Spinal Cord Injury Neuropathic Pain Research Articles

Prevalence of Spasticity and Below-Level Neuropathic Pain Related to Spinal Cord Injury Level and Damage to the Lower Spinal Segments.

ObjectiveTo evaluate spasticity and below-level spinal cord injury neuropathic pain after spinal cord injury in patients with, or without, damage to the lumbar spinal cord and roots.Design/patientsChart review of 269 patients with spinal cord injury from segments C1 to T11.MethodsPatients were interviewed concerning leg spasticity and below-level spinal cord injury neuropathic pain in the lower trunk and legs. Damage to the lumbar spinal cord and roots was inferred where there was radiological evidence of a vertebral fracture, spinal stenosis or the narrowing of spinal foramina of a vertebra from thoracic 11 to lumbar 5, or; magnetic resonance imaging showing evidence of damage to the lumbar spinal cord and roots.ResultsAmong 161 patients without damage to the lumbar spinal cord and roots, 87% of those with cervical spinal cord injury experienced spasticity, compared with 85% with thoracic spinal cord injury. The corresponding figures for patients in whom damage to the lumbar spinal cord and roots was present were 57% and 52%, respectively. Below-level spinal cord injury neuropathic pain was not associated with damage to the lumbar spinal cord and roots. In those patients with no damage to the lumbar spinal cord and roots, regression showed that neither outcome was significantly associated with the level of spinal cord injury.ConclusionThe lack of segmental dependency for spinal cord injury and spasticity suggests mechanisms restricted mainly to the lumbar spinal cord. For below-level spinal cord injury neuropathic pain, additional mechanisms, other than lesions of the spino-thalamic tract, must be considered.LAY ABSTRACTFollowing a spinal cord injury, symptoms of increased nerve cell activity in the central nervous system appear, e.g. involuntary muscle activity (spasticity), below level neuropathic pain and urinary leakage. The distribution of overactive neurons is still unresolved. This chart review showed that leg spasticity was more frequent in patients with a cervical or thoracic spinal cord injury if the patients had no signs of damage to the lumbar spinal cord and roots. The occurrence of leg spasticity and below level spinal cord injury neuropathic pain was unrelated to each other or to the level of the spinal cord injury. This suggests that the mechanisms behind leg spasticity are mainly restricted to the lumbar spinal cord. For this pain, additional mechanisms other than lesions of the spino-thalamic tract must be considered

Dopamine D1 and D3 receptor modulators restore morphine analgesia and prevent opioid preference in a model of neuropathic pain

A secondary consequence of spinal cord injury (SCI) is debilitating chronic neuropathic pain, which is commonly morphine resistant and inadequately managed by current treatment options. Consequently, new pain management therapies are desperately needed. We previously reported that dopamine D3 receptor (D3R) dysfunction was associated with opioid resistance and increases in D1 receptor (D1R) protein expression in the spinal cord. Here, we demonstrate that in a model of SCI neuropathic pain, adjuvant therapy with a D3R agonist (pramipexole) or D1R antagonist (SCH 39166) can restore the analgesic effects of morphine and reduce reward potential. Prior to surgery thermal and mechanical thresholds were tested in three groups of female rats (naïve, sham, SCI). After surgery, testing was repeated under the following drug conditions: 1) saline, 2) morphine, 3) pramipexole, 4) SCH 39166, 5) morphine + pramipexole, and 6) morphine + SCH 39166. Reward potential of morphine and both combinations was assessed using conditioned place preference. Following SCI, morphine + pramipexole and morphine + SCH 39166 significantly increased both thermal and mechanical thresholds. Morphine alone induced conditioned place preference, but when combined with either the D3R agonist or D1R antagonist preference was not induced. The data suggest that adjunct therapy with receptor-specific dopamine modulators can restore morphine analgesia and decrease reward potential and thus, represents a new target for pain management therapy after SCI.

Pain assessment in hospitalized spinal cord injured patients - a controlled cross-sectional study.

