ethyl Pyruvate on Paclitaxel-Induced Neuropathic Pain in Rats

    OpenAIRE

    Choi, Seong Soo; Koh, Won Uk; Nam, Jae Sik; Shin, Jin Woo; Leem, Jeong Gill; Suh, Jeong Hun

    2013-01-01

    Background Although paclitaxel is a widely used chemotherapeutic agent for the treatment of solid cancers, side effects such as neuropathic pain lead to poor compliance and discontinuation of the therapy. Ethyl pyruvate (EP) is known to have analgesic effects in several pain models and may inhibit apoptosis. The present study was designed to investigate the analgesic effects of EP on mechanical allodynia and apoptosis in dorsal root ganglion (DRG) cells after paclitaxel administration. Method...

  16. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    OpenAIRE

    Domenico Intiso; Mario Basciani; Andrea Santamato; Marta Intiso; Filomena Di Rienzo

    2015-01-01

    Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP) results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies pro...

  17. Widespread pain in chronic epicondylitis.

    Science.gov (United States)

    Pienimäki, Tuomo; Siira, Pertti; Vanharanta, Heikki

    2011-10-01

    We studied the associations of widespread pain with other pain and functional measures among patients with chronic epicondylitis. A total of 190 patients (66% females) participated in the study; with a mean age 43.7, mean duration of symptoms 48weeks, chronic lateral (n=160) and medial (n=30) epicondylitis. We analysed clinical status, grip strength and cubital pain thresholds and interviewed pain and disability, leisure time physical activity, strenuous hobby activities for arms, duration of symptoms, other systemic and upper extremity disorders, arm operations, and work ability. The location of pain was analysed using a whole-body pain drawing, categorized into three groups; the highest of which was classified as widespread pain. A total of 85 patients (45%) reported widespread pain. It was highly associated with female gender, high pain scores, decreased grip strength and pain thresholds (p<0.001 for all), with increased number of positive manual tests, low level of hobby strain for arms and physical activity, long duration of symptoms, and sick leave (p for all <0.05). It was also related to upper extremity disorders and arm surgery, but not with operated epicondylitis, other systemic diseases, workload or work ability. In addition, 39% of patients without other disease reported widespread pain. Widespread pain is common in chronic epicondylitis with and without other diseases, and is related to high pain scores, decreased function of the arm, long duration of symptoms, sick leave, and with a low level of physical activity. PMID:21565536

  18. The CanPain SCI Clinical Practice Guidelines for Rehabilitation Management of Neuropathic Pain after Spinal Cord: screening and diagnosis recommendations

    DEFF Research Database (Denmark)

    Mehta, S; Guy, S D; Bryce, T N;

    2016-01-01

    in Canada. METHODS: The CanPainSCI Working Group reviewed evidence to address clinical questions regarding screening and diagnosis of neuropathic pain after SCI. A consensus process was followed to achieve agreement on recommendations and clinical considerations. RESULTS: Twelve recommendations......, based on expert consensus, were developed for the screening and diagnosis of neuropathic pain after SCI. The recommendations address methods for assessment, documentation tools, team member accountability, frequency of screening and considerations for diagnostic investigation. Important clinical...... considerations accompany each recommendation. CONCLUSIONS: The expert Working Group developed recommendations for the screening and diagnosis of neuropathic pain after SCI that should be used to inform practice....

  19. Fighting Chronic Pain

    Science.gov (United States)

    ... leg pain from clogged arteries Stomach/Digestive: Gallstones, intestinal obstruction, diverticulitis, ulcers, severe indigestion, severe gas pain, inflammatory bowel disease, colitis Urinary/Reproductive: Kidney stones, pelvic pain, vulvodynia, ...

  20. Adult Stem Cell as New Advanced Therapy for Experimental Neuropathic Pain Treatment

    Directory of Open Access Journals (Sweden)

    Silvia Franchi

    2014-01-01

    Full Text Available Neuropathic pain (NP is a highly invalidating disease resulting as consequence of a lesion or disease affecting the somatosensory system. All the pharmacological treatments today in use give a long lasting pain relief only in a limited percentage of patients before pain reappears making NP an incurable disease. New approaches are therefore needed and research is testing stem cell usage. Several papers have been written on experimental neuropathic pain treatment using stem cells of different origin and species to treat experimental NP. The original idea was based on the capacity of stem cell to offer a totipotent cellular source for replacing injured neural cells and for delivering trophic factors to lesion site; soon the researchers agreed that the capacity of stem cells to contrast NP was not dependent upon their regenerative effect but was mostly linked to a bidirectional interaction between the stem cell and damaged microenvironment resident cells. In this paper we review the preclinical studies produced in the last years assessing the effects induced by several stem cells in different models of neuropathic pain. The overall positive results obtained on pain remission by using stem cells that are safe, of easy isolation, and which may allow an autologous transplant in patients may be encouraging for moving from bench to bedside, although there are several issues that still need to be solved.

  1. Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief

    Science.gov (United States)

    Moriconi, Alessio; Cunha, Thiago M.; Souza, Guilherme R.; Lopes, Alexandre H.; Cunha, Fernando Q.; Carneiro, Victor L.; Pinto, Larissa G.; Brandolini, Laura; Aramini, Andrea; Bizzarri, Cinzia; Bianchini, Gianluca; Beccari, Andrea R.; Fanton, Marco; Bruno, Agostino; Costantino, Gabriele; Bertini, Riccardo; Galliera, Emanuela; Locati, Massimo; Ferreira, Sérgio H.; Teixeira, Mauro M.; Allegretti, Marcello

    2014-01-01

    Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. Pharmacological therapies currently available for certain types of pain are only partially effective and may cause severe adverse side effects. The C5a anaphylatoxin acting on its cognate G protein-coupled receptor (GPCR), C5aR, is a potent pronociceptive mediator in several models of inflammatory and neuropathic pain. Although there has long been interest in the identification of C5aR inhibitors, their development has been complicated, as for many peptidomimetic drugs, mostly by poor drug-like properties. Herein, we report the de novo design of a potent and selective C5aR noncompetitive allosteric inhibitor, DF2593A, guided by the hypothesis that an allosteric site, the “minor pocket,” previously characterized in CXC chemokine receptors-1 and -2, is functionally conserved in the GPCR class. In vitro, DF2593A potently inhibited C5a-induced migration of human and rodent neutrophils. In vivo, oral administration of DF2593A effectively reduced mechanical hyperalgesia in several models of acute and chronic inflammatory and neuropathic pain, without any apparent side effects. Mechanical hyperalgesia after spared nerve injury was also reduced in C5aR−/− mice compared with WT mice. Furthermore, treatment of C5aR−/− mice with DF2593A did not produce any further antinociceptive effect compared with C5aR−/− mice treated with vehicle. The successful medicinal chemistry strategy confirms that a conserved minor pocket is amenable for the rational design of selective inhibitors and the pharmacological results support that the allosteric blockade of the C5aR represents a highly promising therapeutic approach to control chronic inflammatory and neuropathic pain. PMID:25385614

  2. How to investigate: Chronic pain.

    Science.gov (United States)

    Hague, Matthew; Shenker, Nicholas

    2014-12-01

    Chronic pain is defined as an unpleasant sensory and emotional experience persisting longer than the normal process of healing, usually longer than 3 months. About a fifth of the world's population is believed to suffer from chronic pain. In Europe, chronic pain accounts for nearly 500 m lost working days, and it costs the European economy >€34 billion (£28 billion) every year. Establishing a reliable diagnosis is the primary challenge in evaluating a patient with chronic pain. Common diagnoses not to miss include seronegative spondyloarthritides, endocrine abnormalities including severe vitamin D deficiency and polymyalgia rheumatica. Once important or treatable diagnoses have been ruled out, the history can be used as a tool to establish a therapeutic plan for shared decision-making using the biopsychosocial model. Onward referral to pain clinics can be helpful for more involved patient management, but often good outcomes are achieved with the support of primary care. PMID:26096090

  3. [Spinal cord stimulation for the management of chronic pain].

    Science.gov (United States)

    Perruchoud, Christophe; Mariotti, Nicolas

    2016-06-22

    Neuromodulation techniques modify the activity of the central or peripheral nervous system. Spinal cord stimulation is a reversible and minimally invasive treatment whose efficacy and cost effectiveness are recognized for the treatment of chronic neuropathic pain or ischemic pain. Spinal cord stimulation is not the option of last resort and should be considered among other options before prescribing long-term opioids or considering reoperation. The selection and regular follow-up of patients are crucial to the success of the therapy. PMID:27506068

  4. An Innovative and Portable Multimodal Pain Relief Device for the Management of Neuropathic Low Back Pain - a Study from Kashmir (Southeast Asia)

    Science.gov (United States)

    Lone, Baseer-ul-Rasool; Beigh, Mirza-Idrees-ul-Haq; Manzoor, Mushbiq

    2016-01-01

    We developed a portable multimodal system with seven different mechanisms of pain relief incorporated into a lumbar belt called the Comfort-N-Harmony Belt (C&H belt). Here, we describe the technical details of the system and also summarize the effects of this multimodal pain relieving technology as an adjuvant to analgesics versus analgesics alone, on the level of pain, improvement of psychological status, disability, and the quality of life in the patients with neuropathic low back pain (LBP). We tracked the volunteers who were following up at a tertiary health care center for the complaints of neuropathic LBP of minimum three months duration and were on analgesics alone with no relief in the severity of the pain. Study group A (n = 45) consisted of volunteers with LBP on C&H belt therapy, along with the usually prescribed analgesic intake, and group B (n = 45) with LBP volunteers on analgesics, plus a similar looking but plain leather belt (placebo). For pain, the VAS (Visual Analogue Scale); for anxiety and depression, the (HADS) Hospital Anxiety-Depression Scale; for disability, the RMDQ (Roland Morris Disability Questionnaire); and for quality of life, (NHP) Nottingham-Health-Profile were used before and after the study period.  There were no significant differences in demographic variables between the groups (p 0.05). However, in comparison of pre- and post-treatment scores, the pre-treatment score values of RMDQ, NHP-pain, NHP-physical activity, and NHP-social isolation were much higher in group A compared to the group B, but still these scores were, in a statistically significant manner, improved in group A compared to the group B after the study period was over (p < 0.05). Multiple pain relieving mechanisms in a portable device-based system, when used along with analgesics, are effective in relieving pain, improving function and quality of life, and help in relieving the associated anxiety and depression in patients with chronic neuropathic LBP than

  5. A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

    Directory of Open Access Journals (Sweden)

    Wu Ann

    2011-01-01

    Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

  6. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

    Directory of Open Access Journals (Sweden)

    Zlateva Gergana

    2010-11-01

    Full Text Available Abstract Background Older patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN or postherpetic neuralgia (PHN was conducted to evaluate the efficacy and safety of pregabalin in older patients. Methods Data from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs. Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction. Results 2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595 were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236, 65 to 74 years (n = 766, and ≥75 years (n = 514. Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009, except for the lowest dosage (150 mg/day in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain. Conclusions Pregabalin (150-600 mg/day significantly reduced pain in older patients (age ≥65 years with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the

  7. Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Nedergaard, S; Hansen, RR;

    2009-01-01

    Activation of spinal cord microglia and astrocytes is a common phenomenon in nerve injury pain models and is thought to exacerbate pain perception. Following a nerve injury, a transient increase in the presence of microglia takes place while the increased numbers of astrocytes stay elevated...... for an extended period of time. It has been proposed that activated microglia are crucial for the development of neuropathic pain and that they lead to activation of astrocytes which then play a role in maintaining the long term pathological pain sensation. In the present report, we examined the time course...... of spinal cord glial activation in three different murine pain models to investigate if microglial activation is a general prerequisite for astrocyte activation in pain models. We found that two different types of cancer induced pain resulted in severe spinal astrogliosis without activation of microglia...

  8. Neurovascular Unit in Chronic Pain

    Directory of Open Access Journals (Sweden)

    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.

  9. Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking and dynamic weight bearing (gait changes are not measures of neuropathic pain in mice

    Directory of Open Access Journals (Sweden)

    Schorscher-Petcu Ara

    2010-06-01

    Full Text Available Abstract Background Spontaneous (non-evoked pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury, and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait using the CatWalk® system. Results We found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury. However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations. Conclusions We conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions.

  10. Chronic pain management: nonpharmacological therapies for chronic pain.

    Science.gov (United States)

    Chang, Ku-Lang; Fillingim, Roger; Hurley, Robert W; Schmidt, Siegfried

    2015-05-01

    Nonpharmacologic therapies have become a vital part of managing chronic pain (CP). Although these can be used as stand-alone therapies, nonpharmacologic treatments often are used to augment and complement pharmacologic treatments (ie, multimodal therapy). Nonpharmacologic approaches can be classified as behavioral, cognitive, integrative, and physical therapies. Core principles in developing a treatment plan are explaining the nature of the CP condition, setting appropriate goals, and developing a comprehensive treatment approach and plan for adherence. Clinicians should become familiar with these interventions so that they can offer patients flexibility in the pain management approach. Effective noninvasive treatment modalities for CP include behavioral therapy for short-term pain relief; cognitive behavioral therapy for reducing long-term pain and disability; hypnosis as adjunctive therapy; guided imagery, diaphragmatic breathing, and muscle relaxation, especially for cancer-related pain; mindfulness-based stress reduction for patients with chronic low back pain; acupuncture for multiple pain conditions; combination manipulation, manual therapy, endurance exercise, stretching, and strengthening for chronic neck pain; animal-assisted therapy; and S-adenosyl-L-methionine for joint pain. Guidelines for use of these treatment modalities are based on expert panel recommendations in combination with data from randomized controlled trials. PMID:25970869

  11. Deep brain stimulation versus motor cortex stimulation for neuropathic pain: A minireview of the literature and proposal for future research.

    Science.gov (United States)

    Honey, C Michael; Tronnier, Volker M; Honey, Christopher R

    2016-01-01

    The treatment of neuropathic pain remains a public health concern. A growing cohort of patients is plagued by medically refractory, unrelenting severe neuropathic pain that ruins their quality of life and productivity. For this group, neurosurgery can offer two different kinds of neuromodulation that may help: deep brain simulation (DBS) and motor cortex stimulation (MCS). Unfortunately, there is no consensus on how to perform these procedures, which stimulation parameters to select, how to measure success, and which patients may benefit. This brief review highlights the literature supporting each technique and attempts to provide some comparisons and contrasts between DBS and MCS for the treatment of neuropathic pain. Finally, we highlight the current unanswered questions in the field and suggest future research strategies that may advance the care of our patients with neuropathic pain.

  12. What Is Chronic Pain?

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    Full Text Available ... the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs Resource Guide to ... pain is real. Site Map Terms & Conditions Privacy Policy Advertising Policy Language Disclaimer Endorsement Policy Development of ...

  13. What Is Chronic Pain?

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    Full Text Available ... Resources Going to the ER Glossary Surveys What We Have Learned Communication Tools Videos Pain Management Programs ... pain is different. And because it is different, we need to think about it in very different ...

  14. The CanPain SCI Clinical Practice Guideline for Rehabilitation Management of Neuropathic Pain after Spinal Cord: recommendations for model systems of care

    DEFF Research Database (Denmark)

    Guy, S D; Mehta, S; Harvey, D;

    2016-01-01

    STUDY DESIGN: Clinical practice guidelines. OBJECTIVES: The project objectives were to develop the first Canadian recommendations on a model of care for the management of at- and below-level neuropathic pain in people with spinal cord injury (SCI). SETTING: The guidelines are relevant for inpatient...... process. RESULTS: The Working Group developed five recommendations for the organization of neuropathic pain rehabilitation care in people with SCI. CONCLUSIONS: The Working Group recommendations for a model of care for at- and below-level neuropathic pain after SCI should be used to inform clinical...

  15. Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain.

    Science.gov (United States)

    Inceoglu, Bora; Bettaieb, Ahmed; Trindade da Silva, Carlos A; Lee, Kin Sing Stephen; Haj, Fawaz G; Hammock, Bruce D

    2015-07-21

    Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes. PMID:26150506

  16. Methadone: applied pharmacology and use as adjunctive treatment in chronic pain

    OpenAIRE

    Brown, R.; C. Kraus; Fleming, M.; Reddy, S.

    2004-01-01

    This article reviews the unique pharmacological properties of methadone and outlines its appropriate clinical application, with focus upon its use in the treatment of chronic pain. Although methadone is most widely known for its use in the treatment of opioid dependence, methadone also provides effective analgesia. Patients who experience inadequate pain relief or intolerable side effects with other opioids or who suffer from neuropathic pain may benefit from a transition to methadone as thei...

  17. Tumor necrosis factor-α and neuropathic pain%肿瘤坏死因子-α和神经病理性疼痛

    Institute of Scientific and Technical Information of China (English)

    郑亚国; 马正良

    2011-01-01

    Background Neuropathic pain is a chronic pain state which is usually produced by injured nervous system.Because of its complex mechanisms,there still has been in lack of efficacious drugs to manage.Objective TNF-α is an important pro-inflammatory cytokine which is released early during nerve injury and neuroinflammation. Recently,many studies show that TNF-α which is expressed by activated immune cells in both peripheral nerve and spinal cord plays a critical role in the development of neuropathic pain.Content This article makes a brief review of the role of TNF-α on neuropathic pain,providing a theory basis for anti- TNF-α therapy in alleviating neuropathic pain.Trend As the pathophysiological mechanisms of neuropathic pain are much better understood,TNF-α may be a new target for neuropathic pain therapeutics.%背景 神经病理性疼痛(Neuropatlic pain,NP)是神经系统损伤引起的一种慢性疼痛,其发病机制复杂,至今尚缺乏有效的治疗药物.目的 肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)是神经损伤和神经炎症过程早期释放的重要致炎细胞因子.近年来,许多研究显示外周及脊髓免疫细胞激活后表达的TNF-α在NP形成过程中具有重要的作用.内容 现就TNF-α在NP中的作用作一综述,为临床抗TNF-α治疗NP提供理论依据.趋向 随着对TNF-α在神经病理性疼痛中机制的深入理解,TNF-α可能成为临床上治疗NP的新靶点.

