Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain

Treatment of neuropathic pain, triggered by multiple insults to the nervous system, is a clinical challenge because the underlying mechanisms of neuropathic pain development remain poorly understood. Most treatments do not differentiate between different phases of neuropathic pain pathophysiology and simply focus on blocking neurotransmission, producing transient pain relief. Here, we report that early- and late-phase neuropathic pain development in rats and mice after nerve injury require different matrix metalloproteinases (MMPs). After spinal nerve ligation, MMP-9 shows a rapid and transient upregulation in injured dorsal root ganglion (DRG) primary sensory neurons consistent with an early phase of neuropathic pain, whereas MMP-2 shows a delayed response in DRG satellite cells and spinal astrocytes consistent with a late phase of neuropathic pain. Local inhibition of MMP-9 by an intrathecal route inhibits the early phase of neuropathic pain, whereas inhibition of MMP-2 suppresses the late phase of neuropathic pain. Further, intrathecal administration of MMP-9 or MMP-2 is sufficient to produce neuropathic pain symptoms. After nerve injury, MMP-9 induces neuropathic pain through interleukin-1beta cleavage and microglial activation at early times, whereas MMP-2 maintains neuropathic pain through interleukin-1beta cleavage and astrocyte activation at later times. Inhibition of MMP may provide a novel therapeutic approach for the treatment of neuropathic pain at different phases.     

Prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano

The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly.     

T型钙通道在神经病理性痛模型中介导疼痛的研究进展

神经病理痛是临床上常见病症,其发病机制尚不清楚,目前尚无有效的治疗手段,其慢性神经病理痛持续时间长,故其研究成为疼痛领域的热点和重点。近年来发现T型钙通道在神经病理性疼痛中起到了关键性的作用。本文将近年T型钙通道在神经病理性痛模型中介导疼痛的机制研究进展加以综述。     

Somatosensory profiles but not numbers of somatosensory abnormalities of neuropathic pain patients correspond with neuropathic pain grading

Due to the lack of a specific diagnostic tool for neuropathic pain, a grading system to categorize pain as 'definite', 'probable', 'possible' and 'unlikely' neuropathic was proposed. Somatosensory abnormalities are common in neuropathic pain and it has been suggested that a greater number of abnormalities would be present in patients with 'probable' and 'definite' grades. To test this hypothesis, we investigated the presence of somatosensory abnormalities by means of Quantitative Sensory Testing (QST) in patients with a clinical diagnosis of neuropathic pain and correlated the number of sensory abnormalities and sensory profiles to the different grades. Of patients who were clinically diagnosed with neuropathic pain, only 60% were graded as 'definite' or 'probable', while 40% were graded as 'possible' or 'unlikely' neuropathic pain. Apparently, there is a mismatch between a clinical neuropathic pain diagnosis and neuropathic pain grading. Contrary to the expectation, patients with 'probable' and 'definite' grades did not have a greater number of abnormalities. Instead, similar numbers of somatosensory abnormalities were identified for each grade. The profiles of sensory signs in 'definite' and 'probable' neuropathic pain were not significantly different, but different from the 'unlikely' grade. This latter difference could be attributed to differences in the prevalence of patients with a mixture of sensory gain and loss and with sensory loss only. The grading system allows a separation of neuropathic and non-neuropathic pain based on profiles but not on the total number of sensory abnormalities. Our findings indicate that patient selection based on grading of neuropathic pain may provide advantages in selecting homogenous groups for clinical research.     

miR-194 relieve neuropathic pain and prevent neuroinflammation via targeting FOXA1

The emerging role of microRNAs (miRNAs) have been deeply explored in multiple diseases including neuropathic pain. miR-194 was widely reported to be a tumor suppressor and was related to the inflammatory response. The critical role of neuroinflammation on neuropathic pain leads to a thinking about the relationship between miR-194 and neuropathic pain. However, the function of miR-194 in neuropathic pain remains unknown. This study was aimed to explore the relationship between miR-194 and neuropathic pain progression by chronic sciatic nerve injury (CCI). miR-194 abnormally downregulated in the CCI model rat and its overexpression significantly alleviates neuroinflammation in vivo. We predict Forkhead box protein A1 (FOXA1) as a direct target of miR-194, whose restoration can markedly reverse the effects of miR-194 on neuropathic pain. Overall, our study demonstrated a novel mechanism of neuropathic pain progression that miR-194 alleviates neuropathic pain via targeting FOXA1 and preventing neuroinflammation by downregulating inflammatory cytokines containing cyclooxygenase 2, interleukin 6 (IL-6), and IL-10 in vivo, which can be reversed by the overexpression of FOXA1.     