Background and aims Following spinal cord injury (SCI), a majority of individuals may develop neuropathic pain, which further reduces quality of life. Pain is difficult to treat by medication; in fact, medication overuse may aggravate neuropathic pain in SCI by causing central sensitization (CS): a mechanism of hyper-reactivity of the dorsal horn neurons in the spinal cord with amplified cerebral pain response. The purpose of this study was to examine the presence of neuropathic pain and CS above the spinal lesion in SCI, and to investigate whether injury characteristics or medication influenced pain response. Methods Twenty-four SCI patients with various injury characteristics (eight subacute, traumatic injuries, eight chronic, traumatic injuries, eight non-traumatic injuries) and 12 able-bodied controls underwent sensory testing:pressure algometry, Von Frey filaments (sensitivity), and repetitive pinprick stimulation (pain windup). SCI participants also fulfilled a modified version of the McGill Pain Questionnaire. Data were analyzed regarding (i) SCI patients compared with controlgroup and (ii) SCI subgroup comparison (grouped by a) injury characteristics and (b) intake of analgesics, where low-medicated subgroup were prescribed only non-opioids and high-medicated potent opioids). Results Neuropathic pain was present in 21 of 24 SCI patients. Chronic and non-traumatic SCI patients reported considerably higher present pain intensity than sub-acute traumatic SCI patients on a five-point scale (3.13±0.99, 1.75±1.75 and 0.13±0.35, respectively, p<0.005). Reduced pressure pain detection thresholds (PPDT) were found in SCI patients at several supra-lesional anatomical points compared to controls. Contrarily, tactile detection thresholds were higher in SCI. SCI subgroup analyses showed that i) the low-medicated SCI subgroup displayed significantly lower PPDT compared to the high-medicated subgroup, ii) pain-windup was present in all subgroups although the sub-acute and non-traumatic subgroups displayed lesser pain windup than controls, and the chronic SCI subgroup mainly displayed higher pain windup. Conclusions The reduced PPDT found above lesion suggests the presence of CS in SCI. However, findings regarding SCI subgroup comparison did not support our hypothesis that more medication leads to increased CS. Implications The development of CS may complicate diagnosis and pain treatment following SCI. Prospective studies of SCI with a healthy control group are needed.

Efficacy of Internet-Delivered Mindfulness for Improving Depression in Caregivers of People With Spinal Cord Injuries and Chronic Neuropathic Pain: A Randomized Controlled Feasibility Trial

ObjectivesTo explore the feasibility and efficacy of web-based mindfulness training for carers of people with spinal cord injury (SCI). DesignRandomized controlled feasibility study with 3-month follow-up. SettingCommunity setting. ParticipantsSpouses or family caregivers (N=55) of people with SCI and chronic neuropathic pain were recruited via the direct care team and advertisements. Participants were older than 18 years (no upper age limit), with Internet access for the duration of the study. Participants were randomly allocated to an 8-week online mindfulness training intervention (n=28), or to receive 8 weeks of psychoeducational materials on SCI and chronic pain (n=27). InterventionsAn established web-based, mindfulness training course was delivered over 8 weeks. Participants completed 10 minutes of mindfulness practices, twice per day, 6 days per week, totaling 960 minutes. The control group received a weekly e-mail with psychoeducational materials (based on the established elements) on SCI and pain for 8 weeks. Main Outcome MeasureDepression severity. ResultsMindfulness reduced depression severity more than psychoeducation at T2 (mean difference= −.891; 95% confidence interval,−1.48 to −.30) and T3 (mean difference=−1.96; 95% confidence interval, −2.94 to −.97). Mindfulness training also reduced anxiety at T2 (mean difference=−.888; 95% confidence interval, −1.40 to −.38) and T3 (mean difference=−2.44; 95% confidence interval, −3.20 to −1.69). ConclusionsResults indicate that Internet-delivered mindfulness training offers unique benefits and is viable for caregivers of people with SCI and chronic neuropathic pain. Further work should explore the feasibility of combined education and mindfulness training incorporating both patient and caregiver, for optimum benefit.

Neuropathic Pain After Spinal Cord Injury: Challenges and Research Perspectives.