  18. Synaptic Conversion of Chloride-Dependent Synapses in Spinal Nociceptive Circuits: Roles in Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mark S. Cooper

    2011-01-01

    Full Text Available Electrophysiological conversion of chloride-dependent synapses from inhibitory to excitatory function, as a result of aberrant neuronal chloride homeostasis, is a known mechanism for the genesis of neuropathic pain. This paper examines theoretically how this type of synaptic conversion can disrupt circuit logic in spinal nociceptive circuits. First, a mathematical scaling factor is developed to represent local aberration in chloride electrochemical driving potential. Using this mathematical scaling factor, electrophysiological symbols are developed to represent the magnitude of synaptic conversion within nociceptive circuits. When inserted into a nociceptive circuit diagram, these symbols assist in understanding the generation of neuropathic pain associated with the collapse of transmembrane chloride gradients. A more generalized scaling factor is also derived to represent the interplay of chloride and bicarbonate driving potentials on the function of GABAergic and glycinergic synapses. These mathematical and symbolic representations of synaptic conversion help illustrate the critical role that anion driving potentials play in the transduction of pain. Using these representations, we discuss ramifications of glial-mediated synaptic conversion in the genesis, and treatment, of neuropathic pain.

  19. Optogenetic Silencing of Nav1.8-Positive Afferents Alleviates Inflammatory and Neuropathic Pain.

    Science.gov (United States)

    Daou, Ihab; Beaudry, Hélène; Ase, Ariel R; Wieskopf, Jeffrey S; Ribeiro-da-Silva, Alfredo; Mogil, Jeffrey S; Séguéla, Philippe

    2016-01-01

    We report a novel transgenic mouse model in which the terminals of peripheral nociceptors can be silenced optogenetically with high spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain. Inhibitory archaerhodopsin-3 (Arch) proton pumps were delivered to Nav1.8(+) primary afferents using the Nav1.8-Cre driver line. Arch expression covered both peptidergic and nonpeptidergic nociceptors and yellow light stimulation reliably blocked electrically induced action potentials in DRG neurons. Acute transdermal illumination of the hindpaws of Nav1.8-Arch(+) mice significantly reduced mechanical allodynia under inflammatory conditions, while basal mechanical sensitivity was not affected by the optical stimulation. Arch-driven hyperpolarization of nociceptive terminals was sufficient to prevent channelrhodopsin-2 (ChR2)-mediated mechanical and thermal hypersensitivity in double-transgenic Nav1.8-ChR2(+)-Arch(+) mice. Furthermore, prolonged optical silencing of peripheral afferents in anesthetized Nav1.8-Arch(+) mice led to poststimulation analgesia with a significant decrease in mechanical and thermal hypersensitivity under inflammatory and neuropathic conditions. These findings highlight the role of peripheral neuronal inputs in the onset and maintenance of pain hypersensitivity, demonstrate the plasticity of pain pathways even after sensitization has occurred, and support the involvement of Nav1.8(+) afferents in both inflammatory and neuropathic pain. Together, we present a selective analgesic approach in which genetically identified subsets of peripheral sensory fibers can be remotely and optically inhibited with high temporal resolution, overcoming the compensatory limitations of genetic ablations. PMID:27022626

  20. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.

    Science.gov (United States)

    Almeida, Cayo; DeMaman, Aline; Kusuda, Ricardo; Cadetti, Flaviane; Ravanelli, Maria Ida; Queiroz, André L; Sousa, Thais A; Zanon, Sonia; Silveira, Leonardo R; Lucas, Guilherme

    2015-03-01

    Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain. PMID:25687543

  1. Managing chronic pain in family practice.

    OpenAIRE

    Librach, S. L.

    1993-01-01

    Pain is common in family practice. In dealing with chronic pain, both the family physician and the patient often have problems in defining and in understanding the origin of chronic pain and in providing effective pain relief. This article explores a practical, holistic approach to understanding and managing chronic pain.

  2. Sustained-release pregabalin with methylcobalamin in neuropathic pain: an Indian real-life experience

    Directory of Open Access Journals (Sweden)

    Dongre YU

    2013-05-01

    Full Text Available Yasmin U Dongre, Onkar C Swami Unichem Laboratories Ltd, Unichem Bhavan, Mumbai, India Introduction: Neuropathic pain is intense in nature and difficult to manage. Thus, the primary goal is maximum relief from pain. The aim of this study was to assess the efficacy and safety of a fixed-dose combination of sustained-release pregabalin and methylcobalamin in reducing neuropathic pain in Indian patients, in the real-life situation. Methods: This was a multicenter, prospective, open-labeled, single-arm, observational, 14-day study. Patients received fixed dose combination of 75 or 150 mg sustained-release pregabalin combined with 1500 mcg immediate release methylcobalamin, depending on the clinical requirement. Data was collected for pain reduction and other positive and negative symptoms associated with neuropathy, including hyperesthesia, paresthesia, numbness/tingling, burning sensation, muscle weakness, sleep disturbances, and impairment of movement. Pain intensity was measured on a ten-point visual analog scale (VAS (0 represented "no pain," and 10 represented "worst pain ever". The safety of the drug was also evaluated throughout the study duration. Data was analyzed using appropriate statistical methods. Results: The overall reduction in mean VAS score over 14 days was 72.3%. The reduction in mean VAS score was significant as early as the first week. Both positive and negative symptoms of peripheral neuropathy were significantly improved in >50% patients within the 2 weeks. Giddiness (4.7%, followed by sedation (3.6%, dizziness (2.9%, drowsiness (2.3%, and nausea (2.3% were the most commonly observed adverse effects. The overall efficacy and tolerability was rated as good to excellent by >95% of the investigators and patients. Conclusion: Fixed dose combination of sustained-release pregabalin and methylcobalamin significantly reduced neuropathic pain, with significant improvement in both the positive and negative symptoms associated with

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

    Directory of Open Access Journals (Sweden)

    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

  4. Botulinum Toxin Type A for the Treatment of Neuropathic Pain in Neuro-Rehabilitation

    Directory of Open Access Journals (Sweden)

    Domenico Intiso

    2015-06-01

    Full Text Available Pain is a natural protective mechanism and has a warning function signaling imminent or actual tissue damage. Neuropathic pain (NP results from a dysfunction and derangement in the transmission and signal processing along the nervous system and it is a recognized disease in itself. The prevalence of NP is estimated to be between 6.9% and 10% in the general population. This condition can complicate the recovery from stroke, multiple sclerosis, spinal cord lesions, and several neuropathies promoting persistent disability and poor quality of life. Subjects suffering from NP describe it as burning, itching, lancing, and numbness, but hyperalgesia and allodynia represent the most bothersome symptoms. The management of NP is a clinical challenge and several non-pharmacological and pharmacological interventions have been proposed with variable benefits. Botulinum toxin (BTX as an adjunct to other interventions can be a useful therapeutic tool for the treatment of disabled people. Although BTX-A is predominantly used to reduce spasticity in a neuro-rehabilitation setting, it has been used in several painful conditions including disorders characterized by NP. The underlying pharmacological mechanisms that operate in reducing pain are still unclear and include blocking nociceptor transduction, the reduction of neurogenic inflammation by inhibiting neural substances and neurotransmitters, and the prevention of peripheral and central sensitization. Some neurological disorders requiring rehabilitative intervention can show neuropathic pain resistant to common analgesic treatment. This paper addresses the effect of BTX-A in treating NP that complicates frequent disorders of the central and peripheral nervous system such as spinal cord injury, post-stroke shoulder pain, and painful diabetic neuropathy, which are commonly managed in a rehabilitation setting. Furthermore, BTX-A has an effect in relief pain that may characterize less common neurological disorders

  5. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

    Directory of Open Access Journals (Sweden)

    Jeongsoo Han

    2015-01-01

    Full Text Available The insular cortex (IC is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ, has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ, and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.

  6. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain.

    Science.gov (United States)

    Marinelli, Sara; Nazio, Francesca; Tinari, Antonella; Ciarlo, Laura; D'Amelio, Marcello; Pieroni, Luisa; Vacca, Valentina; Urbani, Andrea; Cecconi, Francesco; Malorni, Walter; Pavone, Flaminia

    2014-01-01

    Axonal degeneration in peripheral nerves after injury is accompanied by myelin degradation initiated by Schwann cells (SCs). These cells activate autophagy, a ubiquitous cytoprotective process essential for degradation and recycling of cellular constituents. Concomitantly to nerve insult and axonal degeneration, neuropathic pain (NeP) arises. The role of SC autophagy in the mechanisms underlying NeP is still unknown. In this study, we examined the role of the autophagy during the early phase of Wallerian degeneration in NeP induction and chronification by using a murine model of peripheral nerve lesion (chronic constriction injury). We demonstrate that the autophagy inducer rapamycin, administered in the first week after nerve damage, induces long-lasting analgesic and antiinflammatory effects, facilitates nerve regeneration, and prevents pain chronification. Conversely, when autophagy is altered, by means of autophagic inhibitor 3-methyladenine administration or as occurs in activating molecule in Beclin-1-regulated autophagy transgenic mice (Ambra1(+/gt)), NeP is dramatically enhanced and prolonged. Immunohistochemical and ultrastructural evaluations show that rapamycin is able to increase autophagic flux in SCs, to accelerate myelin compaction, and to reduce inflammatory and immune reaction. Proteomic analysis combined with bioinformatic analysis suggests that a redox-sensitive mechanism could be responsible for SC autophagy activation. These data suggest that a deficiency of autophagic activity in SCs can be an early event in the origin of NeP chronification and that autophagy modulation may represent a powerful pharmacological approach to prevent the onset and chronification of NeP in the clinical setting.

  7. Characterization of a neuropathic pain model: sciatic cryoneurolysis in the rat.

    Science.gov (United States)

    DeLeo, J A; Coombs, D W; Willenbring, S; Colburn, R W; Fromm, C; Wagner, R; Twitchell, B B

    1994-01-01

    Cryoanalgesia, the technique of freezing peripheral nerves, is used clinically for the treatment of postoperative and chronic pain. Paradoxically, this same technique produces characteristics in a rat model suggestive of neuropathic pain. We have developed a peripheral neuropathy model by freezing the proximal sciatic nerve (sciatic cryoneurolysis, SCN) using a cryoprobe cooled to -60 degrees C in a 30/5/30 sec freeze-thaw-freeze sequence. Each freeze cycle produced a transient ice ball on the surface of the nerve. These studies provide behavioral evidence that SCN is a valid mononeuropathy animal model. All animals demonstrate some degree of autotomy following SCN. The average onset of autotomy occurs 4 days postoperatively and peaks in severity and incidence at 14 days. By examining the latency of responses to a noxious heat stimulus, we have shown there is no direct relationship between an hypoesthetic paw and autotomy, i.e., autotomy did not occur immediately after the freeze lesion when the limb was dysfunctional. Rather, autotomy peaked when sensation was returning to the affected limb. The transient time course of certain behaviors including hypoesthesia and possible return of limb sensation, autotomy, touch-evoked allodynia, foot edema and the presence of spontaneous nociceptive behaviors demonstrate a multiple phase nociceptive process. The temporary nature of these nociceptive behaviors is in sharp contrast to the prolonged bilateral mechanical allodynia evident when these behaviors subside. The surgical anesthetics used during the SCN procedure are shown to variably alter or suppress autotomy following SCN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8159445

  8. Pregabalin for Pain Treatment in Chronic Pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Søren Schou; Bowense, S; Wilder-Smith, Oliver;

    2011-01-01

    Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution...

  9. Chronic pain: the burden of disease and treatment innovations.

    Science.gov (United States)

    Monti, S; Caporali, R

    2015-01-01

    Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Efficacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients' long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profile, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic field, particularly in the treatment of osteoarthritis and low back pain. PMID:26492961

  10. Chronic pain: the burden of disease and treatment innovations

    Directory of Open Access Journals (Sweden)

    S. Monti

    2015-10-01

    Full Text Available Musculoskeletal conditions are the most frequent cause of chronic pain and affect around 1 in 5 adults in Europe. When chronic pain occurs, it becomes disease itself, with substantial clinical, social and economic impact. Effi cacy and tolerability problems are encountered with all therapeutic strategies available to treat musculoskeletal pain. This often limits effective analgesia and patients’ long term compliance, with the result that chronic pain is persistently underestimated and undertreated. Tapentadol is a novel, centrally acting analgesic that has been recently commercialized for the treatment of chronic pain. This new molecule, by combining two distinct mechanisms of action, μ-opioid receptor agonism (MOR and noradrenaline reuptake inhibition (NRI, introduces a new pharmacological class called MOR-NRI. Several studies demonstrated promising results in the management of both nociceptive and neuropathic pain and good tolerability profi le, particularly concerning side effects, compared to traditional opioids. This novel analgesic represents a possible therapeutic option also in the rheumatologic fi eld, particularly in the treatment of osteoarthritis and low back pain.

  11. A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Tsodikov, Alexander; Millman, Jeanna; Bentley, Heather; Gouaux, Ben; Fishman, Scott

    2016-01-01

    The Food and Drug Administration (FDA), Substance Abuse and Mental Health Services Administration (SAMHSA), and the National Institute for Drug Abuse (NIDA) report that no sound scientific studies support the medicinal use of cannabis. Despite this lack of scientific validation, many patients routinely use “medical marijuana,” and in many cases this use is for pain related to nerve injury. We conducted a double-blinded, placebo-controlled, crossover study evaluating the analgesic efficacy of smoking cannabis for neuropathic pain. Thirty-eight patients with central and peripheral neuropathic pain underwent a standardized procedure for smoking either high-dose (7%), low-dose (3.5%), or placebo cannabis. In addition to the primary outcome of pain intensity, secondary outcome measures included evoked pain using heat-pain threshold, sensitivity to light touch, psychoactive side effects, and neuropsychological performance. A mixed linear model demonstrated an analgesic response to smoking cannabis. No effect on evoked pain was seen. Psychoactive effects were minimal and well-tolerated, with some acute cognitive effects, particularly with memory, at higher doses. PMID:18403272

  12. Direct and indirect pharmacological modulation of CCL2/CCR2 pathway results in attenuation of neuropathic pain - In vivo and in vitro evidence.

    Science.gov (United States)

    Piotrowska, Anna; Kwiatkowski, Klaudia; Rojewska, Ewelina; Slusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-08-15

    The repeated administration of microglial inhibitor (minocycline) and CCR2 antagonist (RS504393) attenuated the neuropathic pain symptoms in rats following chronic constriction injury of the sciatic nerve, which was associated with decreased spinal microglia activation and the protein level of CCL2 and CCR2. Furthermore, in microglia primary cell cultures minocycline downregulated both CCL2 and CCR2 protein levels after lipopolysaccharide-stimulation. Additionally, in astroglia primary cell cultures minocycline decreased the expression of CCL2, but not CCR2. Our results provide new evidence that modulation of CCL2/CCR2 pathway by microglial inhibitor as well as CCR2 antagonist is effective for neuropathic pain development in rats. PMID:27397071

  13. Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

    Directory of Open Access Journals (Sweden)

    Dallel Radhouane

    2010-02-01

    Full Text Available Abstract Background Chikungunya virus (CHIKV is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC in a pain syndrome is a major step towards pain control. Methods We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL. Results The mean intensity of pain on the visual-analogical scale (VAS was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65% of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0. However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ(15.5 ± 5.2 vs 11.6 ± 5.2; p Conclusions There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.

  14. Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation.

    Science.gov (United States)

    Padi, Satyanarayana S V; Shi, Xiang Q; Zhao, Yuan Q; Ruff, Michael R; Baichoo, Noel; Pert, Candace B; Zhang, Ji

    2012-01-01

    Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA, a HIV gp120-derived CCR5 entry inhibitor, has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We report here that as a stabilized analog of DAPTA, the short peptide RAP-103 exhibits potent antagonism for both CCR2 (half maximal inhibitory concentration [IC50] 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. Oral administration of RAP-103 (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rats. Administered from days 8 to 12, RAP-103 (0.2-1 mg/kg) reverses already established hypersensitivity. RAP-103 relieves behavioral hypersensitivity, probably through either or both CCR2 and CCR5 blockade, because by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain. Moreover, RAP-103 is able to reduce spinal microglial activation and monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain. Our findings suggest that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone, and that dual CCR2/CCR5 antagonist RAP-103 has the potential for broad clinical use in neuropathic pain treatment.

  15. Improving the translation of analgesic drugs to the clinic: animal models of neuropathic pain

    OpenAIRE

    Percie du Sert, N; Rice, A. S. C.

    2014-01-01

    Neuropathic pain remains an area of considerable unmet clinical need. Research based on preclinical animal models has failed to deliver truly novel treatment options, questioning the predictive value of these models. This review addresses the shortcomings of rodent in vivo models commonly used in the field and highlights approaches which could increase their predictivity, including more clinically relevant assays, outcome measures and animal characteristics. The methodological quality of anim...

  16. Effects of Melatonin and Vitamin E on Peripheral Neuropathic Pain in Streptozotocin-Induced Diabetic Rats

    OpenAIRE

    Reza Heidari; Samad Zare; Farrin Babaei-Balderlou; Farah Farrokhi

    2010-01-01

    Objective(s)Previous studies have indicated that diabetes mellitus might be accompanied by neuropathic pain. Oxidative stress is implicated as a final common pathway in development of diabetic neuropathy. Pharmacological interventions targeted at inhibiting free radical production have shown beneficial effects in diabetic neuropathy. The aim of this study was to investigate and compare the possible analgesic effects of melatonin and vitamin E in diabetic rats.Materials and MethodsThis study w...

  17. The Christchurch Earthquake: Crush Injury, Neuropathic Pain, and Posttraumatic Stress Disorder

    OpenAIRE

    Frances Cammack; Shipton, Edward A.

    2013-01-01

    On February 22, 2011, an earthquake of magnitude 6.3 struck Christchurch, New Zealand. The peak ground acceleration, a measure of the shaking or intensity of an earthquake, was one of the highest ever recorded worldwide. One hundred and eighty-five people lost their lives; many others were injured. Two cases both involving young women are presented; they sustained crush injuries to limbs after being trapped by falling debris and went on to develop severe neuropathic pain. This report examines...

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

    OpenAIRE

    Jaggi Amteshwar; Kaur Gurpreet; Singh Nirmal

    2010-01-01

    Abstract The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p.) for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion test...

  19. A Mangifera indica L. Extract Could Be Used to Treat Neuropathic Pain and Implication of Mangiferin

    OpenAIRE

    María del C. Rabí; Fe Bosch; Gabino Garrido; Rene Delgado; Bárbara B. Garrido-Suárez

    2010-01-01

    It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α -induced IκB...