Platelet-Rich Plasma and the Elimination of Neuropathic Pain

Peripheral neuropathic pain typically results from trauma-induced nociceptive neuron hyperexcitability and their spontaneous ectopic activity. This pain persists until the trauma-induced cascade of events runs its full course, which results in complete tissue repair, including the nociceptive neurons recovering their normal biophysical properties, ceasing to be hyperexcitable, and stopping having spontaneous electrical activity. However, if a wound undergoes no, insufficient, or too much inflammation, or if a wound becomes stuck in an inflammatory state, chronic neuropathic pain persists. Although various drugs and techniques provide temporary relief from chronic neuropathic pain, many have serious side effects, are not effective, none promotes the completion of the wound healing process, and none provides permanent pain relief. This paper examines the hypothesis that chronic neuropathic pain can be permanently eliminated by applying platelet-rich plasma to the site at which the pain originates, thereby triggering the complete cascade of events involved in normal wound repair. Many published papers claim that the clinical application of platelet-rich plasma to painful sites, such as muscle injuries and joints, or to the ends of nerves evoking chronic neuropathic pain, a process often referred to as prolotherapy, eliminates pain initiated at such sites. However, there is no published explanation of a possible mechanism/s by which platelet-rich plasma may accomplish this effect. This paper discusses the normal physiological cascade of trauma-induced events that lead to chronic neuropathic pain and its eventual elimination, techniques being studied to reduce or eliminate neuropathic pain, and how the application of platelet-rich plasma may lead to the permanent elimination of neuropathic pain. It concludes that platelet-rich plasma eliminates neuropathic pain primarily by platelet- and stem cell-released factors initiating the complex cascade of wound healing events, starting with the induction of enhanced inflammation and its complete resolution, followed by all the subsequent steps of tissue remodeling, wound repair and axon regeneration that result in the elimination of neuropathic pain, and also by some of these same factors acting directly on neurons to promote axon regeneration thereby eliminating neuropathic pain.     

Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial

Background

Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.

Methods

We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.

Results

Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.

Conclusions

The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.     

MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1

MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K⁺ channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.     

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

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.     

Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis

IntroductionIncreasing evidence indicates that features suggestive of neuropathic pain may also be present in patients with common rheumatic conditions. The objective of this study was to examine neuropathic-like pain symptoms and associated factors in patients with rheumatoid arthritis.MethodsWe used the painDETECT screening tool to identify possible or likely neuropathic pain in 159 outpatients with rheumatoid arthritis. Patients additionally completed other self-reported measures, while clinical measures were assessed to calculate the 28-joint Disease Activity Score. Univariate analyses and multivariable logistic regression were used to identify factors associated with neuropathic pain features.ResultsAccording to the painDETECT, 27 patients (17.0 %) were classified as having likely neuropathic pain and 34 patients (21.4 %) as having possible neuropathic pain. Besides reporting more severe pain, patients with likely or possible neuropathic pain were more likely to meet the diagnostic criteria for fibromyalgia, to use analgesics, and to have more tender joints and a worse physical and mental health status as measured by the 36-item Short-Form health survey. In multivariable analysis, physical (P < 0.001) and mental health status (P = 0.006) remained significantly associated with neuropathic pain features, even after controlling for pain severity.ConclusionsThese findings suggest that a sizeable proportion of patients with relatively well-controlled rheumatoid arthritis report symptoms suggestive of neuropathic pain. Neuropathic-like pain symptoms are independently associated with worse self-reported physical and mental health.     