Neuropathic pain is a debilitating consequence of spinal cord injury (SCI) that remains difficult to treat because underlying mechanisms are not yet fully understood. In part, this is due to limitations of evaluating neuropathic pain in animal models in general, and SCI rodents in particular. Though pain in patients is primarily spontaneous, with relatively few patients experiencing evoked pains, animal models of SCI pain have primarily relied upon evoked withdrawals. Greater use of operant tasks for evaluation of the affective dimension of pain in rodents is needed, but these tests have their own limitations such that additional studies of the relationship between evoked withdrawals and operant outcomes are recommended. In preclinical SCI models, enhanced reflex withdrawal or pain responses can arise from pathological changes that occur at any point along the sensory neuraxis. Use of quantitative sensory testing for identification of optimal treatment approach may yield improved identification of treatment options and clinical trial design. Additionally, a better understanding of the differences between mechanisms contributing to at- versus below-level neuropathic pain and neuropathic pain versus spasticity may shed insights into novel treatment options. Finally, the role of patient characteristics such as age and sex in pathogenesis of neuropathic SCI pain remains to be addressed.

Granulocyte Colony-Stimulating Factor (G-CSF) for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a common medical condition with a poor prognosis for recovery and catastrophic effects on a patient's quality of life. Available treatments for SCI are limited, and the evidence suggesting their harmful side effects is more consistent than any suggestion of clinical benefit. Developing novel safe and effective therapeutic options for SCI is crucial. Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine with known multifaceted effects on the central nervous system. Herein, we review the accumulating preclinical evidence for the beneficial effects of G-CSF on functional and structural outcomes after SCI. Meanwhile we present and discuss multiple mechanisms for G-CSF's neuroprotective and neuroregenerative actions through the results of these studies. In addition, we present the available clinical evidence indicating the efficacy and safety of G-CSF administration for the treatment of acute and chronic traumatic SCI, compression myelopathy, and SCI-associated neuropathic pain. Our review indicates that although the quality of clinical evidence regarding the use of G-CSF in SCI is inadequate, the encouraging available preclinical and clinical data warrant its further clinical development, and bring new hope to the longstanding challenge that is treatment of SCI.

Successful spinal cord stimulation for neuropathic below-level spinal cord injury pain following complete paraplegia: a case report.

Neuropathic pain is common in patients with spinal cord injury (SCI) and often difficult to treat. We report a case where epidural spinal cord stimulation (SCS) below the level of injury has been successfully applied in a patient with a complete spinal cord lesion. A 53-year-old female presented with neuropathic below-level SCI pain of both lower legs and feet due to complete SCI below T5. Time and pain duration since injury was 2 years. Pain intensity was reported on numeric rating scale with an average of 7/10 (0 meaning no pain, 10 meaning the worst imaginable pain), but also with about 8-10 pain attacks during the day with an intensity of 9/10, which lasted between some minutes and half an hour. SCS was applied below the level of injury at-level T11-L1. After a successful 2 weeks testing period the pulse generator has been implanted permanently with a burst-stimulation pattern. The average pain was reduced to a bearable intensity of 4/10, in addition attacks could be reduced both in frequency and in intensity. This effects lasted for at least three months of follow-up. Even in case of complete SCI, SCS might be effective. Mechanisms of pain relief remain unclear. A modulation of suggested residual spinothalamic tract function may play a role. Further investigation has to be carried out to support this theory.

Usefulness of laser-evoked potentials and quantitative sensory testing in the diagnosis of neuropathic spinal cord injury pain: a multiple case study.

A retrospective study. The aim of this study was to investigate the contribution of laser-evoked potentials (LEPs) and quantitative sensory testing (QST) to the diagnosis of neuropathic pain in patients with spinal cord injury (SCI) and inconclusive magnetic resonance imaging (MRI) findings. A multidisciplinary pain center. QST (DFNS protocol) and Tm-YAG-laser stimulation of the skin were applied within the pain site corresponding with dermatomes of altered sensation. Available MRI scans were reviewed. Thirteen individuals (50±16 years) with SCI were examined. In four cases with no detectable neural lesion on MRI, all QST but three LEP were abnormal. In four patients with poorly defined spinal lesion on MRI, all QST but three LEP only were abnormal. In four cases where pain was not matching adequately with MRI lesions, all patients had abnormal LEP and QST. In one patient showing a spinal cord atrophy, LEP was normal but QST was abnormal. Findings supported the diagnoses at-level (n=5) and below-level (n=8) SCI pain. Spinothalamic tract function assessed by LEP was normal in three cases, but QST was abnormal in all cases. As QST is a psychophysical examination depending on patient cooperation, we suggest that the combination of QST and LEP might be a valuable diagnostic tool to detect lesions of the somatosensory system in a subgroup of patients with neuropathic spinal cord injury pain and inconclusive MRI findings.