  20. T-type calcium channels in neuropathic pain.

    Science.gov (United States)

    Bourinet, Emmanuel; Francois, Amaury; Laffray, Sophie

    2016-02-01

    Pain is a quite frequent complaint accompanying numerous pathologies. Among these pathological cases, numerous neuropathies are retrieved with identified etiologies (chemotherapies, diabetes, surgeries…) and also more diffuse syndromes such as fibromyalgia. More broadly, pain is one of the first consequences of most inherited diseases. Despite its importance for the quality of life, current pain management is limited to drugs that are either old or with a limited efficacy or that possess a bad risk benefit ratio. As no new pharmacological concept has led to new analgesics in the last decades, the discovery of new medications is needed, and to this aim, the identification of new druggable targets in pain transmission is a first step. Therefore, studies of ion channels in pain pathways are extremely active. This is particularly true with ion channels in peripheral sensory neurons in dorsal root ganglia known how to express unique sets of these channels. Moreover, both spinal and supraspinal levels are clearly important in pain modulation. Among these ion channels, we and others revealed the important role of low voltage-gated calcium channels in cellular excitability in different steps of the pain pathways. These channels, by being activated nearby resting membrane potential, have biophysical characteristics suited to facilitate action potential generation and rhythmicity. In this review, we will present the current knowledge on the role of these channels in the perception and modulation of pain. PMID:26785151

  1. Antinociceptive effects of hydroalcoholic extract from Euterpe oleracea Mart. (Açaí) in a rodent model of acute and neuropathic pain

    OpenAIRE

    Sudo, Roberto T; Neto, Miguel L.; Monteiro, Carlos E.S.; Amaral, Rachel V.; Resende, Ângela C.; Souza, Pergentino J. C.; Zapata-Sudo, Gisele; de Moura, Roberto S

    2015-01-01

    Background Plants rich in flavonoids, such as açaí (Euterpe oleraceae Mart.), can induce antinociception in experimental animals. Here, we tested an extract obtained from the stones of açaí fruits (açaí stone extract, ASE), a native plant from the Amazon region of Brazil, in models of acute/inflammatory and chronic pain. Methods Antinociceptive effects of ASE were evaluated in the hot plate, formalin, acetic acid writhing, carrageenan, and neuropathic pain models, as well as in thermal hypera...

  2. A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects.

    Science.gov (United States)

    Ignatowska-Jankowska, Bogna M; Baillie, Gemma L; Kinsey, Steven; Crowe, Molly; Ghosh, Sudeshna; Owens, Robert A; Damaj, Imad M; Poklis, Justin; Wiley, Jenny L; Zanda, Matteo; Zanato, Chiara; Greig, Iain R; Lichtman, Aron H; Ross, Ruth A

    2015-12-01

    The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects. Here we describe the development of the novel synthetic CB1 PAM, 6-methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011), which augments the in vitro and in vivo pharmacological actions of the CB1 orthosteric agonists CP55,940 and N-arachidonoylethanolamine (AEA). ZCZ011 potentiated binding of [(3)H]CP55,940 to the CB1 receptor as well as enhancing AEA-stimulated [(35)S]GTPγS binding in mouse brain membranes and β-arrestin recruitment and ERK phosphorylation in hCB1 cells. In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.

  3. Eligibility audits for the randomized neuropathic bone pain trial (TROG 96.05)

    International Nuclear Information System (INIS)

    In February 1996 the Trans-Tasman Radiation Oncology Group (TROG) initiated a two-arm, multicentre, prospective randomized trial on radiotherapy for neuropathic pain due to bone metastases (TROG 96.05). This trial compares the response to a single 8-Gy fraction with 20 Gy in five fractions. The accrual target is 270 patients. In order to evaluate compliance with eligibility criteria after approximately 1 year of accrual, an independent audit of the first 42 randomized patients was commissioned. This found that only one of these patients did not have genuine neuropathic pain, but that this patient and seven others (19%) had infringements of other eligibility/exclusion criteria for the trial. Accordingly it was decided to continue the full audit up to 90 patients. This detected no further patients without genuine neuropathic pain, and found only one other eligibility infringement (1/48; 2%). It is concluded that this quality assurance (QA) measure undertaken early in the trial led to significantly improved clinician awareness of, and compliance with, eligibility/exclusion criteria. It also enabled an accurate comparison of outcome data for all randomized versus all eligible patients at the time of the preplanned first interim analysis at 90 patients. In view of the excellent compliance demonstrated in the second audit, a one-in-five sampling is proposed for future audits from centres that have already accrued at least five consecutive eligible patients. This is consistent with TROG QA guidelines now operational. Copyright (2000) Blackwell Science Pty Ltd

  4. The Contributing Role of CD14 in Toll-Like Receptor 4 Dependent Neuropathic Pain

    Science.gov (United States)

    Cao, Ling; Tanga, Flobert Y; DeLeo, Joyce A.

    2009-01-01

    We have previously demonstrated that central nervous system (CNS) toll-like receptor 4 (TLR4) plays a key role in the development of behavioral hypersensitivity in a rodent model of neuropathic pain, spinal nerve L5 transection (L5Tx). TLR4 is a well-known receptor for lipopolysaccharide (LPS) in innate immune responses. In the current study, we further investigated the role of CD14, an accessory molecule in the LPS-TLR4 signaling pathway, in the development of L5Tx-induced neuropathic pain. CD14 knockout (KO) mice displayed significantly decreased behavioral sensitivity (mechanical allodynia and thermal hyperalgesia) as early as day 1 post-L5Tx, indicating a nociceptive role of CD14. By flow cytometric analyses, we observed significantly elevated microglial surface CD14 expression in the ipsilateral lumbar spinal cord 3 days post-L5Tx, as well as remarkable increases in microglial size (via forward scatter (FSC)) and granularity (via side scatter (SSC)). Further, intrathecal injection of soluble CD14 induced significantly greater mechanical hypersensitivity in wild type (C3H/HeN) mice compared to TLR4-deficient (C3H/HeJ) mice. Together, these data demonstrate that CD14 plays a contributing role in TLR4-dependent nerve injury-induced neuropathic pain. PMID:18976692

  5. Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Smith TP

    2014-08-01

    Full Text Available Terika P Smith,1 Tami Haymond,1 Sherika N Smith,1 Sarah M Sweitzer1,2 1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA; 2Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA Abstract: Many people worldwide suffer from pain and a portion of these sufferers are diagnosed with a chronic pain condition. The management of chronic pain continues to be a challenge, and despite taking prescribed medication for pain, patients continue to have pain of moderate severity. Current pain therapies are often inadequate, with side effects that limit medication adherence. There is a need to identify novel therapeutic targets for the management of chronic pain. One potential candidate for the treatment of chronic pain is therapies aimed at modulating the vasoactive peptide endothelin-1. In addition to vasoactive properties, endothelin-1 has been implicated in pain transmission in both humans and animal models of nociception. Endothelin-1 directly activates nociceptors and potentiates the effect of other algogens, including capsaicin, formalin, and arachidonic acid. In addition, endothelin-1 has been shown to be involved in inflammatory pain, cancer pain, neuropathic pain, diabetic neuropathy, and pain associated with sickle cell disease. Therefore, endothelin-1 may prove a novel therapeutic target for the relief of many types of chronic pain. Keywords: endothelin-1, acute pain, chronic pain, endothelin receptor antagonists

  6. Endocannabinoid regulation of spinal nociceptive processing in a model of neuropathic pain.

    Science.gov (United States)

    Sagar, Devi Rani; Jhaveri, Maulik D; Richardson, Denise; Gray, Roy A; de Lago, Eva; Fernández-Ruiz, Javier; Barrett, David A; Kendall, David A; Chapman, Victoria

    2010-04-01

    Models of neuropathic pain are associated with elevated spinal levels of endocannabinoids (ECs) and altered expression of cannabinoid receptors on primary sensory afferents and post-synaptic cells in the spinal cord. We investigated the impact of these changes on the spinal processing of sensory inputs in a model of neuropathic pain. Extracellular single-unit recordings of spinal neurones were made in anaesthetized neuropathic and sham-operated rats. The effects of spinal administration of the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) and the cannabinoid receptor type 2 (CB(2)) receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicycloheptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) on mechanically-evoked responses of spinal neurones were determined. The effects of spinal administration of (5Z,8Z11Z,14Z)-N-(3-furanylmethyl)-5,8,11,14-eicosatetraenamide (UCM707), which binds to CB(2) receptors and alters transport of ECs, on evoked responses of spinal neurones and spinal levels of ECs were also determined. The cannabinoid CB(1) receptor antagonist AM251, but not the CB(2) receptor antagonist, significantly facilitated 10-g-evoked responses of spinal neurones in neuropathic, but not sham-operated, rats. Spinal administration of UCM707 did not alter spinal levels of ECs but did significantly inhibit mechanically-evoked responses of neurones in neuropathic, but not sham-operated, rats. Pharmacological studies indicated that the selective inhibitory effects of spinal UCM707 in neuropathic rats were mediated by activation of spinal CB(2) receptors, as well as a contribution from transient receptor potential vanilloid 1 (TRPV1) channels. This work demonstrates that changes in the EC receptor system in the spinal cord of neuropathic rats influence the processing of sensory inputs, in particular low-weight inputs that drive allodynia

  7. Efficacy of ultrasound-stellate ganglion block in breast cancer with postoperative neuropathic pain

    Directory of Open Access Journals (Sweden)

    LIU Cheng-jun

    2013-10-01

    Full Text Available Objective To compare the efficacy of ultrasound-stellate ganglion block (US-SGB with that of blind SGB (B-SGB in the management of breast cancer patients with postoperative neuropathic pain (NP. Methods Forty-eight breast cancer patients with postoperative neuropathic pain were randomly assigned to either US-SGB group (N = 24 or B-SGB group (N = 24. The mean age of US-SGB and B-SGB groups were (51.35 ± 5.63 and (49.54 ± 4.77 years, respectively. Two blockade procedures with 8-day interval were performed on the affected side. Visual Analogue Scale (VAS was assessed before treatment, and in the 4th and 8th week after treatment. Results In both groups, VAS scores were significantly decreased after 4 and 8 weeks. The VAS score in US-SGB group was decreased from 5.44 ± 1.52 before treatment to 2.68 ± 1.33 at 4th week and to 1.32 ± 0.85 at 8th week after treatment, while in B-SGB group decreased from 5.36 ± 1.21 before treatment to 3.31 ± 1.27 at 4th week and to 2.09 ± 1.02 at 8th week after treatment. The alleviation of pain in US-SGB group was more significant than that in B-SGB group (4th week: t = 2.251, P = 0.038; 8th week: t = 1.971, P = 0.029. Conclusion Both US-SGB and B-SGB techniques were effective in relieving pain in breast cancer patients with neuropathic pain. However, with postoperative favorable clinical efficacy, US-SGB was better in pain relief in comparison with B-SGB.

  8. Pain management in chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Cathia Gachago; Peter V Draganov

    2008-01-01

    Abdominal pain is a major clinical problem in patients with chronic pancreatitis.The cause of pain is usually multifactorial with a complex interplay of factors contributing to a varying degree to the pain in an individual patient and,therefore,a rigid standardized approach for pain control tends to lead to suboptimal results.Pain management usually proceeds in a stepwise approach beginning with general lifestyle recommendations,low fat diet,alcohol and smoking cessation are encouraged.Analgesics alone are needed in almost all patients.Maneuvers aimed at suppression of pancreatic secretion are routinely tried.Patients with ongoing symptoms may be candidates for more invasive options such as endoscopic therapy,and resective or drainage surgery.The role of pain modifying agents (antidepressants,gabapentin,peregabalin),celiac plexus block,antioxidants,octreotide and total pancreatectomy with islet cell auto transplantation remains to be determined.

  9. Fibromyalgia and Chronic Pain Syndromes

    Science.gov (United States)

    Choy, Ernest; Clauw, Daniel J.; Goldenberg, Don L.; Harris, Richard E.; Helfenstein, Milton; Jensen, Troels Staehelin; Noguchi, Koichi; Silverman, Stuart L.; Ushida, Takahiro; Wang, Guochun

    2016-01-01

    This manuscript, developed by a group of chronic pain researchers and clinicians from around the world, aims to address the state of knowledge about fibromyalgia (FM) and identify ongoing challenges in the field of FM and other chronic pain syndromes that may be characterized by pain centralization/amplification/hypersensitivity. There have been many exciting developments in research studies of the pathophysiology and treatment of FM and related syndromes that have the potential to improve the recognition and management of patients with FM and other conditions with FM-like pain. However, much of the new information has not reached all clinicians, especially primary care clinicians, who have the greatest potential to use this new knowledge to positively impact their patients’ lives. Furthermore, there are persistent misconceptions about FM and a lack of consensus regarding the diagnosis and treatment of FM. This paper presents a framework for future global efforts to improve the understanding and treatment of FM and other associated chronic pain syndromes, disseminate research findings, identify ways to enhance advocacy for these patients, and improve global efforts to collaborate and reach consensus about key issues related to FM and chronic pain in general. PMID:27022674

  10. What Is Chronic Pain?

    Medline Plus

    Full Text Available ... but we may be looking in the wrong time. And what I mean by that is that ... pain problem which exists for some period of time can actually change the nervous system so that ...

  11. Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation?

    Science.gov (United States)

    Fiore, Nathan T; Austin, Paul J

    2016-08-01

    Neuro-immune interactions contribute to the pathogenesis of neuropathic pain due to peripheral nerve injury. A large body of preclinical evidence supports the idea that the immune system acts to modulate the sensory symptoms of neuropathy at both peripheral and central nervous system sites. The potential involvement of neuro-immune interactions in the highly debilitating affective disturbances of neuropathic pain, such as depression, anhedonia, impaired cognition and reduced motivation has received little attention. This is surprising given the widely accepted view that sickness behaviour, depression, cognitive impairment and other neuropsychiatric conditions can arise from inflammatory mechanisms. Moreover, there is a set of well-described immune-to-brain transmission mechanisms that explain how peripheral inflammation can lead to supraspinal neuroinflammation. In the last 5years increasing evidence has emerged that peripheral nerve injury induces supraspinal changes in cytokine or chemokine expression and alters glial cell activity. In this systematic review, based on strong preclinical evidence, we advance the argument that the emergence of affective disturbances in neuropathic pain states are contingent on pro-inflammatory mediators in the interconnected hippocampal-medial prefrontal circuitry that subserve affective behaviours. We explore how dysregulation of inflammatory mediators in these networks may result in affective disturbances through a wide variety of neuromodulatory mechanisms. There are also promising results from clinical trials showing that anti-inflammatory agents have efficacy in the treatment of a variety of neuropsychiatric conditions including depression and appear suited to sub-groups of patients with elevated pro-inflammatory profiles. Thus, although further research is required, aggressively targeting supraspinal pro-inflammatory mediators at critical time-points in appropriate clinical populations is likely to be a novel avenue to treat

  12. The Central Analgesic Mechanism of YM-58483 in Attenuating Neuropathic Pain in Rats.

    Science.gov (United States)

    Qi, Zeyou; Wang, Yaping; Zhou, Haocheng; Liang, Na; Yang, Lin; Liu, Lei; Zhang, Wei

    2016-10-01

    Calcium channel antagonists are commonly used to treat neuropathic pain. Their analgesic effects rely on inhibiting long-term potentiation, and neurotransmitters release in the spinal cord. Store-operated Ca(2+)channels (SOCCs) are highly Ca(2+)-selective cation channels broadly expressed in non-excitable cells and some excitable cells. Recent studies have shown that the potent inhibitor of SOCCs, YM-58483, has analgesic effects on neuropathic pain, but its mechanism is unclear. This experiment performed on spinal nerve ligation (SNL)-induced neuropathic pain model in rats tries to explore the mechanism, whereby YM-58483 attenuates neuropathic pain. The left L5 was ligated to produce the SNL neuropathic pain model in male Sprague-Dawley rats. The withdrawal threshold of rats was measured by the up-down method and Hargreaves' method before and after intrathecal administration of YM-58483 and vehicle. The SOCCs in the spinal dorsal horn were located by immunofluorescence. The expression of phosphorylated ERK and phosphorylated CREB, CD11b, and GFAP proteins in spinal level was tested by Western blot, while the release of proinflammatory cytokines (IL-1β, TNF-α, PGE2) was measured by enzyme-linked immunosorbent assay (ELISA). Intrathecal YM-58483 at the concentration of 300 μM (1.5 nmol) and 1000 μM (10 nmol) produced a significant central analgesic effect on the SNL rats, compared with control + vehicle (n = 7, P  0.05). YM-58483 also inhibited the release of spinal cord IL-1β, TNF-α, and PGE2, compared with control + vehicle (n = 5, #P < 0.001). The analgesic mechanism of YM-58483 may be via inhibiting central ERK/CREB signaling in the neurons and decreasing central IL-1β, TNF-α, and PGE2 release to reduce neuronal excitability in the spinal dorsal horn of the SNL rats. PMID:26514127

  13. Chronic pain disorders in HIV primary care: clinical characteristics and association with healthcare utilization.

    Science.gov (United States)

    Jiao, Jocelyn M; So, Eric; Jebakumar, Jebakaran; George, Mary Catherine; Simpson, David M; Robinson-Papp, Jessica

    2016-04-01

    Chronic pain is common in HIV, but incompletely characterized, including its underlying etiologies, its effect on healthcare utilization, and the characteristics of affected patients in the HIV primary care setting. These data are needed to design and justify appropriate clinic-based pain management services. Using a clinical data warehouse, we analyzed one year of data from 638 patients receiving standard-of-care antiretroviral therapy in a large primary care HIV clinic, located in the Harlem neighborhood of New York City. We found that 40% of patients carried one or more chronic pain diagnoses. The most common diagnoses were degenerative musculoskeletal disorders (eg, degenerative spinal disease and osteoarthritis), followed by neuropathic pain and headache disorders. Many patients (16%) had multiple chronic pain diagnoses. Women, older patients, and patients with greater burdens of medical illness, and psychiatric and substance use comorbidities were disproportionately represented among those with chronic pain diagnoses. Controlling for overall health status, HIV patients with chronic pain had greater healthcare utilization including emergency department visits and radiology procedures. In summary, our study demonstrates the high prevalence of chronic pain disorders in the primary care HIV clinic. Colocated interventions for chronic pain in this setting should not only focus on musculoskeletal pain but also account for complex multifaceted pain syndromes, and address the unique biopsychosocial features of this population. Furthermore, because chronic pain is prevalent in HIV and associated with increased healthcare utilization, developing clinic-based pain management programs could be cost-effective.