胸外科手术术后神经病理性疼痛的发生情况及相关因素分析

目的:探讨胸外科手术术后神经病理性疼痛的发生情况及相关危险因素。方法:回顾性分析2015年至2016年就诊于我院行胸外科手术的患者的临床资料,包括患者的年龄、性别、吸烟史、BMI、术前是否使用催眠药物、术前诊断、手术侧别、手术方式、是否为微创、硬膜外自控镇痛泵使用情况、术中失血量、手术持续时间、引流管引流时间及是否发生神经病理性疼痛,对比分析是否发生神经病理性疼痛患者的临床资料,对有差异的临床资料进行多因素Logistic回归分析探讨发生神经病理性疼痛的危险因素。结果:共有123例患者纳入研究,33例(26.8%)患者的患者术后出现神经病理性疼痛,6例(4.9%)患者在术后一年仍有持续性神经性病理疼痛,术后出现神经病理性疼痛的平均时间为术后第7天,平均持续时间为75天,发生神经病理性疼痛的患者吸烟比例(81.8%)、术前使用催眠药比例(57.6%)、开胸手术比例(81.8%)、术中失血量(185 mL)、手术时间(196分钟)、术后引流时间(2.5天)均高于没有发生神经病理性疼痛的患者。多因素分析显示术前使用催眠药(OR=2.322,P<0.001)、手术时间延长(OR=3.703,P<0.001)和术后引流时间延长(OR=2.675,P=0.002)均是神经病理性疼痛发生的危险因素,电视辅助胸腔镜手术方式是保护性因素(OR=0.453,P=0.002)。结论:术前使用催眠药物、延长的手术时间及术后引流时间增加了神经病理性疼痛发生的风险,电视辅助胸腔镜技术可减少其发生率。     

Proteomic analysis of differential protein expression in neuropathic pain and electroacupuncture treatment models

Acupuncture has long been used for pain relief. Although recent studies have shown that acupuncture can reduce neuropathic pain, the mechanism of this effect is not clear and little information is available regarding proteins that are involved in the development of neuropathic pain and the effects of acupuncture. We have developed an animal model for neuropathic pain using young adult male Sprague-Dawley rats. The model was confirmed by behavioral tests. Electroacupuncture (EA) treatment was applied to Zusanli (ST36) of neuropathic pain model to examine the analgesic effect of EA. The protein expression profile of the hypothalamus in both neuropathic pain and EA treatment models was analyzed using two-dimensional electrophoresis-based proteomics. We detected thirty-six proteins that were differentially expressed in the neuropathic pain model compared with normal rats and that restored to normal expression levels after EA treatment. Twenty-one of these proteins were identified in the MS-FiT database and are involved in a number of biological processes, including inflammation, enzyme metabolism and signal transduction. Potential applications of our results include the identification and characterization of signaling pathways involved in EA treatment and further exploration of the role of selected identified proteins in the animal model.     

miR-124-3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2

Emerging evidence has suggested that microRNAs play a critical role in neuropathic pain development. However, the biological role of miRNAs in regulating neuropathic pain remains barely known. In our present study, we found that miR-124-3p was significantly downregulated in rats after chronic sciatic nerve injury (CCI). In addition, it was showed that overexpression of miR-124-3p obviously repressed mechanical allodynia and heat hyperalgesia. Meanwhile, it has been reported that neuroinflammation can contribute a lot to neuropathic pain progression. Here, we found that inflammatory cytokine (IL-6, IL-1β, and TNF-⍺) protein expression in rats after CCI greatly increased and miR-124-3p mimics depressed inflammation cytokine levels. Consistently, miR-124-3p alleviated inflammation production in lipopolysaccharide-incubated spinal microglial cells. Bioinformatics analysis revealed that EZH2 acted as a direct target of miR-124-3p, which participated in the miR-124-3p-modulated effects on neuropathic pain development and neuroinflammation. We observed that miR-124-3p was able to promote neuroinflammation and neuropathic pain through targeting EZH2. The direct correlation between them was validated in our current study using dual-luciferase reporter assays. Subsequently, it was manifested that EZH2 abrogated the inhibitory role of miR-124-3p on neuropathic pain progression in CCI rats. Taken these together, our findings highlighted a novel contribution of miR-124-3p to neuropathic pain and indicated the possibilities for developing novel therapeutic options for neuropathic pain.     