Advancing research and clinical care in the management of neuropathic pain after spinal cord injury: Key findings from a Canadian summit

ABSTRACTBackground: Optimal management of neuropathic pain (NP) is essential to enhancing health-related quality of life for individuals living with spinal cord injury (SCI). A key strategic priority for the Ontario Neurotrauma Foundation (ONF) and Rick Hansen Institute (RHI) is optimizing NP management after SCI.Aims: A National Canadian Summit, sponsored by ONF and RHI, was held to develop a strategic plan to improve NP management after SCI.Methods: In a one-day meeting held in Toronto, Ontario, a multidisciplinary panel of 18 Canadian stakeholders utilized a consensus workshop methodology to (1) describe the current state of the field, (2) create a long-term vision, and (3) identify steps for moving into action.Results: A review of the current state of the field identified strengths including rigourously developed evidence syntheses and practice landscape documentation. Identified gaps included limited evidence on NP hindering recommendation development in evidence syntheses, absence of a national strategy, care silos with limited cross-continuum connections, limited consumer involvement, and limited practice standard implementation. The panel identified key themes for a long-term vision to improve the management of SCI NP in Canada, including establishing an integrated collaborative network; standardized care and outcome evaluation; education; advocacy; and directing resources to innovative solutions. The panel identified the next step as prioritization of areas that will have the greatest impact in a 5-year time frame.Conclusion: A strategic plan outlining a long-term vision to improve management of NP after SCI in Canada was developed and will inform future activities of the sponsors.

Dopaminergic treatment of restless legs syndrome in spinal cord injury patients with neuropathic pain.

Recent studies report high incidence of restless legs syndrome (RLS) in patients with spinal cord injury (SCI), who may also present pain and sensory disturbances. In the present manuscript, we examine and discuss diagnostic and treatment challenges of comorbid RLS and neuropathic pain (NP) in SCI. We evaluated seven men with a mean age of 55.6 (s.d.=14.0) years, with chronic complete or incomplete SCI at the thoracic or lumbar level, for complaints of sensory disturbances in the legs, which initially were attributed to drug-resistant NP. Because overlapped RLS was suspected, clinical evaluation of NP and RLS, serum ferritin and iron level assessment, and video polysomnographic (VPSG) studies were conducted. Pramipexole (0.18 mg q.d.-1) was added to treat RLS, and a follow-up was performed at 2 months. We found that in six subjects the RLS was comorbid with NP and in one subject the symptoms of RLS were misdiagnosed as NP. VPSG revealed periodic limb movements (PLMs) in all patients, including PLMs of the legs, arms or both. Serum ferritin was <50 ng ml-1 in two patients. RLS improved significantly after 2 months with pramipexole. On the basis of current findings, we recommend physicians to be aware of the comorbidity between RLS and NP secondary to SCI to include suitable diagnostic procedures and effective treatments.

Targeting inflammation as a treatment modality for neuropathic pain in spinal cord injury: a randomized clinical trial.

BackgroundThe purpose of the present study was to examine the effectiveness of an anti-inflammatory intervention as a treatment for neuropathic pain following spinal cord injury (SCI).MethodsThis randomized, parallel-group, controlled clinical trial (NCT02099890) examined 20 participants with varying levels and severities of SCI, randomized (3:2) to either a 12-week anti-inflammatory diet, or control group. Outcome measures consisted of self-determined indices of pain as assessed using the neuropathic pain questionnaire (NPQ) and markers of inflammation as assessed by various pro- and anti-inflammatory cytokines, as well as the eicosanoids PGE2 and LTB4.ResultsA significant group × time interaction was found for sensory pain scores (p < 0.01). A Mann-Whitney test revealed that the change scores (3-month baseline) were significantly different between groups for IFN-y (U = 13.0, p = 0.01), IL-1β (U = 14.0, p = 0.01), and IL-2 (U = 12.0, p = 0.01). A Friedman test revealed the treatment group had a significant reduction in IFN-y (x2 = 8.67, p = 0.01), IL-1β (x2 = 17.78, p < 0.01), IL-6 (x2 = 6.17, p < 0.05), while the control group showed no significant change in any inflammatory mediator. A stepwise backward elimination multiple regression analysis showed that the change in sensory neuropathic pain was a function of the change in the proinflammatory cytokines IL-2 and IFN-y, as well as the eicosanoid PGE2 (R = 0.689, R2 = 0.474).ConclusionsOverall, the results of the study demonstrate the efficacy of targeting inflammation as a means of treating neuropathic pain in SCI, with a potential mechanism relating to the reduction in proinflammatory cytokines and PGE2.Trial registrationClinicalTrials.gov, NCT02099890Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0625-4) contains supplementary material, which is available to authorized users.

Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: a randomized, double-blind, placebo-controlled trial.

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.

Intrathecal Transplantation of Embryonic Stem Cell-Derived Spinal GABAergic Neural Precursor Cells Attenuates Neuropathic Pain in a Spinal Cord Injury Rat Model.

Neuropathic pain following spinal cord injury (SCI) is a devastating disease characterized by spontaneous pain such as hyperalgesia and allodynia. In this study, we investigated the therapeutic potential of ESC-derived spinal GABAergic neurons to treat neuropathic pain in a SCI rat model. Mouse embryonic stem cell-derived neural precursor cells (mESC-NPCs) were cultured in media supplemented with sonic hedgehog (SHH) and retinoic acid (RA) and efficiently differentiated into GABAergic neurons. Interestingly, low doses of SHH and RA induced MGE-like progenitors, which expressed low levels of DARPP32 and Nkx2.1 and high levels of Irx3 and Pax6. These cells subsequently generated the majority of the DARPP32(-) GABAergic neurons after in vitro differentiation. The spinal mESC-NPCs were intrathecally transplanted into the lesion area of the spinal cord around T10-T11 at 21 days after SCI. The engrafted spinal GABAergic neurons remarkably increased both the paw withdrawal threshold (PWT) below the level of the lesion and the vocalization threshold (VT) to the level of the lesion (T12, T11, and T10 vertebrae), which indicates attenuation of chronic neuropathic pain by the spinal GABAergic neurons. The transplanted cells were positive for GABA antibody staining in the injured region, and cells migrated to the injured spinal site and survived for more than 7 weeks in L4-L5. The mESC-NPC-derived spinal GABAergic neurons dramatically attenuated the chronic neuropathic pain following SCI, suggesting that the spinal GABAergic mESC-NPCs cultured with low doses of SHH and RA could be alternative cell sources for treatment of SCI neuropathic pain by stem cell-based therapies.

Auricular acupuncture for spinal cord injury related neuropathic pain: a pilot controlled clinical trial

Objective: To obtain preliminary data on the effects of an auricular acupuncture protocol, Battlefield Acupuncture (BFA), on self-reported pain intensity in persons with chronic Spinal Cord Injury (SCI) and neuropathic pain.Design: Pilot randomized delayed entry single center crossover clinical trial at an outpatient rehabilitation and integrative medicine hospital center.Methods: Chronic (> one year post injury) ASIA impairment scale A through D individuals with SCI with injury level from C3 through T12 and below level neuropathic pain with at least five on the Numeric Rating Scale (NRS) were recruited. Twenty-four subjects were randomized to either an eight-week once weekly ten-needle BFA protocol (n = 13) or to a waiting list followed by the BFA protocol (n = 11).Outcome measures: The primary outcome measure was change in the pain severity NRS. Secondary outcome was the Global Impression of Change.Results: Demographically there were no significant differences between groups. Mean pain scores at baseline were higher in acupuncture than control subjects (7.75 ± 1.54 vs. 6.25 ± 1.04, P = 0.027). Although both groups reported significant reduction in pain during the trial period, the BFA group reported more pain reduction than the delayed entry group (average change in NRS at eight weeks –2.92 ± 2.11 vs. −1.13 ± 2.14, P = 0.065). There was a significant difference in groups when a group-by-time interaction in a mixed-effect repeated measures model (P = 0.014).Conclusion: This pilot study has provided proof of concept that BFA has clinically meaningful effect on the modulation of SCI neuropathic pain.

Spinal cord injury-induced pain: mechanisms and treatments.

Pain is a common consequence of a spinal cord injury (SCI) and has a major impact on quality of life through its impact on physical function, mood and participation in work, recreational and social activities. Several types of pain typically present following SCI with central neuropathic pain being a frequent and difficult to manage occurrence. Despite advances in our understanding of the mechanisms contributing to this type of pain and an increasing number of trials examining treatment efficacy, our ability to relieve neuropathic SCI pain is still very limited. Optimal management relies upon an integrated approach that uses a combination of pharmacological and nonpharmacological options.