  14. Mitogen activated protein kinase phosphatase-1 prevents the development of tactile sensitivity in a rodent model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ndong Christian

    2012-04-01

    Full Text Available Abstract Background Neuropathic pain due to nerve injury is one of the most difficult types of pain to treat. Following peripheral nerve injury, neuronal and glial plastic changes contribute to central sensitization and perpetuation of mechanical hypersensitivity in rodents. The mitogen activated protein kinase (MAPK family is pivotal in this spinal cord plasticity. MAPK phosphatases (MKPs limit inflammatory processes by dephosphorylating MAPKs. For example, MKP-1 preferentially dephosphorylates p-p38. Since spinal p-p38 is pivotal for the development of chronic hypersensitivity in rodent models of pain, and p-p38 inhibitors have shown clinical potential in acute and chronic pain patients, we hypothesize that induction of spinal MKP-1 will prevent the development of peripheral nerve-injury-induced hypersensitivity and p-p38 overexpression. Results We cloned rat spinal cord MKP-1 and optimize MKP-1 cDNA in vitro using transfections to BV-2 cells. We observed that in vitro overexpression of MKP-1 blocked lipopolysaccharide-induced phosphorylation of p38 (and other MAPKs as well as release of pro-algesic effectors (i.e., cytokines, chemokines, nitric oxide. Using this cDNA MKP-1 and a non-viral, in vivo nanoparticle transfection approach, we found that spinal cord overexpression of MKP-1 prevented development of peripheral nerve-injury-induced tactile hypersensitivity and reduced pro-inflammatory cytokines and chemokines and the phosphorylated form of p38. Conclusions Our results indicate that MKP-1, the natural regulator of p-p38, mediates resolution of the spinal cord pro-inflammatory milieu induced by peripheral nerve injury, resulting in prevention of chronic mechanical hypersensitivity. We propose that MKP-1 is a potential therapeutic target for pain treatment or prevention.

  15. Electroacupuncture improves neuropathic pain Adenosine,adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously

    Institute of Scientific and Technical Information of China (English)

    Wen Ren; Wenzhan Tu; Songhe Jiang; Ruidong Cheng; Yaping Du

    2012-01-01

    Applying a stimulating current to acupoints through acupuncture needles-known as electroacupuncture-has the potential to produce analgesic effects in human subjects and experimental animals.When acupuncture was applied in a rat model,adenosine 5'-triphosphate disodium in the extracellular space was broken down into adenosine,which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process.Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture.The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves.In neuropathic pain,there is upregulation of P2X purinoceptor 3(P2X3)receptor expression in dorsal root ganglion neurons.Conversely,the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated.The pathways upon which electroacupuncture appear to act are interwoven with pain pathways,and electroacupuncture stimuli converge with impulses originating from painful areas.Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.

  16. Role of capsaicin-sensitive C-fiber afferents in neuropathic pain-induced synaptic potentiation in the nociceptive amygdala

    Directory of Open Access Journals (Sweden)

    Nakao Ayano

    2012-07-01

    Full Text Available Abstract Background Neurons in the capsular part of the central nucleus of the amygdala (CeC, a region also called "nociceptive amygdala," receive nociceptive information from the dorsal horn via afferent pathways relayed from the lateral parabrachial nucleus (LPB. As the central amygdala is known to be involved in the acquisition and expression of emotion, this pathway is thought to play central roles in the generation of affective responses to nociceptive inputs. Excitatory synaptic transmission between afferents arising from the LPB and these CeC neurons is potentiated in arthritic, visceral, neuropathic, inflammatory and muscle pain models. In neuropathic pain models following spinal nerve ligation (SNL, in which we previously showed a robust LPB-CeC potentiation, the principal behavioral symptom is tactile allodynia triggered by non-C-fiber low-threshold mechanoreceptor afferents. Conversely, recent anatomical studies have revealed that most of the spinal neurons projecting to the LPB receive C-fiber afferent inputs. Here, we examined the hypothesis that these C-fiber-mediated inputs are necessary for the full establishment of robust synaptic potentiation of LPB-CeC transmission in the rats with neuropathic pain. Results Postnatal capsaicin treatment, which has been shown to denervate the C-fibers expressing transient receptor potential vanilloid type-1 (TRPV1 channels, completely abolished eye-wiping responses to capsaicin eye instillation in rats, but this treatment did not affect mechanical allodynia in the nerve-ligated animals. However, the postnatal capsaicin treatment prevented LPB-CeC synaptic potentiation after SNL, unlike in the vehicle-treated rats, primarily due to the decreased incidence of potentiated transmission by elimination of TRPV1-expressing C-fiber afferents. Conclusions C-fiber-mediated afferents in the nerve-ligated animals may be a required facilitator of the establishment of nerve injury-evoked synaptic

  17. Ganglioside GM3 synthase depletion reverses neuropathic pain and small fiber neuropathy in diet-induced diabetic mice

    Science.gov (United States)

    Jayaraj, Nirupa D; Wilson, Heather M; Ren, Dongjun; Flood, Kelsey; Wang, Xiao-Qi; Shum, Andrew; Miller, Richard J; Paller, Amy S

    2016-01-01

    Background Small fiber neuropathy is a well-recognized complication of type 2 diabetes and has been shown to be responsible for both neuropathic pain and impaired wound healing. In previous studies, we have demonstrated that ganglioside GM3 depletion by knockdown of GM3 synthase fully reverses impaired wound healing in diabetic mice. However, the role of GM3 in neuropathic pain and small fiber neuropathy in diabetes is unknown. Purpose Determine whether GM3 depletion is able to reverse neuropathic pain and small fibers neuropathy and the mechanism of the reversal. Results We demonstrate that GM3 synthase knockout and the resultant GM3 depletion rescues the denervation in mouse footpad skin and fully reverses the neuropathic pain in diet-induced obese diabetic mice. In cultured dorsal root ganglia from diet-induced diabetic mice, GM3 depletion protects against increased intracellular calcium influx in vitro. Conclusions These studies establish ganglioside GM3 as a new candidate responsible for neuropathic pain and small fiber neuropathy in diabetes. Moreover, these observations indicate that systemic or topically applied interventions aimed at depleting GM3 may improve both the painful neuropathy and the wound healing impairment in diabetes by protecting against nerve end terminal degeneration, providing a disease-modifying approach to this common, currently intractable medical issue. PMID:27590073

  18. Effect of lycopene on the expression of pain-related molecules in spinal cord of model rats with neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Dong-Hua Peng

    2016-01-01

    Objective:To analyze the effect of lycopene on the expression of pain-related molecules in spinal cord of model rats with neuropathic pain.Methods:A total of 30 healthy female SD rats were collected to establish neuropathic pain models according to the literatures, including 10 in sham operation group, 10 in model control group and 10 in model treatment group. Rats were executed to obtain L2-L6 segment of spinal cord, and then serum levels of pain-related indicators as well as gene and protein expression in it were detected.Results:Serum IL-17, HMGB-1, Aβ, Tau and C3 levels of sham operation group were lower than those of model control group and model treatment group while CGRP level was higher than that of model control group and model treatment group, and serum IL-17, HMGB-1, Aβ, Tau and C3 levels of model treatment group were lower than those of model control group while CGRP level was higher than that of model control group; ERK, CREB, BDNF, NMDA, AMPA and c-fos mRNA expression levels of sham operation group were lower than those of model control group and model treatment group, and ERK, CREB, BDNF, NMDA, AMPA and c-fos mRNA expression levels of model treatment group were lower than those of model control group; TRPV1, NF-κB, NOS, GFAP, ERK and CREB protein expression levels of sham operation group were lower than those of model control group and model treatment group while Reg expression level was higher than that of model control group and model treatment group, and TRPV1, NF-κB, NOS, GFAP, ERK and CREB protein expression levels of model treatment group were lower than those of model control group while Reg expression level was higher than that of model control group.Conclusion: Lycopene can effectively decrease the expression of pain-promoting genes in model rats with neuropathic pain, and is expected to become new treatment means of neuropathic pain in the future.

  19. Short-Term Efficacy of Ultramicronized Palmitoylethanolamide in Peripheral Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Dario Cocito

    2014-01-01

    Full Text Available Introduction. This study evaluates the efficacy of palmitoylethanolamide ultramicronized (PEA-um as an add-on treatment in patients with diabetic or traumatic neuropathic pain (NP. Methods. 30 patients with chronic NP were assessed with Visual Analogue Scale (VAS, NP Symptom Inventory (NPSI, and Health Questionnaire Five Dimensions (EQ-5D, both at baseline and after 10 and 40 days of treatment with 1200 mg/die of PEA-um. All other therapies were maintained stable during the follow-up period. Results. VAS mean score significantly improved within the first 10 days, ranging from 8.20 ± 1.53 to 6.40 ± 1.83 (P<0.002, with a further decrease to 5.80 ± 2.04 (P<0.001 after 40 days of PEA-um administration. Moreover, NPSI total score improved from 5.2 ± 1.5 to 3.8 ± 2.1 (P: 0.025 and EQ-5D ranged from −0.30 ± 0.65 to 0.5 ± 0.34 (P<0.001 between T0 and T2. Conclusions. This study reports the prospective short-term efficacy data of oral PEA-um in patients with diabetic or traumatic NP. A significant improvement was observed both in VAS and NPSI scores and in quality of life scales after 40 days of treatment, although some limitations should be considered, including the short followup and the open-label study design.

  20. Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain.

    Science.gov (United States)

    Cocito, Dario; Peci, Erdita; Ciaramitaro, Palma; Merola, Aristide; Lopiano, Leonardo

    2014-01-01

    Introduction. This study evaluates the efficacy of palmitoylethanolamide ultramicronized (PEA-um) as an add-on treatment in patients with diabetic or traumatic neuropathic pain (NP). Methods. 30 patients with chronic NP were assessed with Visual Analogue Scale (VAS), NP Symptom Inventory (NPSI), and Health Questionnaire Five Dimensions (EQ-5D), both at baseline and after 10 and 40 days of treatment with 1200 mg/die of PEA-um. All other therapies were maintained stable during the follow-up period. Results. VAS mean score significantly improved within the first 10 days, ranging from 8.20 ± 1.53 to 6.40 ± 1.83 (P < 0.002), with a further decrease to 5.80 ± 2.04 (P < 0.001) after 40 days of PEA-um administration. Moreover, NPSI total score improved from 5.2 ± 1.5 to 3.8 ± 2.1 (P: 0.025) and EQ-5D ranged from -0.30 ± 0.65 to 0.5 ± 0.34 (P < 0.001) between T0 and T2. Conclusions. This study reports the prospective short-term efficacy data of oral PEA-um in patients with diabetic or traumatic NP. A significant improvement was observed both in VAS and NPSI scores and in quality of life scales after 40 days of treatment, although some limitations should be considered, including the short followup and the open-label study design. PMID:24967102

  1. Microglial Signaling in Chronic Pain with a Special Focus on Caspase 6, p38 MAP Kinase, and Sex Dependence.

    Science.gov (United States)

    Berta, T; Qadri, Y J; Chen, G; Ji, R R

    2016-09-01

    Microglia are the resident immune cells in the spinal cord and brain. Mounting evidence suggests that activation of microglia plays an important role in the pathogenesis of chronic pain, including chronic orofacial pain. In particular, microglia contribute to the transition from acute pain to chronic pain, as inhibition of microglial signaling reduces pathologic pain after inflammation, nerve injury, and cancer but not baseline pain. As compared with inflammation, nerve injury induces much more robust morphologic activation of microglia, termed microgliosis, as shown by increased expression of microglial markers, such as CD11b and IBA1. However, microglial signaling inhibitors effectively reduce inflammatory pain and neuropathic pain, arguing against the importance of morphologic activation of microglia in chronic pain sensitization. Importantly, microglia enhance pain states via secretion of proinflammatory and pronociceptive mediators, such as tumor necrosis factor α, interleukins 1β and 18, and brain-derived growth factor. Mechanistically, these mediators have been shown to enhance excitatory synaptic transmission and suppress inhibitory synaptic transmission in the pain circuits. While early studies suggested a predominant role of microglia in the induction of chronic pain, further studies have supported a role of microglia in the maintenance of chronic pain. Intriguingly, recent studies show male-dominant microglial signaling in some neuropathic pain and inflammatory pain states, although both sexes show identical morphologic activation of microglia after nerve injury. In this critical review, we provide evidence to show that caspase 6-a secreted protease that is expressed in primary afferent axonal terminals surrounding microglia-is a robust activator of microglia and induces profound release of tumor necrosis factor α from microglia via activation of p38 MAP kinase. The authors also show that microglial caspase 6/p38 signaling is male dominant in some

  2. Vascular endothelial growth factor-expressing neural stem cell for the treatment of neuropathic pain.

    Science.gov (United States)

    Lee, Hye-Lan; Oh, Jinsoo; Yun, Yeomin; Lee, Hye Yeong; You, Youngsang; Che, Lihua; Lee, Minhyung; Kim, Keung Nyun; Ha, Yoon

    2015-05-01

    Previously, we determined that vascular endothelial growth factor (VEGF) improves the survival of neural stem cells (NSCs) transplanted into an ischemic environment and effectively enhances angiogenesis. Here, we applied NSCs expressing VEGF (SV-VEGF-NSCs) to treat neuropathic pain. In this study, our goal was to verify the therapeutic effect of SV-VEGF-NSCs by transplanting the cells in a sciatic nerve injury model. We compared the amount of VEGF secreted from DsRed-NSCs (control) or SV-VEGF-NSCs and observed that SV-VEGF-NSCs have a much higher expression level of VEGF. We next investigated whether transplantation with SV-VEGF-NSCs aids functional recovery and pain reduction. We confirmed that transplantation with SV-VEGF-NSCs enhances functional recovery, pain reduction, and remyelination as well as the number of blood vessels compared with the control groups. Our results show that VEGF aids functional recovery and pain reduction in a sciatic nerve injury model. PMID:25793634

  3. Reduced glutamatergic currents and dendritic branching of layer 5 pyramidal cells contribute to medial prefrontal cortex deactivation in a rat model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Crystle Joann Kelly

    2016-05-01

    Full Text Available Multiple studies have demonstrated that neuropathic pain is associated with major reorganization in multiple brain areas. In line with the strong emotional salience of chronic pain, involvement of the limbic system appears particularly important. Within the past few years, it has become clear that the functional deactivation of the prefrontal cortex is critical for both the cognitive/emotional and the sensory components of pain. However, at the cellular level, details of this deactivation remain in large part unclear. Here we show that one week after a peripheral neuropathic injury (Spared Nerve Injury model pyramidal cells in layer 5 of the rat medial prefrontal cortex show responses to excitatory glutamatergic inputs that are reduced by about 50%, as well as reduced frequency of spontaneous excitatory synaptic currents. Additionally, these cells have reduced membrane capacitance and increased input resistance. All these findings are consistent with decreased dendritic length, thus we performed a detailed morphological analysis on a subset of the recorded neurons. We found that the apical dendrites proximal to the soma (excluding the tuft are shorter and less complex in SNI animals, in agreement with the reduced capacitance and glutamatergic input. Finally, we used in-vivo microdialysis to compare the basal concentrations of glutamate and GABA in the prefrontal cortex of sham and SNI rats and found that ambient glutamate is decreased in SNI rats. Taken together, these data show that impaired glutamatergic transmission contributes to the functional deactivation of the mPFC in neuropathic pain. Additionally, the reduced branching of apical dendrites of layer 5 pyramidal neurons may underlay the gray matter reduction in chronic pain.

  4. Sympathetic activity-mediated neuropathic facial pain following simple tooth extraction: a case report.

    Science.gov (United States)

    Kohjitani, Atsushi; Miyawaki, Takuya; Kasuya, Keigo; Shimada, Masahiko

    2002-04-01

    This is a report of a case of sympathetic activity-mediated neuropathic facial pain induced by a traumatic trigeminal nerve injury and by varicella zoster virus infection, following a simple tooth extraction. The patient had undergone extraction of the right lower third molar at a local dental clinic, and soon after the tooth extraction, she became aware of spontaneous pain in the right ear, right temporal region, and in the tooth socket. At our initial examination 30 days after the tooth extraction, the healing of the tooth socket was normal; however, the patient had a tingling and burning sensation (dysesthesia) and spontaneous pain of the right lower lip and the right temporal region, both of which were exacerbated by non-noxious stimuli (allodynia). The patient also showed paralysis of the marginal mandibular branch of the facial nerve, taste dysfunction, and increased varicella zoster serum titers. A diagnostic stellate ganglion block (SGB) 45 days after the tooth extraction using one percent lidocaine markedly alleviated the dysesthesia and allodynia. These symptoms are characteristic of neuropathic pain with sympathetic interaction. The patient was successfully treated with SGB and a tricyclic antidepressant. PMID:12002830

  5. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice

    Directory of Open Access Journals (Sweden)

    Woojin Kim

    2016-01-01

    Full Text Available Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.. BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36 or morphine (0.5, 2, and 5 mg/kg, i.p. alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg or 5-HT3 (MDL-72222, 15 μg receptor antagonist, but not with α2-adrenergic (idazoxan, 10 μg receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain.

  6. Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice.