Knockdown of Linc00052 alleviated spinal nerve ligation-triggered neuropathic pain through regulating miR-448 and JAK1

The dysfunction of the nervous system contributes to neuropathic pain. Long noncoding RNAs are reported to participate in neuropathic pain. Recently, Linc00052 is implicated to be closely associated with multiple diseases. Nevertheless, the mechanisms of Linc00052 remain barely explored in neuropathic pain development. Currently, spinal nerve ligation (SNL) triggered neuropathic pain was employed in our investigation. Here, we assessed the function of Linc00052 in SNL rat models. Interestingly, we reported Linc00052 was significantly elevated in SNL rats. Loss of Linc00052 could reduce neuropathic pain progression via regulating the behaviors of neuropathic pain. Additionally, knockdown of Linc00052 repressed the processes of neuroinflammation. Interleukin (IL)-6 and tumor necrosis factor α level were inhibited while IL-10 was induced by the silence of Linc00052. Moreover, we predicted miR-448 can serve as a target of Linc00052. miR-448 exerts a crucial power in several diseases. Currently, we exhibited miR-448 was remarkably downregulated in SNL rats. RNA immunoprecipitation experiments validated the association between miR-448 and Linc00052. Inhibition of Linc00052 could reverse the roles of miR-448 on neuropathic pain development. Furthermore, Janus kinase 1 (JAK1) was displayed as the putative target of miR-448 in the present investigation. It was showed that JAK1 was induced in SNL rats. Loss of miR-448 could dramatically induce the expression of JAK1, which was rescued by knockdown of Linc00052. Taken these together, our study implied that Linc00052 functioned as a novel target of neuropathic pain via sponging miR-448 and regulating JAK1.     

Early Repeated Administration of CXCR4 Antagonist AMD3100 Dose-Dependently Improves Neuropathic Pain in Rats After L5 Spinal Nerve Ligation

AMD3100 is a specific C-X-C chemokine receptor type 4 (CXCR4) antagonist which blocks the interaction between CXCR4 and CXCL12. Multiple lines of evidence suggest that AMD3100 has analgesic effects on many pathological pain states, including peripheral neuropathic pain. However, little is known about the underlying mechanisms. In the current study, we investigated the effect of different doses of AMD3100 on neuropathic pain in rats after L5 spinal nerve ligation. We used naloxone methiodide (NLXM) to further determine whether AMD3100-mediated analgesic effect was opioid-dependent. Behavioral study showed that early repeated administration of AMD3100 (2 and 5 mg/kg, i.p.) dose-dependently alleviates peripheral neuropathic pain. Flow cytometry, immunofluorescence and NLXM experiments showed that AMD3100 alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. Furthermore, we found that pro-inflammatory cytokines were down-regulated by AMD3100 using Enzyme-linked Immunosorbent Assay. Our data indicate that AMD3100 dose-dependently alleviates neuropathic pain partially by augmenting leukocyte-derived endogenous opioid secretion. This finding suggests that AMD3100 may be a viable pharmacotherapeutic strategy for the treatment of neuropathic pain.     

Constitutive GABA expression via a recombinant adeno-associated virus consistently attenuates neuropathic pain

Peripheral neuropathic pain is a common clinical problem with few existing treatments. Previously, we constructed rAAV bearing GAD65 and demonstrated that GAD65 and GABA can be constitutively produced in the CNS. To investigate the beneficial effects of GAD65 produced by rAAV and resulting GABA release in peripheral neuropathic pain, we established a neuropathic pain rat model. The direct administration of rAAV-GAD65 to dorsal root ganglion induced constitutive GAD65 expression, which was readily detected by immunohistochemistry. Both allodynic and hyperalgeic behavior tests suggested that neuropathic pain was noticeably reduced, along with the transgenic GAD65 expression. Moreover, the magnitude of pain relief was maintained during the entire experimental period. Concomitantly, the significant enhancement in GABA release following transgenic GAD65 expression was identified in vivo. Taken all together, these results provide evidence that persistent GAD65 and subsequent GABA expression in DRGs via rAAV effectively attenuates peripheral neuropathic pain for long period of time.     