Needs and requests – patients and physicians voices about improving the management of spinal cord injury neuropathic pain

Purpose: The present purpose was to explore patients’ and involved physicians’ needs and requests for improving their management of neuropathic pain following spinal cord injury (SCI). Methods: Sixteen patients with SCI and neuropathic pain, and nine physicians, were interviewed in focus-groups or individual interviews. An emergent design was used and the interviews and analyses were carried out in parallel, making it possible to use and deepen new emerging knowledge. The interviews were transcribed verbatim and processed according to content analysis. Results: A final model with four themes described the results. Three themes covered the current situation: limitations in structure, lack of knowledge and competence, and frustrations. A fourth theme, needs and requests, described suggestions by patients and physicians for future improvements. Suggestions included increased participation, increased patient involvement in the pain rehabilitation process, support in the process of learning to live with pain, implementation of multi-modal pain rehabilitation, and the use of complementary treatments for neuropathic pain. Conclusion: Neuropathic pain following SCI needs to be assessed and treated using a structured, inter-disciplinary, multi-modal rehabilitation approach involving patients in planning and decision-making.Implications for RehabilitationFor improving SCI neuropathic pain management, there is a great need for individually-tailored management, planned in a dialogue on equal terms between health care and the patient.Patients desire continuity and regularity and the possibility of receiving complementary treatments for SCI neuropathic pain.Access to structured pain rehabilitation is needed.Support and tools need to be provided in the learning-to-live with pain process.

An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.

Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. The goal of this study was to evaluate the potential anti-nociceptive benefits of intensive locomotor training (ILT) on neuropathic pain consequent to traumatic SCI. Using a rodent SCI model for central neuropathic pain, ILT was initiated either 5 d after injury prior to development of neuropathic pain symptoms (the "prevention" group) or delayed until pain symptoms fully developed (∼3 weeks post-injury, the "reversal" group). The training protocol consisted of 5 d/week of a ramping protocol that started with 11 m/min for 5 min and increased in speed (+1 m/min/week) and time (1-4 minutes/week) to a maximum of two 20-min sessions/d at 15 m/min by the fourth week of training. ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.

Antidepressants Are Effective in Decreasing Neuropathic Pain After SCI: A Meta-Analysis.

To systematically review and assess the effectiveness and safety of antidepressants for neuropathic pain among individuals with spinal cord injury (SCI). A systematic search was conducted using multiple databases for relevant articles published from 1980 to April 2014. Randomized controlled trials (RCTs) involving antidepressant treatment of neuropathic pain with ≥ 3 individuals and ≥ 50% of study population with SCI were included. Two independent reviewers selected studies based on inclusion criteria and then extracted data. Pooled analysis using Cohen's d to calculate standardized mean difference, standard error, and 95% confidence interval for primary (pain) and other secondary outcomes was conducted. Four RCTs met inclusion criteria. Of these, 2 studies assessed amitriptyline, 1 trazadone, and 1 duloxetine among individuals with neuropathic SCI pain. A small effect was seen in the effectiveness of antidepressants in decreasing pain among individuals with SCI (standardized mean difference = 0.34 ± 0.15; 95% CI, 0.05-0.62; P = .02). A number needed to treat of 3.4 for 30% or more pain relief was found by pooling 2 studies. Of these, significantly higher risk of experiencing constipation (risk ratio [RR] = 1.74; 95% CI, 1.09-2.78; P = .02) and dry mouth (RR = 1.39; 95% CI, 1.04-1.85; P = .02) was found amongst individuals receiving antidepressant treatment compared to those in the control group. The current meta-analysis demonstrates that antidepressants are effective in reducing neuropathic SCI pain. However, this should be interpreted with caution due to the limited number of studies. Further evaluation of long-term therapeutic options may be required.