    Science.gov (United States)

    Kim, Woojin; Kim, Min Joon; Go, Donghyun; Min, Byung-Il; Na, Heung Sik; Kim, Sun Kwang

    2016-02-01

    Oxaliplatin, a chemotherapeutic drug for colorectal cancer, induces severe peripheral neuropathy. Bee venom acupuncture (BVA) has been used to attenuate pain, and its effect is known to be mediated by spinal noradrenergic and serotonergic receptors. Morphine is a well-known opioid used to treat different types of pain. Here, we investigated whether treatment with a combination of these two agents has an additive effect on oxaliplatin-induced neuropathic pain in mice. To assess cold and mechanical allodynia, acetone and von Frey filament tests were used, respectively. Significant allodynia signs were observed three days after an oxaliplatin injection (6 mg/kg, i.p.). BVA (0.25, 1, and 2.5 mg/kg, s.c., ST36) or morphine (0.5, 2, and 5 mg/kg, i.p.) alone showed dose-dependent anti-allodynic effects. The combination of BVA and morphine at intermediate doses showed a greater and longer effect than either BVA or morphine alone at the highest dose. Intrathecal pretreatment with the opioidergic (naloxone, 20 μg) or 5-HT3 (MDL-72222, 15 μg) receptor antagonist, but not with α2 adrenergic (idazoxan, 10 μg) receptor antagonist, blocked this additive effect. Therefore, we suggest that the combination effect of BVA and morphine is mediated by spinal opioidergic and 5-HT3 receptors and this combination has a robust and enduring analgesic action against oxaliplatin-induced neuropathic pain. PMID:26805884

  7. Neuropathic pain develops normally in mice lacking both Nav1.7 and Nav1.8

    Directory of Open Access Journals (Sweden)

    Stirling L Caroline

    2005-08-01

    Full Text Available Abstract Two voltage gated sodium channel α-subunits, Nav1.7 and Nav1.8, are expressed at high levels in nociceptor terminals and have been implicated in the development of inflammatory pain. Mis-expression of voltage-gated sodium channels by damaged sensory neurons has also been implicated in the development of neuropathic pain, but the role of Nav1.7 and Nav1.8 is uncertain. Here we show that deleting Nav1.7 has no effect on the development of neuropathic pain. Double knockouts of both Nav1.7 and Nav1.8 also develop normal levels of neuropathic pain, despite a lack of inflammatory pain symptoms and altered mechanical and thermal acute pain thresholds. These studies demonstrate that, in contrast to the highly significant role for Nav1.7 in determining inflammatory pain thresholds, the development of neuropathic pain does not require the presence of either Nav1.7 or Nav1.8 alone or in combination.

  8. Update on neuropathic pain treatment for trigeminal neuralgia

    OpenAIRE

    Al-Quliti, Khalid W.

    2015-01-01

    Trigeminal neuralgia is a syndrome of unilateral, paroxysmal, stabbing facial pain, originating from the trigeminal nerve. Careful history of typical symptoms is crucial for diagnosis. Most cases are caused by vascular compression of the trigeminal root adjacent to the pons leading to focal demyelination and ephaptic axonal transmission. Brain imaging is required to exclude secondary causes. Many medical and surgical treatments are available. Most patients respond well to pharmacotherapy; car...

  9. A positron emission tomography study of wind-up pain in chronic postherniotomy pain

    DEFF Research Database (Denmark)

    Kupers, Ron; Lonsdale, Markus Georg; Aasvang, Eske Kvanner;

    2011-01-01

    -induced wind-up pain in neuropathic pain patients. We therefore used positron emission tomography (PET) to investigate the cerebral response pattern of mechanical wind-up pain in a homogenous group of 10 neuropathic pain patients with long-standing postherniotomy pain in the groin area. Patients were scanned......) and the brain stem. A direct comparison between wind-up pain and pressure pain revealed that both activated a largely overlapping network. Since no de novo brain areas were activated by wind-up pain, our data suggest that the processes specific to wind-up pain do not occur at the cerebral level....

  10. Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission

    Institute of Scientific and Technical Information of China (English)

    LIU Chang; GUO Qu-lian; HUANG Chang-sheng; ZOU Wang-yuan; SONG Zong-bin

    2013-01-01

    Background Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level.The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters,which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT).Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission.SNAP-25,which is one of the SNARE complexes,can modulate the release of neurotransmitters.Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS.The role of SNAP-25 and GLT as well as GAT is not clearly understood.Methods We used the rat chronic constriction injury (CCI) model for research,and degraded SNAP-25 by a single intrathecal administration of BoNT/A.The mechanical (MWT) and thermal withdrawal latency (TWL) were tested.The level of SNAP-25,GLT,and GAT-1 were assayed using RT-PCR and Western blotting.Results SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP-25 was correlated with the relief of nociceptive responses in CCI rats.MWT and TWL returned to normal from the 5th to 14th day (P <0.05) after the administration.On the 14th day after surgery,compared to the sham group,the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P <0.05).The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.Conclusions SNAP-25 and GLT play important roles in the development of neuropathic pain,and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury.Intrathecal administration of BoNT/A reversed the

  11. Melatonin in Chronic Pain Syndromes.

    Science.gov (United States)

    Danilov, Andrei; Kurganova, Julia

    2016-06-01

    Melatonin is a neurohormone secreted by epiphysis and extrapineal structures. It performs several functions including chronobiotic, antioxidant, oncostatic, immune modulating, normothermal, and anxiolytic functions. Melatonin affects the cardiovascular system and gastrointestinal tract, participates in reproduction and metabolism, and body mass regulation. Moreover, recent studies have demonstrated melatonin efficacy in relation to pain syndromes. The present paper reviews the studies on melatonin use in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The paper discusses the possible mechanisms of melatonin analgesic properties. On one hand, circadian rhythms normalization results in sleep improvement, which is inevitably disordered in chronic pain syndromes, and activation of melatonin adaptive capabilities. On the other hand, there is evidence of melatonin-independent analgesic effect involving melatonin receptors and several neurotransmitter systems. PMID:26984272

  12. Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain

    OpenAIRE

    Meske, Diana S.; Xie, Jennifer Y.; Oyarzo, Janice; Badghisi, Hamid; Ossipov, Michael H.; Porreca, Frank

    2013-01-01

    Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.) morphine (10 mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male, Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery. Additionally, the effects of these drugs on...

  13. Managing painful chronic wounds: the Wound Pain Management Model

    DEFF Research Database (Denmark)

    Price, Patricia; Fogh, Karsten; Glynn, Chris;

    2007-01-01

    document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr......Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...

  14. Mechanisms-based classifications of musculoskeletal pain: part 2 of 3: symptoms and signs of peripheral neuropathic pain in patients with low back (± leg) pain.

    LENUS (Irish Health Repository)

    Smart, Keith M

    2012-08-01

    As a mechanisms-based classification of pain \\'peripheral neuropathic pain\\' (PNP) refers to pain arising from a primary lesion or dysfunction in the peripheral nervous system. Symptoms and signs associated with an assumed dominance of PNP in patients attending for physiotherapy have not been extensively studied. The purpose of this study was to identify symptoms and signs associated with a clinical classification of PNP in patients with low back (± leg) pain. Using a cross-sectional, between-subjects design; four hundred and sixty-four patients with low back (± leg) pain were assessed using a standardised assessment protocol. Patients\\' pain was assigned a mechanisms-based classification based on experienced clinical judgement. Clinicians then completed a clinical criteria checklist specifying the presence or absence of various clinical criteria. A binary logistic regression analysis with Bayesian model averaging identified a cluster of two symptoms and one sign predictive of PNP, including: \\'Pain referred in a dermatomal or cutaneous distribution\\

  15. Effects of Intravenous Ketamine Infusions in a Neuropathic Pain Patient with Lichen Sclerosus et Atrophicus.

    Science.gov (United States)

    Hanna, Ashraf F; Armstrong, Josh S; Smith, Adam J

    2016-01-01

    A patient reported to the Florida Spine Institute (Clearwater, Fla., USA) with severe lichen sclerosus of the anogenital region and legs. The patient's pain presentation was neuropathic with hypersensitivity, allodynia, swelling, and weakness. The patient had failed multiple pain management modalities including opioid therapy, anticonvulsants, and antidepressants. The patient completed a standard intravenous ketamine infusion regimen developed at the Florida Spine Institute and reported complete abolishment of her pain syndrome. For the first time, we report that ketamine infusions also dramatically improved a patient's lichen sclerosus. That ketamine is known to have immunomodulatory properties, and given the clinical observations described in this case report, suggests that ketamine should be explored as a possible new therapeutic option for managing lichen sclerosus, especially in cases that are refractory to conventional therapies. PMID:27462225

  16. Untangling nociceptive, neuropathic and neuroplastic mechanisms underlying the biological domain of back pain.

    Science.gov (United States)

    Hush, Julia M; Stanton, Tasha R; Siddall, Philip; Marcuzzi, Anna; Attal, Nadine

    2013-05-01

    SUMMARY Current clinical practice guidelines advocate a model of diagnostic triage for back pain, underpinned by the biopsychosocial paradigm. However, limitations of this clinical model have become apparent: it can be difficult to classify patients into the diagnostic triage categories; patients with 'nonspecific back pain' are clearly not a homogenous group; and mean effects of treatments based on this approach are small. In this article, it is proposed that the biological domain of the biopsychosocial model needs to be reconceptualized using a neurobiological mechanism-based approach. Recent evidence about nociceptive and neuropathic contributors to back pain is outlined in the context of maladaptive neuroplastic changes of the somatosensory system. Implications for clinical practice and research are discussed.

  17. Effects of Intravenous Ketamine Infusions in a Neuropathic Pain Patient with Lichen Sclerosus et Atrophicus

    Science.gov (United States)

    Hanna, Ashraf F.; Armstrong, Josh S.; Smith, Adam J.

    2016-01-01

    A patient reported to the Florida Spine Institute (Clearwater, Fla., USA) with severe lichen sclerosus of the anogenital region and legs. The patient's pain presentation was neuropathic with hypersensitivity, allodynia, swelling, and weakness. The patient had failed multiple pain management modalities including opioid therapy, anticonvulsants, and antidepressants. The patient completed a standard intravenous ketamine infusion regimen developed at the Florida Spine Institute and reported complete abolishment of her pain syndrome. For the first time, we report that ketamine infusions also dramatically improved a patient's lichen sclerosus. That ketamine is known to have immunomodulatory properties, and given the clinical observations described in this case report, suggests that ketamine should be explored as a possible new therapeutic option for managing lichen sclerosus, especially in cases that are refractory to conventional therapies. PMID:27462225

  18. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    Directory of Open Access Journals (Sweden)

    Karine Thibault

    Full Text Available Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  19. Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

    OpenAIRE

    Carlo Luca Romanò; Delia Romanò; Marco Lacerenza

    2012-01-01

    Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published p...

  20. Neuropathic pain induced by spinal cord injury: Role of endothelin ETA and ETB receptors.

    Science.gov (United States)

    Forner, S; Martini, A C; de Andrade, E L; Rae, G A

    2016-03-23

    Spinal cord injury (SCI) is a devastating neurologic disorder that often inflicts neuropathic pain, which further impacts negatively on the patient's quality of life. Endothelin peptides, which exert their effects via endothelin A (ETAR) and endothelin B (ETBR) receptors, can contribute to sensory changes associated with inflammatory and neuropathic pain, but their role in nociception following SCI is unknown. At different time points after subjecting male Wistar rats to surgery for compression-induced T10 level SCI, the spinal cord levels of ETAR and ETBR were assessed by Western blot and immunohistochemistry, and the corresponding mRNAs by real-time PCR, alongside recordings of behavioural responses to mechanical stimulation of the hind paws with von Frey hairs. SCI was associated with development of hind paw mechanical allodynia from day 14 onwards, and up-regulation of ETAR and ETBR mRNA in the spinal cord and dorsal root ganglia, and of ETAR protein in the spinal cord. SCI increased ETAR protein expression in spinal grey matter. Treatment on day 21 after surgery with the ETAR selective antagonist BQ-123 (40 and 90pmol, intrathecally) or the dual ETAR/ETBR antagonist bosentan (30 and 100mg/kg, orally) transiently reduced SCI-induced mechanical allodynia, but the ETBR antagonist BQ-788 was ineffective. Altogether, these data show that SCI upregulates ETAR expression in the spinal cord, which appears to contribute to the hind paw mechanical allodynia associated with this condition. Therapies directed towards blockade of spinal ETAR may hold potential to limit SCI-induced neuropathic pain. PMID:26861196

  1. Comprehensive management of chronic pain in haemophilia.

    Science.gov (United States)

    Young, G; Tachdjian, R; Baumann, K; Panopoulos, G

    2014-03-01

    Chronic pain, most often due to haemophilic arthropathy, is a pervasive problem in persons with haemophilia (PWH) that adversely impacts function and quality of life. PWH with inhibitors and older PWH may be especially vulnerable to progressive arthropathy and resulting chronic pain. The development of chronic pain from acute pain involves a complex interplay of biological and psychosocial factors that may all contribute to the perpetuation of chronic pain and the outcome of therapy. In the absence of evidence-based guidelines, an individualized, multimodal approach to chronic pain management is proposed, as it is in individuals without haemophilia who have chronic pain. Pharmacological treatment is central to the management of chronic pain and must be modified based on pain intensity, ongoing response to therapy and the risk for adverse events. Non-pharmacological interventions, including physiotherapy, complementary treatments and surgical (e.g. orthopaedic) or other invasive procedures, may be integral to chronic pain management in this population. Ongoing psychosocial assessment is critical to identify those factors that may be contributing to the perpetuation of chronic pain or acting as barriers to effective management. Additional study is needed to identify optimal pharmacological treatments for chronic pain in PWH based on the unique pathophysiology of haemophilic arthropathy and on risk profile. Systematic determination of the particular psychosocial factors impacting the experience and management of chronic pain in PWH would likewise add value to the treatment of this pervasive problem.

  2. Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005

    Directory of Open Access Journals (Sweden)

    Carroll Dawn

    2008-05-01

    Full Text Available Abstract Background Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain. Methods A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923; trigeminal neuralgia (1,862; phantom limb pain (57 and painful diabetic neuropathy (1,444 using computerised UK general practice records (THIN: May 2002 to July 2005. Results Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI 27–30 for post-herpetic neuralgia, 27 (95%CI 26–29 for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1 for phantom limb pain and 21 (95%CI 20–22 for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy and opioid analgesics (phantom limb pain. The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain. Conclusion The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.

  3. Miofacialni bolečinski sindrom in sindrom fibromialgije: Myofascial pain syndrome and fibromyalgia syndrome: Nonpharmacological treatment of chronic low back pain: practice and possibilities for treatment: razlikovanje v klinični praksi in možnosti obravnave:

    OpenAIRE

    Jamnik, Helena

    2010-01-01

    Fibromyalgia is a chronic syndrome that is characterized by widespread body pain. The prevalence of fibromyalgia syndrome in the general population is estimated to be 2-7%. Chronic pain is often associated with comorbidities suchas depression, chronic fatigue, anxiety. With the new evidence regarding the pathophysiology of the fibromyalgia syndrome, it has been suggested that it may be one of the neuropathic pain syndromes. Although the pathogenesis is not completely understood, it has been s...

  4. Spinal astrocytic activation contributes to mechanical allodynia in a rat chemotherapy-induced neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Xi-Tuan Ji

    Full Text Available Chemotherapy-induced neuropathic pain (CNP is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor; whereas minocycline (microglial specific inhibitor had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat. Furthermore, oxidative stress mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR phosphorylation in spinal neurons to strengthen pain transmission. Taken together, our findings suggest that spinal activated astrocytes may be a crucial component of the pathophysiology of CNP and "Astrocyte-Cytokine-NMDAR-neuron" pathway may be one detailed neural mechanisms underlying CNP. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for treating CNP.

  5. The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence

    Directory of Open Access Journals (Sweden)

    de León-Casasola OA

    2016-02-01

    Full Text Available Oscar A de León-Casasola,1,2 Victor Mayoral3 1Department of Anesthesiology, Division of Pain Medicine, Roswell Park Cancer Institute, 2University at Buffalo, School of Medicine and Biomedical Sciences. NY, USA; 3Anesthesiology Department, Pain Management Unit, University Hospital of Bellvitge, L'Hospitalet de Llobregat, Spain Abstract: Topical 5% lidocaine medicated plasters represent a well-established first-line option for the treatment of peripheral localized neuropathic pain (LNP. This review provides an updated overview of the clinical evidence (randomized, controlled, and open-label clinical studies, real-life daily clinical practice, and case series. The 5% lidocaine medicated plaster effectively provides pain relief in postherpetic neuralgia, and data from a large open-label controlled study indicate that the 5% lidocaine medicated plaster is as effective as systemic pregabalin in postherpetic neuralgia and painful diabetic polyneuropathy but with an improved tolerability profile. Additionally, improved analgesia and fewer side effects were experienced by patients treated synchronously with the 5% lidocaine medicated plaster, further demonstrating the value of multimodal analgesia in LNP. The 5% lidocaine medicated plaster provides continued benefit after long-term (≤7 years use and is also effective in various other LNP conditions. Minor application-site reactions are the most common adverse events associated with the 5% lidocaine medicated plaster; there is minimal risk of systemic adverse events and drug–drug interactions. Although further well-controlled studies are warranted, the 5% lidocaine medicated plaster is efficacious and safe in LNP and may have particular clinical benefit in elderly and/or medically compromised patients because of the low incidence of adverse events. Keywords: 5% lidocaine medicated plaster, clinical evidence, localized neuropathic pain, postherpetic neuralgia, review

  6. Relationships between changes in pain severity and other patient-reported outcomes: an analysis in patients with posttraumatic peripheral neuropathic pain

    OpenAIRE

    Zlateva Gergana; Morlion Bart; Bach Flemming W; Serpell Michael; van Seventer Robert; Bushmakin Andrew G; Cappelleri Joseph C; Nimour Meryem

    2011-01-01

    Abstract Background The objective of this study is to use the pain numeric rating scale (NRS) to evaluate associations between change in pain severity and changes in sleep, function, and mood assessed via patient-reported outcomes (PROs) in patients with posttraumatic pain. Methods This is a secondary analysis of a clinical trial evaluating pregabalin in patients with posttraumatic peripheral neuropathic pain (N = 254). Regression models were used to determine associations between changes in ...

  7. Ultramicronized Palmitoylethanolamide (PEA) in spinal cord injury neuropathic pain: a randomized controlled trial

    DEFF Research Database (Denmark)

    Andresen, Sven Robert; Bing, Jette; Hansen, Rikke Bod Middelhede;

    2015-01-01

    . Methods  A randomized, double-blind, placebo-controlled parallel multicenter study. Study population of at least 66 patients must complete the 12 week trial.Questionnaires regarding neuropathic pain, spasticity, insomnia, anxiety and depression are completed before and after treatment. A numeric...... is 55.3 (±9.5) years and average time since injury is 8.8 (±8.9)years. Causes of injury are 31% transport, 27% fall, 21% non-traumatic SCI, 14% other traumatic cause and 7% sports injuries. No major side effectshave been reported. Further results will be presented at the meeting...

  8. Cannabinoids and centrak neuropathic pain. A review (Cannabinoidi e dolore neuropatico centrale. Una rassegna

    Directory of Open Access Journals (Sweden)

    Francesco Crestani

    2014-03-01

    Full Text Available Only recently, the medical community highlighted the pharmacological scientific bases of the effects of Cannabis. The most important active principle, Delta-9-tetrahydrocannabinol was identified in the second half of the last century, and receptors were subsequently identified and endogenous ligands, called endocannabinoids, were characterized. The effectiveness of the cannabinoids in the treatment of nausea and vomit due to anti-neoplastic chemotherapy and in the wasting-syndrome during AIDS is recognized. Moreover, the cannabinoids have shown analgesic properties, particularly interesting with regard to the central neuropathic pain. This article will review the current knowledge and will give practical guidance on how to proceed in prescribing cannabinoids.