Retracted: MicroRNA-217 relieved neuropathic pain through targeting toll-like receptor 5 expression

Neuropathic pain is the most common chronic pain that is caused by nerve injury or disease that influences the nervous system. Increasing evidence suggested that microRNAs (miRNAs) play a crucial role in neuropathic pain and neuroinflammation development. However, the functional role of miR-217 in the development of neuropathic pain remains unknown. In this study, we used rats to establish a neuropathic pain model and showed that the miR-217 expression level was upregulated in the spinal dorsal horn of bilateral sciatic nerve chronic constriction injury (bCCI). However, the expression of miR-217 was not changed in the anterior cingulated cortex (ACC), hippocampus, and dorsal root ganglion (DRG) of bCCI rats. Ectopic expression of miR-217 attenuated neuropathic pain and suppressed neuroinflammation expression in vivo. We identified toll-like receptor 5 (TLR5) as a direct target gene of miR-217 in the PC12 cell. In addition, we demonstrated that the expression level of TLR5 was upregulated in bCCI rats. Moreover, restoration of TLR5 rescued the inhibitory roles induced by miR-217 overexpression on neuropathic pain and neuroinflammation development. These data suggested that miR-217 played a pivotal role in the development of neuropathic pain partly through regulating TLR5 expression.     

Overexpression of miR-98 attenuates neuropathic pain development via targeting STAT3 in CCI rat models

MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR-98 has been reported to be involved in various diseases. However, little is known about the role of miR-98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR-98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR-98 was downregulated in CCI rat models. Overexpression of miR-9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR-98 and the direct correlation was confirmed. Then, miR-98 was overexpressed in CCI rats and it was found that miR-98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) expression was obviously induced in CCI rats, while miR-98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR-98 on neuropathic pain development. Taken these together, we reported that overexpression of miR-98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.     

Sensory function above lesion level in spinal cord injury patients with and without pain

Patients with spinal cord injury (SCI) may or may not develop central neuropathic pain despite having cord lesions of apparently the same site, extension and nature. The consequences of the cord lesion in the central nervous system and the mechanisms underlying pain are unclear. In this study, we examined sensory detection and pain thresholds above injury level in 17 SCI patients with central neuropathic pain, in 18 SCI patients without neuropathic pain, and in 20 control subjects without injury and pain. The SCI pain group had significantly higher cold and warm detection thresholds compared with the SCI pain free group and controls and higher tactile detection thresholds compared with the SCI pain free group. No difference in pain or pain tolerance thresholds was seen among pain and pain free SCI patients. These data suggest changes in somatosensory function in dermatomes rostral to the segmental injury level linked to the presence of central neuropathic pain in SCI patients. The results are discussed in relation to current concepts of pain inhibitory and facilitating systems.     

Sensory function above lesion level in spinal cord injury patients with and without pain

Patients with spinal cord injury (SCI) may or may not develop central neuropathic pain despite having cord lesions of apparently the same site, extension and nature. The consequences of the cord lesion in the central nervous system and the mechanisms underlying pain are unclear. In this study, we examined sensory detection and pain thresholds above injury level in 17 SCI patients with central neuropathic pain, in 18 SCI patients without neuropathic pain, and in 20 control subjects without injury and pain. The SCI pain group had significantly higher cold and warm detection thresholds compared with the SCI pain free group and controls and higher tactile detection thresholds compared with the SCI pain free group. No difference in pain or pain tolerance thresholds was seen among pain and pain free SCI patients. These data suggest changes in somatosensory function in dermatomes rostral to the segmental injury level linked to the presence of central neuropathic pain in SCI patients. The results are discussed in relation to current concepts of pain inhibitory and facilitating systems.