Living with chronic neuropathic pain after spinal cord injury: an interpretative phenomenological analysis of community experience

Purpose: This article presents an in-depth, idiographic study examining the lived experience of chronic pain following spinal cord injury (SCI). Neuropathic pain (NP) occurs in a large majority of the SCI population and is particularly intractable to treatment. It can be both psychologically and physically debilitating. This study examines how the experience of NP is mediated by its meaning to the sufferer. Methods: Semi-structured interviews were conducted with eight people with SCI and chronic NP, attending outpatient clinics at a specialist SCI Centre in the UK. Verbatim transcripts were subjected to interpretative phenomenological analysis to further understand the experience. Results: Analysis suggested that NP has powerful consequences upon the sufferer’s physical, psychological and social well-being, in line with a biopsychosocial understanding of pain. Three super-ordinate themes were identified: a perceived gap between treatments received and participants’ views of what they wanted and needed; a fight for life control and acceptance; and feeling understood by others with SCI, but isolated from the non-understanding able-bodied. Conclusions: The results are discussed in terms of the possible application of acceptance-based therapy to NP and the potential for the alleviation of the debilitating consequences of NP.Implications for RehabilitationChronic NP after SCI is often described as worse than the injury itself, often impacting upon the sufferers physical and psychological health.The experiences of persons with SCI-specific NP highlight the impact of pain on their physical, psychological and social health. This indicates that healthcare professionals should incorporate a biopsychosocial approach for managing pain post-SCI.Routine clinical follow-up of SCI patients with chronic NP, as well as comprehensive pain management treatment programmes, could address the three themes evidenced in the current study, by moving routine intervention with NP away from pain relief, towards pain management.Continued education for patients, friends, family members and healthcare professionals may be beneficial in promoting understanding and awareness of NP and its consequences following SCI.

Pathogenesis of spinal cord injury induced edema and neuropathic pain: expression of multiple isoforms of wnk1

Neuropathic pain (NP) is a common occurrence following spinal cord injury (SCI). Identification of specific molecular pathways that are involved in pain syndromes has become a major priority in current SCI research. We have investigated the role of a cation-dependent chloride transporter, Cl-regulatory protein Na(+)-K(+)-Cl(-) 1 (NKCC1), phosphorylation profile of NKCC1 and its specific involvement in neuropathic pain following contusion SCI (cSCI) using a rat model. Administration of the NKCC1 inhibitor bumetanide (BU) increases the mean hindpaw withdrawal latency time (WLT), thermal hyperalgesia (TH) following cSCI. These results demonstrate implication of NKCC1 co-transporter and BUin SCI-induced neuropathic pain. The with-no-lysine (K)-1 (WNK1) kinase has been shown to be an important regulator of NKCC1 phosphorylation in many systems, including nocioception. Mutations in a neuronal-specific exon of WNK1 (HSN2) was identified in patients that have hereditary sensory neuropathy type II (HSANII) also implicates WNK1 in nocioception, such that these patients have loss of perception to pain, touch and heat. In our ongoing research we proposed two studies utilizing our contusion SCI (cSCI) NP model of rat. Study 1 aimed at NKCC1 expression and activity is up-regulated following cSCI in the early edema and chronic neuropathic pain phases. Study 2 aimed at identifying the expression profile of alternatively spliced WNK1 isoforms in animals exhibiting thermal hyperalgesia (TH) following cSCI. Adult male Sprague Dawley rats (275-300 g) following laminectomy received cSCI at T9 with the NYU impactor-device II by dropping 10 g weight from the height of 12.5 mm. Control rats obtained laminectomy but no impaction. Following injury, functional recovery was assessed by BBB locomotor scores on day 1, 7, 14, 21, 35, and 42 and development of thermal hyperalgesia on day 21, 28, 35, and 42 day of injury by monitoring hind paw withdraw latency time (WLT) in seconds compared with the baseline data before injury. Increased NKCC1 may explain observed increase in magnetic resonance imaging (MRI) T2, exhibiting NKCC1 localization in neurons. This data supports NKCC1's role in the pathogenesis of acute and chronic phases of injury, namely spinal cord edema and chronic phase neuropathic pain. NKCC1 dependent chloride influx requires the phosphorylation at specific residues. Probing for the HSN2 exon of WNK1 reveals two key findings: i) the HSN2 exon is found in alternatively spliced neuronal isoforms found at 250 kDa and 230 kDa; ii) the 250 kDa isoform is found only in tissue that is injured. This data implicates the NKCC1/WNK1/WNK1HSN2 involvement in post-injury response that contributes to the development of neuropathic pain. Targeting this system may have therapeutic benefit.