  9. Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain.

    Science.gov (United States)

    Drizin, Irene; Gregg, Robert J; Scanio, Marc J C; Shi, Lei; Gross, Michael F; Atkinson, Robert N; Thomas, James B; Johnson, Matthew S; Carroll, William A; Marron, Brian E; Chapman, Mark L; Liu, Dong; Krambis, Michael J; Shieh, Char-Chang; Zhang, XuFeng; Hernandez, Gricelda; Gauvin, Donna M; Mikusa, Joseph P; Zhu, Chang Z; Joshi, Shailen; Honore, Prisca; Marsh, Kennan C; Roeloffs, Rosemarie; Werness, Stephen; Krafte, Douglas S; Jarvis, Michael F; Faltynek, Connie R; Kort, Michael E

    2008-06-15

    The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated sodium channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a rodent model of neuropathic pain, together with improved CNS and cardiovascular safety profiles compared to the clinically used sodium channel blockers mexiletine and lamotrigine. PMID:18501613

  10. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    OpenAIRE

    Lekha Saha; Debasish Hota; Amitava Chakrabarti

    2012-01-01

    Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i....

  11. Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain

    OpenAIRE

    Gutierrez, Tannia; Crystal, Jonathon D.; Zvonok, Alexander M.; Makriyannis, Alexandros; Hohmann, Andrea G.

    2011-01-01

    Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB2 agonist to attenuate a neuropathic pain state. Self-medication of the CB2 agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal threshol...

  12. Chronic pelvic pain: comorbidity between chronic musculoskeletal pain and vulvodynia

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    G. Biasi

    2014-06-01

    Full Text Available Chronic pelvic pain (CPP is a common condition that has a major impact on the quality of life of both men and women. Male CPP is usually attributable to well-defined urogenital conditions (most frequently infectious/non infectious prostatic diseases or musculoskeletal or bowel diseases, whereas the features of female CPP are much more complex and are of particular clinical and epidemiological importance. It is a multifactorial syndrome that can be due to diseases of the urogenital, gastrointestinal, or musculoskeletal systems, or to neurological or neuropsychiatric disorders. It is not always easy to identify its predominant pathogenesis, although it often occurs as a central sensitization syndrome triggered by an initial stimulus which is no longer detectable and only manifests itself clinically through pain. In this respect, there are some very interesting relationships between vulvodynia and fibromyalgic syndrome, as identified in a preliminary study of women with chronic musculoskeletal pain in which it was demonstrated that vulvar pain plays an important role, although it is often overlooked and undiagnosed.

  13. Perspectives on physiotherapy guidelines for chronic low back pain

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    P. Berger

    2007-02-01

    Full Text Available The prevalence of chronic low back pain presents a world widedilemma to patients, physiotherapists and clinicians. There is scant evidence for prevention and treatment however it is now acknowledged that the use of  physiotherapy in a multidimensional context has proved the more appropriate model as a vital component of the collaborative approach required for effective pain management. The following article reviews the current literature, evaluates and combines the guidelines that have been proposed from various international studies to provide a practical approach to the management of chronic back pain. This approach recognizes a broad biopsychosocial model of health and the positive role of activity in health and healing with emphasis on function, rather than impairment. Therefore the development of a patient-centred rehabilitative approach has emerged that emphasizes the restoration of normal movement and function with the addition of physical modalities where appropriate. Recent advances in neurophysiology, the modulation of pain and its perception and the fact that biological systems are known to be greatly affected by electrical treatment provide a clearer rationale for the use of physical agents for rehabilitation of patients with pain and relateddisability. The modalities used in conjunction with active exercises include thermal, massage, electrical stimulation, traction, transcutaneous electrical nerve stimulation (Tens, myofascial release, dry needling, mobilization and acupuncture. An algorithm is provided with the intention of developing protocols for breaking the pain cycle in both nociceptive and neuropathic pain states and in reducing inflammation which is a component of both peripheral and central sensitization. Pain rehabilitation is a useful and cost-effective approach to chronic pain management and makes patients’ responsible partners in their own progress. It encourages planning, pacing of activities and activity related

  14. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment

    Science.gov (United States)

    Ahlbeck, Karsten; Aldington, Dominic; Alon, Eli; Coluzzi, Flaminia; Dahan, Albert; Huygen, Frank; Kocot-Kępska, Magdalena; Mangas, Ana Cristina; Mavrocordatos, Philippe; Morlion, Bart; Müller-Schwefe, Gerhard; Nicolaou, Andrew; Pérez Hernández, Concepción; Sichère, Patrick; Schäfer, Michael; Varrassi, Giustino

    2013-01-01

    Chronic pain is currently under-diagnosed and under-treated, partly because doctors’ training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain. PMID:23786498

  15. Building a diagnostic algorithm on localized neuropathic pain (LNP and targeted topical treatment: focus on 5% lidocaine-medicated plaster

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    Casale R

    2014-04-01

    Full Text Available Roberto Casale,1,2 Consalvo Mattia31Department of Clinical Neurophysiology and Pain Rehabilitation Unit, Foundation “Salvatore Maugeri”, Research and Care Institute, IRCCS, Pavia, Italy; 2EFIC Montescano Pain School, Montescano, Italy; 3Department of Medical-Surgical Sciences, Section of Anaesthesia, Intensive Care and Pain Medicine, Faculty of Medicine and Pharmacy, Sapienza University of Rome, ItalyAbstract: Within the broad definition of neuropathic pain, the refinement of clinical diagnostic procedures has led to the introduction of the concept of localized neuropathic pain (LNP. It is characterized by consistent and circumscribed area(s of maximum pain, which are associated with negative or positive sensory signs and/or spontaneous symptoms typical of neuropathic pain. This description outlines the clinical features (currently lacking in guidelines and treatment recommendations in patients for whom topical targeted treatment with 5% lidocaine-medicated plaster is suggested as first-line therapy. Few epidemiologic data are present in the literature but it is generally estimated that about 60% of neuropathic pain conditions are localized, and therefore identifiable as LNP. A mandatory clinical criterion for the diagnosis of LNP is that signs and symptoms must be present in a clearly identified and defined area(s. Cartographic recordings can help to define each area and to assess variations. The diagnosis of LNP relies on careful neurological examination more than on pain questionnaires, but it is recognized that they can be extremely useful for recording the symptom profiles and establishing a more targeted treatment. The most widely studied frequent/relevant clinical presentations of LNP are postherpetic neuralgia, diabetic neuropathy, and neuropathic postoperative pain. They successfully respond to treatment with 5% lidocaine-medicated plaster with equal if not better pain control but with fewer side effects versus conventional systemic

  16. Role of PAF receptor in proinflammatory cytokine expression in the dorsal root ganglion and tactile allodynia in a rodent model of neuropathic pain.

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    Shigeo Hasegawa

    Full Text Available BACKGROUND: Neuropathic pain is a highly debilitating chronic pain following damage to peripheral sensory neurons and is often resistant to all treatments currently available, including opioids. We have previously shown that peripheral nerve injury induces activation of cytosolic phospholipase A(2 (cPLA(2 in injured dorsal root ganglion (DRG neurons that contribute to tactile allodynia, a hallmark of neuropathic pain. However, lipid mediators downstream of cPLA(2 activation to produce tactile allodynia remain to be determined. PRINCIPAL FINDINGS: Here we provide evidence that platelet-activating factor (PAF is a potential candidate. Pharmacological blockade of PAF receptors (PAFRs reduced the development and expression of tactile allodynia following nerve injury. The expression of PAFR mRNA was increased in the DRG ipsilateral to nerve injury, which was seen mainly in macrophages. Furthermore, mice lacking PAFRs showed a reduction of nerve injury-induced tactile allodynia and, interestingly, a marked suppression of upregulation of tumor necrosis factor alpha (TNFalpha and interleukin-1beta (IL-1beta expression in the injured DRG, crucial proinflammatory cytokines involved in pain hypersensitivity. Conversely, a single injection of PAF near the DRG of naïve rats caused a decrease in the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner and an increase in the expression of mRNAs for TNFalpha and IL-1beta, both of which were inhibited by pretreatment with a PAFR antagonist. CONCLUSIONS: Our results indicate that the PAF/PAFR system has an important role in production of TNFalpha and IL-1beta in the DRG and tactile allodynia following peripheral nerve injury and suggest that blocking PAFRs may be a viable therapeutic strategy for treating neuropathic pain.

  17. [Association between chronic pain and depression].

    Science.gov (United States)

    Alonso Fernández, Francisco

    2005-01-01

    The comorbidity integrated by chronic pain and depression is very common. The somatoform depressive symptoms appear often as diferent types of pain. Amon them premenstrual pain and fibromialgia are some of the most important clinical pictures. Chronic pain leads to depression as a consequence of these three kinds of factors: biomedical, psychosocial (passive attitude, disability) and pharmacological agents. Copping and acceptance of chronic pain is associated with lower pain intensity, less depression and less psychosocial disability. The appropriate use of analgesics in the management of chronic pain demands individualization. Several antidepressants have possitive effects on pain syndrom. Depression is underrecognized ad undertreated above all in patients with chronic pain. In order screening the depression seven ways are described here: personal and family history, type of the personality, clinic and evolutive aspects of somatoform symptom, search of other depressive symptoms and positive therapeutic effect determinated by an antidepressant.

  18. Current Status of the New Antiepileptic Drugs in Chronic Pain

    Science.gov (United States)

    Sidhu, Harpreet S.; Sadhotra, Akshay

    2016-01-01

    Antiepileptic drugs (AEDs) are extensively used worldwide to treat a wide range of disorders other than epilepsy, such as neuropathic pain, migraine, and bipolar disorder. Due to this situation more than 20 new third-generation AEDs have been introduced in the market recently. The future design of new AEDs must also have potential to help in the non-epileptic disorders. The wide acceptance of second generation AEDs for the management of various non-epileptic disorders has caused the emergence of generics in the market. The wide use of approved AEDs outside epilepsy is based on both economic and scientific reasons. Bipolar disorders, migraine prophylaxis, fibromyalgia, and neuropathic pain represent the most attractive indication expansion opportunities for anticonvulsant developers, providing blockbuster revenues. Strong growth in non-epilepsy conditions will see Pfizer’s Lyrica become the market leading brand by 2018. In this review, we mainly focus on the current status of new AEDs in the treatment of chronic pain and migraine prophylaxis. AEDs have a strong analgesic potential and this is demonstrated by the wide use of carbamazepine in trigeminal neuralgia and sodium valproate in migraine prophylaxis. At present, data on the new AEDs for non-epileptic conditions are inconclusive. Not all AEDs are effective in the management of neuropathic pain and migraine. Only those AEDs whose mechanisms of action are match with pathophysiology of the disease, have potential to show efficacy in non-epileptic disorder. For this better understanding of the pathophysiology of the disease and mechanisms of action of new AEDs are essential requirement before initiating pre-clinical and clinical trials. Many new AEDs show good results in the animal model and open-label studies but fail to provide strong evidence at randomized, placebo-controlled trials. The final decision regarding the clinical efficacy of the particular AEDs in a specific non-epileptic disorder should be

  19. Anthropogenic Radio-Frequency Electromagnetic Fields Elicit Neuropathic Pain in an Amputation Model

    Science.gov (United States)

    Jones, Erick; Romero-Ortega, Mario

    2016-01-01

    Anecdotal and clinical reports have suggested that radio-frequency electromagnetic fields (RF EMFs) may serve as a trigger for neuropathic pain. However, these reports have been widely disregarded, as the epidemiological effects of electromagnetic fields have not been systematically proven, and are highly controversial. Here, we demonstrate that anthropogenic RF EMFs elicit post-neurotomy pain in a tibial neuroma transposition model. Behavioral assays indicate a persistent and significant pain response to RF EMFs when compared to SHAM surgery groups. Laser thermometry revealed a transient skin temperature increase during stimulation. Furthermore, immunofluorescence revealed an increased expression of temperature sensitive cation channels (TRPV4) in the neuroma bulb, suggesting that RF EMF-induced pain may be due to cytokine-mediated channel dysregulation and hypersensitization, leading to thermal allodynia. Additional behavioral assays were performed using an infrared heating lamp in place of the RF stimulus. While thermally-induced pain responses were observed, the response frequency and progression did not recapitulate the RF EMF effects. In vitro calcium imaging experiments demonstrated that our RF EMF stimulus is sufficient to directly contribute to the depolarization of dissociated sensory neurons. Furthermore, the perfusion of inflammatory cytokine TNF-α resulted in a significantly higher percentage of active sensory neurons during RF EMF stimulation. These results substantiate patient reports of RF EMF-pain, in the case of peripheral nerve injury, while confirming the public and scientific consensus that anthropogenic RF EMFs engender no adverse sensory effects in the general population. PMID:26760033

  20. Hypnotherapy for the Management of Chronic Pain

    OpenAIRE

    Elkins, Gary; Jensen, Mark P.; Patterson, David R.

    2007-01-01

    This article reviews controlled prospective trials of hypnosis for the treatment of chronic pain. Thirteen studies, excluding studies of headaches, were identified that compared outcomes from hypnosis for the treatment of chronic pain to either baseline data or a control condition. The findings indicate that hypnosis interventions consistently produce significant decreases in pain associated with a variety of chronic-pain problems. Also, hypnosis was generally found to be more effective than ...

  1. Electronic momentary assessment in chronic pain 1: psychological pain responses as predictors of pain intensity

    OpenAIRE

    Sorbi, M.J.; Peters, M.L.; Kruise, D.A.; Maas, C.J.M.; Kerssens, J. J.; Verhaak, P.F.M.; BENSING, J

    2006-01-01

    Objectives and Methods: Electronic momentary assessment was employed to substantiate the relevance of psychological functioning in chronic pain. More than 7100 electronic diaries from 80 patients with varying IASP classified types of chronic pain served to investigate to what extent fear-avoidance, cognitive and spousal solicitous and punishing pain responses explained fluctuations in pain intensity and whether patients with pre-chronic, recently chronic and persistently chronic pain differed...

  2. Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain.

    Science.gov (United States)

    Masuda, Takahiro; Ozono, Yui; Mikuriya, Satsuki; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Iwatsuki, Ken; Uneyama, Hisayuki; Ichikawa, Reiko; Salter, Michael W; Tsuda, Makoto; Inoue, Kazuhide

    2016-01-01

    Activation of purinergic receptors in the spinal cord by extracellular ATP is essential for neuropathic hypersensitivity after peripheral nerve injury (PNI). However, the cell type responsible for releasing ATP within the spinal cord after PNI is unknown. Here we show that PNI increases expression of vesicular nucleotide transporter (VNUT) in the spinal cord. Extracellular ATP content ([ATP]e) within the spinal cord was increased after PNI, and this increase was suppressed by exocytotic inhibitors. Mice lacking VNUT did not show PNI-induced increase in [ATP]e and had attenuated hypersensitivity. These phenotypes were recapitulated in mice with specific deletion of VNUT in spinal dorsal horn (SDH) neurons, but not in mice lacking VNUT in primary sensory neurons, microglia or astrocytes. Conversely, ectopic VNUT expression in SDH neurons of VNUT-deficient mice restored PNI-induced increase in [ATP]e and pain. Thus, VNUT is necessary for exocytotic ATP release from SDH neurons which contributes to neuropathic pain. PMID:27515581

  3. Preventive Effects of Bee Venom Derived Phospholipase A₂ on Oxaliplatin-Induced Neuropathic Pain in Mice.

    Science.gov (United States)

    Li, Dongxing; Kim, Woojin; Shin, Dasom; Jung, Yongjae; Bae, Hyunsu; Kim, Sun Kwang

    2016-01-01

    Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A₂ (bvPLA₂) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7-9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA₂ (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA₂ were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA₂ may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs. PMID:26797636

  4. The role of cation-dependent chloride transporters in neuropathic pain following spinal cord injury

    Directory of Open Access Journals (Sweden)

    Rajpal Sharad

    2008-09-01

    Full Text Available Abstract Background Altered Cl- homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl- regulatory proteins, Na+-K+-Cl- cotransporter 1 (NKCC1 and K+-Cl- cotransporter 2 (KCC2, in neuropathic pain following spinal cord injury (SCI. Results Sprague-Dawley rats underwent a contusive SCI at T9 using the MASCIS impactor. The rats developed hyperalgesia between days 21 and 42 post-SCI. Thermal hyperalgesia (TH was determined by a decrease in hindpaw thermal withdrawal latency time (WLT between days 21 and 42 post-SCI. Rats with TH were then treated with either vehicle (saline containing 0.25% NaOH or NKCC1 inhibitor bumetanide (BU, 30 mg/kg, i.p. in vehicle. TH was then re-measured at 1 h post-injection. Administration of BU significantly increased the mean WLT in rats (p Conclusion Taken together, expression of NKCC1 and KCC2 proteins was differentially altered following SCI. The anti-hyperalgesic effect of NKCC1 inhibition suggests that normal or elevated NKCC1 function and loss of KCC2 function play a role in the development and maintenance of SCI-induced neuropathic pain.

  5. Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain.

    Science.gov (United States)

    Seltzman, Herbert H; Shiner, Craig; Hirt, Erin E; Gilliam, Anne F; Thomas, Brian F; Maitra, Rangan; Snyder, Rod; Black, Sherry L; Patel, Purvi R; Mulpuri, Yatendra; Spigelman, Igor

    2016-08-25

    Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with <1% blood-brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of ∼0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain. PMID:27482723

  6. Pharmacodynamic analysis of the analgesic effect of capsaicin 8% patch (QutenzaTM in diabetic neuropathic pain patients: detection of distinct response groups

    Directory of Open Access Journals (Sweden)

    Martini C

    2012-03-01

    Full Text Available Christian Martini1,*, Ashraf Yassen2,*, Erik Olofsen1, Paul Passier2, Malcom Stoker3, Albert Dahan1 1Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands; 2Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands; 3Global Medical Sciences, Astellas Pharma Global Development Europe, Leiderdorp, The Netherlands*These authors contributed equally to this workAbstract: Treatment of chronic pain is associated with high variability in the response to pharmacological interventions. A mathematical pharmacodynamic model was developed to quantify the magnitude and onset/offset times of effect of a single capsaicin 8% patch application in the treatment of painful diabetic peripheral neuropathy in 91 patients. In addition, a mixture model was applied to objectively match patterns in pain-associated behavior. The model identified four distinct subgroups that responded differently to treatment: 3.3% of patients (subgroup 1 showed worsening of pain; 31% (subgroup 2 showed no change; 32% (subgroup 3 showed a quick reduction in pain that reached a nadir in week 3, followed by a slow return towards baseline (16% ± 6% pain reduction in week 12; 34% (subgroup 4 showed a quick reduction in pain that persisted (70% ± 5% reduction in week 12. The estimate of the response-onset rate constant, obtained for subgroups 1, 3, and 4, was 0.76 ± 0.12 week-1 (median ± SE, indicating that every 0.91 weeks the pain score reduces or increases by 50% relative to the score of the previous week (= t½. The response-offset rate constant could be determined for subgroup 3 only and was 0.09 ± 0.04 week-1 (t½ 7.8 weeks. The analysis allowed separation of a heterogeneous neuropathic pain population into four homogenous subgroups with distinct behaviors in response to treatment with capsaicin. It is argued that this model-based approach may have added value in analyzing

  7. Transformation of the output of spinal lamina I neurons after nerve injury and microglia stimulation underlying neuropathic pain

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    Salter Michael W

    2007-09-01

    Full Text Available Abstract Background Disinhibition of neurons in the superficial spinal dorsal horn, via microglia – neuron signaling leading to disruption of chloride homeostasis, is a potential cellular substrate for neuropathic pain. But, a central unresolved question is whether this disinhibition can transform the activity and responses of spinal nociceptive output neurons to account for the symptoms of neuropathic pain. Results Here we show that peripheral nerve injury, local spinal administration of ATP-stimulated microglia or pharmacological disruption of chloride transport change the phenotype of spinal lamina I output neurons, causing them to 1 increase the gain of nociceptive responsiveness, 2 relay innocuous mechanical input and 3 generate spontaneous bursts of activity. The changes in the electrophysiological phenotype of lamina I neurons may account for three principal components of neuropathic pain: hyperalgesia, mechanical allodynia and spontaneous pain, respectively. Conclusion The transformation of discharge activity and sensory specificity provides an aberrant signal in a primarily nociceptive ascending pathway that may serve as a basis for the symptoms of neuropathic pain.

  8. Neurophysiology of pain and hypnosis for chronic pain

    OpenAIRE

    Dillworth, Tiara; Mendoza, M. Elena; Jensen, Mark P.

    2011-01-01

    In the past decade there has been a dramatic increase in (1) understanding the neurophysiological components of the pain experiences, (2) randomized clinical trials testing the efficacy of hypnotic treatments on chronic pain, and (3) laboratory research examining the effects of hypnosis on the neurophysiological processes implicated in pain. Work done in these areas has not only demonstrated the efficacy of hypnosis for treating chronic pain but is beginning to shed light on neurophysiologica...

  9. Chronic widespread pain in spondyloarthritis

    Directory of Open Access Journals (Sweden)

    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.

  10. Symptom profiles in the painDETECT questionnaire in patients with peripheral neuropathic pain stratified according to sensory loss in quantitative sensory testing

    DEFF Research Database (Denmark)

    Vollert, Jan; Kramer, M; Barroso, A;

    2016-01-01

    BACKGROUND: The painDETECT Questionnaire (PDQ) is commonly used as a screening tool to discriminate between neuropathic pain (NP) and nociceptive pain, based on the self-report of symptoms, including pain qualities, numbness and pain to touch, cold or heat. However, there is little data about...... burning sensations and pain evoked by light touch. CONCLUSION: Although the PDQ was not designed to assess sensory loss, single items reflect thermal and / or mechanical sensory loss at group level, but due to substantial variability, the PDQ does not allow for individual allocation of patients...

  11. Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2.

    Science.gov (United States)

    Nissenbaum, Jonathan; Devor, Marshall; Seltzer, Ze'ev; Gebauer, Mathias; Michaelis, Martin; Tal, Michael; Dorfman, Ruslan; Abitbul-Yarkoni, Merav; Lu, Yan; Elahipanah, Tina; delCanho, Sonia; Minert, Anne; Fried, Kaj; Persson, Anna-Karin; Shpigler, Hagai; Shabo, Erez; Yakir, Benjamin; Pisanté, Anne; Darvasi, Ariel

    2010-09-01

    Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca(2+) channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.

  12. Celastrol Attenuates Inflammatory and Neuropathic Pain Mediated by Cannabinoid Receptor Type 2

    Directory of Open Access Journals (Sweden)

    Longhe Yang

    2014-08-01

    Full Text Available Celastrol, a major active ingredient of Chinese herb Tripterygium wilfordii Hook. f. (thunder god vine, has exhibited a broad spectrum of pharmacological activities, including anti-inflammation, anti-cancer and immunosuppression. In the present study, we used animal models of inflammatory pain and neuropathic pain, generated by carrageenan injection and spared nerve injury (SNI, respectively, to evaluate the effect of celastrol and to address the mechanisms underlying pain processing. Intraperitoneal (i.p. injection of celastrol produced a dose-dependent inhibition of carrageenan-induced edema and allodynia. Real-time PCR analysis showed that celastrol (0.3 mg/kg, i.p. significantly reduced mRNA expressions of inflammatory cytokines, TNF-α, IL-6, IL-1β, in carrageenan-injected mice. In SNI mice, pain behavior studies showed that celastrol (1 mg/kg, i.p. effectively prevented the hypersensitivity of mechanical nociceptive response on the third day post-surgery and the seventh day post-surgery. Furthermore, the anti-hyperalgesic effects of celastrol in carrageenan-injected mice and SNI mice were reversed by SR144528 (1 mg/kg, i.p., a specific cannabinoid receptor-2 (CB2 receptor antagonist, but not by SR141716 (1 mg/kg, i.p., a specific cannabinoid receptor-1 (CB1 receptor antagonist. Taken together, our results demonstrate the analgesia effects of celastrol through CB2 signaling and propose the potential of exploiting celastrol as a novel candidate for pain relief.

  13. Future perspectives: pathogenesis of chronic muscle pain.

    Science.gov (United States)

    Staud, Roland

    2007-06-01

    Chronic painful muscle conditions include non-inflammatory and inflammatory illnesses. This review is focused on chronic non-inflammatory pain conditions such as myofascial pain syndrome (MPS) and fibromyalgia syndrome (FM), and will not discuss metabolic, genetic or inflammatory muscle diseases such as McArdle's disease, muscular dystrophy, polymyositis, dermatomyositis, or inclusion body myositis.

  14. Effective management of intractable neuropathic pain using an intrathecal morphine pump in a patient with acute transverse myelitis

    Directory of Open Access Journals (Sweden)

    Wu WT

    2013-07-01

    Full Text Available Wei-Ting Wu,1 Yu-Hui Huang,2,3 Der-Cherng Chen,4 Yu-Hsuan Huang,1 Li-Wei Chou1,5 1Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Department of Physical Medicine and Rehabilitation, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Center of Neuropsychiatry, Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan, 5School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, TaiwanAbstract: Transverse myelitis is a rare inflammatory myelopathy characterized by loss of motor and sensory function below the affected level of the spinal cord, and causes neurogenic bowel and bladder. Occasionally, it also causes neuropathic pain with spasticity. Traditional therapies for neuropathic pain are multiple, including multimodal analgesic regimens, antiepileptic or antidepressant medications, opioids, sympathetic blocks, and spinal cord stimulation. Persistent neuropathic pain can cause emotional distress by affecting sleep, work, recreation, and emotional well-being. Here we report the case of a patient suffering from intractable neuropathic pain following acute transverse myelitis that was not relieved by combinations of nonsteroidal anti-inflammatory, antiepileptic, antidepressant, and opioid medications, or by acupuncture. Implantation of an intrathecal morphine pump controlled the pain successfully without side effects, and enabled the patient to embark on intensive rehabilitation. The patient's muscle strength has improved significantly and the patient may soon be able to use a walker with minimal assistance.Keywords: intrathecal morphine pump, neuropathic pain, rehabilitation, transverse myelitis

  15. Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Andresen, Sven R; Bing, Jette; Hansen, Rikke M; Biering-Sørensen, Fin; Johannesen, Inger L; Hagen, Ellen Merete; Rice, Andrew S C; Nielsen, Jørgen F; Bach, Flemming W; Finnerup, Nanna B

    2016-09-01

    Neuropathic pain and spasticity after spinal cord injury (SCI) represent significant problems. Palmitoylethanolamide (PEA), a fatty acid amide that is produced in many cells in the body, is thought to potentiate the action of endocannabinoids and to reduce pain and inflammation. This randomized, double-blind, placebo-controlled, parallel multicenter study was performed to investigate the effect of ultramicronized PEA (PEA-um) as add-on therapy on neuropathic pain in individuals with SCI. A pain diary was completed and questionnaires were completed before and after the 12-week treatment with either placebo or PEA-um. The primary outcome measure was the change in mean neuropathic pain intensity from the 1-week baseline period to the last week of treatment measured on a numeric rating scale ranging from 0 to 10. The primary efficacy analysis was the intention to treat (baseline observation carried forward). Secondary outcomes included a per protocol analysis and effects on spasticity, evoked pain, sleep problems, anxiety, depression, and global impression of change. We randomized 73 individuals with neuropathic pain due to SCI, of which 5 had a major protocol violation, and thus 68 were included in the primary analysis. There was no difference in mean pain intensity between PEA-um and placebo treatment (P = 0.46, mean reductions in pain scores 0.4 (-0.1 to 0.9) vs 0.7 (0.2-1.2); difference of means 0.3 (-0.4 to 0.9)). There was also no effect of PEA-um as add-on therapy on spasticity, insomnia, or psychological functioning. PEA was not associated with more adverse effects than placebo. PMID:27227691

  16. Evolutionary considerations in the development of chronic pelvic pain.

    Science.gov (United States)

    Jarrell, John; Arendt-Nielsen, Lars

    2016-08-01

    Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. PMID:27269450

  17. Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial.

    Science.gov (United States)

    Berman, Jonathan S; Symonds, Catherine; Birch, Rolfe

    2004-12-01

    The objective was to investigate the effectiveness of cannabis-based medicines for treatment of chronic pain associated with brachial plexus root avulsion. This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury, pain descriptions and patient demographics. Forty-eight patients with at least one avulsed root and baseline pain score of four or more on an 11-point ordinate scale participated in a randomised, double-blind, placebo-controlled, three period crossover study. All patients had intractable symptoms regardless of current analgesic therapy. Patients entered a baseline period of 2 weeks, followed by three, 2-week treatment periods during each of which they received one of three oromucosal spray preparations. These were placebo and two whole plant extracts of Cannabis sativa L.: GW-1000-02 (Sativex), containing Delta(9)tetrahydrocannabinol (THC):cannabidiol (CBD) in an approximate 1:1 ratio and GW-2000-02, containing primarily THC. The primary outcome measure was the mean pain severity score during the last 7 days of treatment. Secondary outcome measures included pain related quality of life assessments. The primary outcome measure failed to fall by the two points defined in our hypothesis. However, both this measure and measures of sleep showed statistically significant improvements. The study medications were generally well tolerated with the majority of adverse events, including intoxication type reactions, being mild to moderate in severity and resolving spontaneously. Studies of longer duration in neuropathic pain are required to confirm a clinically relevant, improvement in the treatment of this condition. PMID:15561385

  18. Gene therapy for neuropathic pain by silencing of TNF-α expression with lentiviral vectors targeting the dorsal root ganglion in mice.

    Directory of Open Access Journals (Sweden)

    Nobuhiro Ogawa

    Full Text Available Neuropathic pain can be a debilitating condition. Many types of drugs that have been used to treat neuropathic pain have only limited efficacy. Recent studies indicate that pro-inflammatory mediators including tumor necrosis factor α (TNF-α are involved in the pathogenesis of neuropathic pain. In the present study, we engineered a gene therapy strategy to relieve neuropathic pain by silencing TNF-α expression in the dorsal root ganglion (DRG using lentiviral vectors expressing TNF short hairpin RNA1-4 (LV-TNF-shRNA1-4 in mice. First, based on its efficacy in silencing TNF-α in vitro, we selected shRNA3 to construct LV-TNF-shRNA3 for in vivo study. We used L5 spinal nerve transection (SNT mice as a neuropathic pain model. These animals were found to display up-regulated mRNA expression of activating transcription factor 3 (ATF3 and neuropeptide Y (NPY, injury markers, and interleukin (IL-6, an inflammatory cytokine in the ipsilateral L5 DRG. Injection of LV-TNF-shRNA3 onto the proximal transected site suppressed significantly the mRNA levels of ATF3, NPY and IL-6, reduced mechanical allodynia and neuronal cell death of DRG neurons. These results suggest that lentiviral-mediated silencing of TNF-α in DRG relieves neuropathic pain and reduces neuronal cell death, and may constitute a novel therapeutic option for neuropathic pain.

  19. CHRONIC PAIN AFTER INGUINAL HERNIA REPAIR

    Directory of Open Access Journals (Sweden)

    Suresh

    2014-09-01

    Full Text Available : BACKGROUND: Chronic post herniorrhaphy groin pain is defined as pain lasting > 6 months after surgery, which is one of the most important complication occurring after inguinal hernia repair, occurs with greater frequency than previously thought. Chronic groin pain is one of the most significant complications following inguinal hernia repair, and majority of chronic pain has been attributed to ilioinguinal nerve entrapment. Various other factors are involved in development of chronic pain. MATERIAL AND METHODS: Patients undergoing elective inguinal hernioplasty in Victoria hospital from November2011 to May 2013 were included in the study. A total of 227 patients met the inclusion criteria and were available for follow up at end of six months. A detailed preoperative, intraoperative and post-operative details of cases were recorded according to proforma. The postoperative pain and pain at two, seven days and at end of six months were recorded on a VAS scale. RESULTS: Chronic pain at six month follow up was present in 89 patients constituting 39.4% of all patients undergoing hernia repair. It was seen that 26.9% without preoperative pain developed chronic pain whereas 76.7 % of patients with preoperative pain developed chronic pain. Patients with significant preoperative pain had higher chances of developing chronic pain (p<.0001. Preemptive analgesia failed to show statistical significance in development of chronic pain (p=0.079. Nerve injury were present in 22 of cases it was found that nerve injury significantly affected development of chronic pain (p=0.001.Post-operative infiltration of local anesthesia was practiced in 16.3 % of cases and it was found that local infiltration at incision site significantly reduced incidence of chronic pain (p=0.001.Postoperative complications in the form of hematoma, seroma or infection was present in 8.5 % of cases. It was found that post-operative complication not only increased early post-operative pain

  20. Dural neurogenic inflammation induced by neuropathic pain is specific to cranial region.

    Science.gov (United States)

    Filipović, B; Matak, I; Lacković, Z

    2014-05-01

    Up to now, dural neurogenic inflammation (DNI) has been studied primarily as a part of migraine pain pathophysiology. A recent study from our laboratory demonstrated the occurrence of DNI in response to peripheral trigeminal nerve injury. In this report, we characterize the occurrence of DNI after different peripheral nerve injuries in and outside of the trigeminal region. We have used the infraorbital nerve constriction injury model (IoNC) as a model of trigeminal neuropathic pain. Greater occipital nerve constriction injury (GoNC), partial transection of the sciatic nerve (ScNT) and sciatic nerve constriction injury (SCI) were employed to characterize the occurrence of DNI in response to nerve injury outside of the trigeminal region. DNI was measured as colorimetric absorbance of Evans blue plasma protein complexes. In addition, cellular inflammatory response in dural tissue was histologically examined in IoNC and SCI models. In comparison to the strong DNI evoked by IoNC, a smaller but significant DNI has been observed following the GoNC. However, DNI has not been observed either in cranial or in lumbar dura following ScNT and SCI. Histological evidence has demonstrated a dural proinflammatory cell infiltration in the IoNC model, which is in contrast to the SCI model. Inflammatory cell types (lymphocytes, plasma cells, and monocytes) have indicated the presence of sterile cellular inflammatory response in the IoNC model. To our knowledge, this is the first observation that the DNI evoked by peripheral neuropathic pain is specific to the trigeminal area and the adjacent occipital area. DNI after peripheral nerve injury consists of both plasma protein extravasation and proinflammatory cell infiltration.

  1. Bilateral Sensory Abnormalities in Patients with Unilateral Neuropathic Pain; A Quantitative Sensory Testing (QST) Study

    NARCIS (Netherlands)

    Konopka, Karl-Heinz; Harbers, Marten; Houghton, Andrea; Kortekaas, Rudie; van Vliet, Andre; Timmerman, Wia; den Boer, Johan A.; Struys, Michel M. R. F.; van Wijhe, Marten

    2012-01-01

    In patients who experience unilateral chronic pain, abnormal sensory perception at the non-painful side has been reported. Contralateral sensory changes in these patients have been given little attention, possibly because they are regarded as clinically irrelevant. Still, bilateral sensory changes i

  2. Chronic pain and invasive therapy

    Directory of Open Access Journals (Sweden)

    Alessandro Rocco

    2009-05-01

    Full Text Available The chronic pain “three-step” OMS ladder is likely to be revised, in order to introduce a “fourth step” including clinical indications for the invasive analgesic procedures. The number of patients who undergo such procedures is likely to increase, as well as modern oncology and palliative medicine development. Most of invasive approaches include central (spinal neuromodulation and peripheral (gangliar neurolysis, percutaneous vertebral reduction techniques, as well as pharmacological (opioids and adiuvants, chemical (alcohol and physical (electrical stimulation, thermic neurolysis means. Rarely effective as unique therapies, invasive procedures have to be accurately patient-selected and considered supplementary to conservative approaches, in order to minimize the adverse events deriving from a long term opioid therapy. In the near future, the development of both pain science and biomedical technology will probably be accompanied by the improvement of the knowledge regarding the recourse to invasive analgesic procedures.

  3. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes.

    Directory of Open Access Journals (Sweden)

    Sara Marinelli

    Full Text Available In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25, the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A, could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw's nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC. We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients' quality of life.

  4. The Analgesic Effect on Neuropathic Pain of Retrogradely Transported botulinum Neurotoxin A Involves Schwann Cells and Astrocytes

    Science.gov (United States)

    Ricordy, Ruggero; Uggenti, Carolina; Tata, Ada Maria; Luvisetto, Siro; Pavone, Flaminia

    2012-01-01

    In recent years a growing debate is about whether botulinum neurotoxins are retrogradely transported from the site of injection. Immunodetection of cleaved SNAP-25 (cl-SNAP-25), the protein of the SNARE complex targeted by botulinum neurotoxin serotype A (BoNT/A), could represent an excellent approach to investigate the mechanism of action on the nociceptive pathways at peripheral and/or central level. After peripheral administration of BoNT/A, we analyzed the expression of cl-SNAP-25, from the hindpaw’s nerve endings to the spinal cord, together with the behavioral effects on neuropathic pain. We used the chronic constriction injury of the sciatic nerve in CD1 mice as animal model of neuropathic pain. We evaluated immunostaining of cl-SNAP-25 in the peripheral nerve endings, along the sciatic nerve, in dorsal root ganglia and in spinal dorsal horns after intraplantar injection of saline or BoNT/A, alone or colocalized with either glial fibrillar acidic protein, GFAP, or complement receptor 3/cluster of differentiation 11b, CD11b, or neuronal nuclei, NeuN, depending on the area investigated. Immunofluorescence analysis shows the presence of the cl-SNAP-25 in all tissues examined, from the peripheral endings to the spinal cord, suggesting a retrograde transport of BoNT/A. Moreover, we performed in vitro experiments to ascertain if BoNT/A was able to interact with the proliferative state of Schwann cells (SC). We found that BoNT/A modulates the proliferation of SC and inhibits the acetylcholine release from SC, evidencing a new biological effect of the toxin and further supporting the retrograde transport of the toxin along the nerve and its ability to influence regenerative processes. The present results strongly sustain a combinatorial action at peripheral and central neural levels and encourage the use of BoNT/A for the pathological pain conditions difficult to treat in clinical practice and dramatically impairing patients’ quality of life. PMID:23110146

  5. Protective Effect of Ethanol Extracts of Hericium erinaceus on Alloxan-Induced Diabetic Neuropathic Pain in Rats

    OpenAIRE

    Yi, Zhang; Shao-long, Yang; Ai-hong, Wang; Zhi-chun, Sun; Ya-fen, Zhuo; Ye-ting, Xu; Yu-ling, He

    2015-01-01

    We investigated the effects of Hericium erinaceus (HEE) on alloxan induced diabetic neuropathic pain in laboratory rats. Alloxan induced diabetic rats were administered orally HEE. After 6 weeks of treatments, treatment with HEE 40 mg/kg in diabetic animals showed significant increase in pain threshold and paw withdrawal threshold and significant decrease in serum glucose and urine glucose. We also observed a significant increase in lactate dehydrogenase (LDH), Lipid peroxidation (LPO), gluta...

  6. Concurrent Activation of the Somatosensory Forebrain and Deactivation of Periaqueductal Grey Associated With Diabetes-Induced Neuropathic Pain

    OpenAIRE

    Paulson, Pamela E.; Wiley, John W.; Morrow, Thomas J.

    2007-01-01

    We combined behavioral testing with brain imaging using 99mTc-HMPAO (Amersham Health), to identify CNS structures reflecting alterations in pain perception in the streptozotocin (STZ) model of Type 1 diabetes. We induced diabetic hyperglycemia (blood glucose >300 mg/dl) by injecting male Sprague-Dawley rats with STZ (45 mg/kg i.p.). Four weeks after STZ, diabetic rats exhibited behaviors indicative of neuropathic pain (hypersensitivity thermal stimuli) and this hypersensitivity persisted for ...

  7. Mindfulness, acceptance and catastrophizing in chronic pain.

    Directory of Open Access Journals (Sweden)

    Maaike J de Boer

    Full Text Available OBJECTIVES: Catastrophizing is often the primary target of the cognitive-behavioral treatment of chronic pain. Recent literature on acceptance and commitment therapy (ACT suggests an important role in the pain experience for the concepts mindfulness and acceptance. The aim of this study is to examine the influence of mindfulness and general psychological acceptance on pain-related catastrophizing in patients with chronic pain. METHODS: A cross-sectional survey was conducted, including 87 chronic pain patients from an academic outpatient pain center. RESULTS: The results show that general psychological acceptance (measured with the AAQ-II is a strong predictor of pain-related catastrophizing, independent of gender, age and pain intensity. Mindfulness (measured with the MAAS did not predict levels of pain-related catastrophizing. DISCUSSION: Acceptance of psychological experiences outside of pain itself is related to catastrophizing. Thus, acceptance seems to play a role in the pain experience and should be part of the treatment of chronic pain. The focus of the ACT treatment of chronic pain does not necessarily have to be on acceptance of pain per se, but may be aimed at acceptance of unwanted experiences in general. Mindfulness in the sense of "acting with awareness" is however not related to catastrophizing. Based on our research findings in comparisons with those of other authors, we recommend a broader conceptualization of mindfulness and the use of a multifaceted questionnaire for mindfulness instead of the unidimensional MAAS.

  8. A streptozotocin-induced diabetic neuropathic pain model for static or dynamic mechanical allodynia and vulvodynia: validation using topical and systemic gabapentin.

    Science.gov (United States)

    Ali, Gowhar; Subhan, Fazal; Abbas, Muzaffar; Zeb, Jehan; Shahid, Muhammad; Sewell, Robert D E

    2015-11-01

    Neuropathic vulvodynia is a state of vulval discomfort characterized by a burning sensation, diffuse pain, pruritus or rawness with an acute or chronic onset. Diabetes mellitus may cause this type of vulvar pain in several ways, so this study was conducted to evaluate streptozotocin-induced diabetes as a neuropathic pain model for vulvodynia in female rats. The presence of streptozotocin (50 mg/kg i.p.)-induced diabetes was initially verified by disclosure of pancreatic tissue degeneration, blood glucose elevation and body weight loss 5-29 days after a single treatment. Dynamic (shortened paw withdrawal latency to light brushing) and static (diminished von Frey filament threshold pressure) mechanical allodynia was then confirmed on the plantar foot surface. Subsequently, both static and dynamic vulvodynia was detected by application of the paradigm to the vulval region. Systemic gabapentin (75 mg/kg, i.p.) and topical gabapentin (10 % gel) were finally tested against allodynia and vulvodynia. Topical gabapentin and the control gel vehicle significantly increased paw withdrawal threshold in the case of the static allodynia model and also paw withdrawal latency in the model for dynamic allodynia when compared with the streptozotocin-pretreated group. Likewise, in the case of static and dynamic vulvodynia, there was a significant antivulvodynia effect of systemic and topical gabapentin treatment. These outcomes substantiate the value of this model not only for allodynia but also for vulvodynia, and this was corroborated by the findings not only with systemic but also with topical gabapentin.

  9. The Edible Brown Seaweed Ecklonia cava Reduces Hypersensitivity in Postoperative and Neuropathic Pain Models in Rats

    Directory of Open Access Journals (Sweden)

    Jae Goo Kim

    2014-06-01

    Full Text Available The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05. Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats.

  10. The burden of chronic pain

    DEFF Research Database (Denmark)

    Kurita, Geana Paula; Sjøgren, Per; Juel, Knud;

    2012-01-01

    in the adult Danish population and to analyze associated factors such as diseases, immigration, and opioid use. This cross-sectional survey combines individual-based information from the Danish Health Survey (2010) and official Danish health and socioeconomic, individual-based registers. The simple random...... sample consisted of 25,000 individuals (≥16 years old) living in Denmark. In all, 60.7% completed a mailed or online questionnaire. Associations were examined with multiple logistic regression analysis. The study population consisted of 14,925 individuals in whom a high prevalence of chronic pain (26...

  11. Chronic pain after open inguinal hernia repair.

    Science.gov (United States)

    Nikkolo, Ceith; Lepner, Urmas

    2016-01-01

    Following the widespread use of mesh repairs, recurrence rates after inguinal hernia surgery have become acceptable and focus has shifted from recurrence to chronic pain. Although pain can be controlled with analgesics, chronic postsurgical pain is a major clinical problem, which can significantly influence the patient's quality of life. The rate of chronic pain after inguinal hernia mesh repair can reach 51.6%. The reasons for posthernioplasty chronic pain are often unclear. It has been linked to nerve injury and nerve entrapment, but there is also association between the rate of chronic pain and the type of mesh used for hernia repair. As there are >160 meshes available in the market, it is difficult to choose a mesh whose usage would result in the best outcome. Different mesh characteristics have been studied, among them weight of mesh has probably gained the most attention. The choice of adequate therapy for chronic groin pain after inguinal hernia repair is controversial. The European Hernia Society recommends that a multidisciplinary approach at a pain clinic should be considered for the treatment of chronic postoperative pain. Although surgical treatment of chronic posthernioplasty pain is limited because of the lack of relevant research data, resection of entrapped nerves, mesh removal in the case of mesh related pain or removal of fixation sutures can be beneficial for the patient with severe pain after inguinal hernia surgery. One drawback of published studies is the lack of consensus over definition of chronic pain, which makes it complicated to compare the results of different studies and to conduct meta-analyses and systematic reviews. Therefore, a uniform definition of chronic pain and its best assessment methods should be developed in order to conduct top quality multicenter randomized trials. Further research to develop meshes with optimal parameters is of vital importance and should be encouraged. PMID:26567717

  12. Ehlers-Danlos syndrome and chronic pain.

    Science.gov (United States)

    Hsu, Lanny

    2012-06-01

    Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are Ehlers-Danlos syndrome and associated chronic pain; the information is meant to help readers understand the mechanisms for pain in this connective tissue disorder as well as general treatment principles for chronic pain management. PMID:22616833

  13. Chronic Pain Syndromes and Borderline Personality

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2012-01-01

    The assessment and management of chronic pain is challenging and, according to the existing literature, oftentimes associated with various forms of psychopathology, including borderline personality disorder. Since 1994, eight studies have explored the relationship between chronic pain syndromes and borderline personality disorder. In averaging the prevalence rates in these studies, 30 percent of participants with chronic pain harbor this Axis II disorder. Related studies suggest that individu...

  14. FEATURES OF THE CHRONIC PAIN SYNDROME IN PATIENTS WITH RHEUMATOID ARTHRITIS AND MEDICAL DIAGNOSTIC TACTICS

    Directory of Open Access Journals (Sweden)

    M. A. Gromova

    2016-01-01

    Full Text Available Objective: to establish features of a chronic pain syndrome disorders in patients with rheumatoid arthritis, to reveal correlation with psychoemotional disorders and to develop the differential approach to maintaining patients. Materials and methods. 101 patients at the age of 60.6 ± 11.8 years, 92 % of women, with reliable rheumatoid arthritis (American College of Rheumatology – ACR, 1987, were examined. The visual analog scale was used for an assessment of pain strength at the moment; the Van Korff’s questionnaire – for determination of pain strength at the moment and retrospectively for the last half a year with an assessment of disadaptation level and disability, ranging of a chronic pain syndrome on classes; the McGill Pain Questionnaire – for the characteristic of touchsensitive and emotional components of pain. Neuropathic pain was revealed by DN4 questionnaire. Anxiety and depression were determined by the Hospital Anxiety and Depression Scale (HADS. Fibromyalgia diagnosed by criteria of ACR, (1990. Results. Pain estimated by various scales and questionnaires varied from moderated to intensive. According to Van Korff’s questionnaire it was characterized by average level of disadaptation and easy disability that corresponded to the second class of chronic pain. The Rank pain index of the McGill Pain Questionnaire touch scale testified that pain was described by a smaller number of definitions on a touch scale than on emotional. This indicates a moderate impact of pain syndrome on a state of mind. Neuropathic pain is diagnosed for 37.3 % of patients with tunnel syndrome, mononeuritis and touch polyneuropathy. The secondary fibromyalgia is revealed for 2 % of patients with early rheumatoid arthritis of high activity. According to HADS anxiety and depression was revealed for 58 and 59 % of patients correspondingly. This demanded psychotherapeutic consultation and additional correction. We proposed the algorithm of diagnostic and

  15. Review of posttraumatic stress disorder and chronic pain: The path to integrated care

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    Carri-Ann Gibson, MD, DAAPM

    2012-06-01

    Full Text Available With the large number of Veterans experiencing posttraumatic stress disorder (PTSD and chronic pain, the purpose of this article is to review the prevalence of PTSD and chronic pain, the theoretical models that explain the maintenance of both conditions, and the challenges faced by providers and families who care for these patients. The Department of Veterans Affairs (VA/Department of Defense (DOD VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress with special attention to chronic pain is presented. Limited scientific evidence supports specific care and treatment of PTSD and chronic pain, and this challenges providers to investigate and research potential treatment options. Integrated care models designed for working with these patients are reviewed, including a focus on the techniques and strategies to address not only PTSD and chronic pain, but other conditions, including substance dependence and depression. A specific focus on headaches, back pain, and neuropathic pain follows, including treatment recommendations such as pharmacological, psychotherapeutic, and complementary approaches, given the high rates of these pain complaints for Veterans in PTSD clinical programs. Integrated care is presented as a viable solution and approach that challenges clinicians and researchers to develop innovative, scientifically based therapeutics and treatments to enhance the recovery and quality of life for Veterans with PTSD and chronic pain.

  16. PSD95 Gene Specific siRNAs Attenuate Neuropathic Pain through Modulating Neuron Sensibility and Postsynaptic CaMKⅡα Phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Le Shen; Xu Li; Nen Chen; Li Xu; Wei Liu; Xue-rong Yu; Yu-guang Huang

    2011-01-01

    Objective To observe the effects of PSD95 gene specific siRNAs on neuropathic pain relief,neuron viability,and postsynaptic calcium/calmodulin-dependent protein kinase Ⅱα (CaMKⅡα) phosphorylation in vitro and in vivo.Methods Gene-specific siRNAs of rat PSD95 were synthesized chemically for transfection.Adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups:naive group (n=6),sham group (n=6),and sciatic nerve chronic constriction injury (CCI) group (n=24).The CCI group was further divided into 4 groups (n=6 in each group),which were pretreated with normal saline,transfection vehicle,negative control siRNAs,and PSD95 gene specific siRNAs respectively.All the subgroups received corresponding agents intrathecally for 3 days,started one day before the CCI of sciatic nerve.Both mechanical allodynia and thermal hyperalgesia were measured on post-operative day 3 and 7.PSD95 gene silenced NG108-15 cells were further stimulated by glutamate,with the cell viability and the expression/phosphorylation of CaMKⅡα measured by MTT cell proliferation assay andWestern blot,respectively.Results The siRNAs decreased PSD95 mRNA level significantly both in vivo and in vitro.Neuropathic pain rats pretreated with PSD95 gene specific siRNAs exhibited significant elevation in the mechanical withdrawal threshold and paw withdrawal thermal latency,without affecting the baseline nociception.PSD95 gene silencing enhanced neuronal tolerance against the glutamate excitotoxicity,meanwhile the phosphorylation of CaMKⅡαThr286 was attenuated.Conclusion Pre-emptive administration of PSD95 gene specific siRNAs may attenuate the central sensitization CaMKⅡα-related signaling cascades,leading to the relief of neuropathic pain.

  17. Electronic momentary assessment in chronic pain (I): pain and psychological pain responses as predictors of pain intensity.

    OpenAIRE

    Sorbi, M.J.; Peters, M.L.; Kruise, D.A.; Maas, C.J.M.; Kerssens, J. J.; Verhaak, P.F.M.; Bensing, J M

    2006-01-01

    Objectives and Methods: Electronic momentary assessment was employed to substantiate the relevance of psychological functioning in chronic pain. More than 7100 electronic diaries from 80 patients with varying IASP classified types of chronic pain served to investigate to what extent fear-avoidance, cognitive and spousal solicitous and punishing pain responses explained fluctuations in pain intensity and whether patients with pre-chronic, recently chronic and persistently chronic pain differed...

  18. Lipid- and sugar-modified endomorphins: Novel targets for the treatment of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Pegah eVaramini

    2013-12-01

    Full Text Available Endomorphins are endogenous opioid peptides that cause potent antinociception in rodent models of acute and neuropathic pain with less undesirable side effects than opioid alkaloids. However, endomorphins are poorly suited to clinical applications because of low membrane permeability and a susceptibility to enzymatic degradation. Glycosylation and lipidation have proven to be two of the most robust approaches for the generation of new therapeutic endomorphin derivatives. Conjugation with lipoamino acids (LAA confers an amphipathic character to the peptide, which improved interaction between the peptide and the lipid bilayer of the cell membranes, increasing permeability. Glycosylation can also improve peptide stability and blood brain barrier (BBB transport. It is believed that an endocytotic mechanism (transcytosis is responsible for the systemic delivery of water-soluble glycopeptides. This review discusses the application of glycosylation and lipidation strategies to improve the drug-like properties of endomorphins. Pharmacologically active endomorphin analogues with less adverse effects are also discussed.

  19. Neuropathic pain phenotyping by international consensus (NeuroPPIC) for genetic studies: a NeuPSIG systematic review, Delphi survey, and expert panel recommendations

    Science.gov (United States)

    van Hecke, Oliver; Kamerman, Peter R.; Attal, Nadine; Baron, Ralf; Bjornsdottir, Gyda; Bennett, David L.H.; Bennett, Michael I.; Bouhassira, Didier; Diatchenko, Luda; Freeman, Roy; Freynhagen, Rainer; Haanpää, Maija; Jensen, Troels S.; Raja, Srinivasa N.; Rice, Andrew S.C.; Seltzer, Ze'ev; Thorgeirsson, Thorgeir E.; Yarnitsky, David; Smith, Blair H.

    2015-01-01

    Abstract For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in part because of differences in phenotypes used for case ascertainment. Because there is no consensus on the nature of these phenotypes, nor on the methods of collecting them, this study aimed to provide guidelines on collecting and reporting phenotypes in cases and controls for genetic studies. Consensus was achieved through a staged approach: (1) systematic literature review to identify all neuropathic pain phenotypes used in previous genetic studies; (2) Delphi survey to identify the most useful neuropathic pain phenotypes and their validity and feasibility; and (3) meeting of experts to reach consensus on the optimal phenotype(s) to be collected from patients with neuropathic pain for genetic studies. A basic “entry level” set of phenotypes was identified for any genetic study of neuropathic pain. This set identifies cases of “possible” neuropathic pain, and controls, and includes: (1) a validated symptom-based questionnaire to determine whether any pain is likely to be ne