Treatment Of Chronic Neuropathic Pain Research Articles

Treatment of chronic neuropathic pain: purine receptor modulation.

Extracellular nucleosides and nucleotides have widespread functions in responding to physiological stress. The "purinome" encompasses 4 G-protein-coupled receptors (GPCRs) for adenosine, 8 GPCRs activated by nucleotides, 7 adenosine 5'-triphosphate-gated P2X ion channels, as well as the associated enzymes and transporters that regulate native agonist levels. Purinergic signaling modulators, such as receptor agonists and antagonists, have potential for treating chronic pain. Adenosine and its analogues potently suppress nociception in preclinical models by activating A1 and/or A3 adenosine receptors (ARs), but safely harnessing this pathway to clinically treat pain has not been achieved. Both A2AAR agonists and antagonists are efficacious in pain models. Highly selective A3AR agonists offer a novel approach to treat chronic pain. We have explored the structure activity relationship of nucleoside derivatives at this subtype using a computational structure-based approach. Novel A3AR agonists for pain control containing a bicyclic ring system (bicyclo [3.1.0] hexane) in place of ribose were designed and screened using an in vivo phenotypic model, which reflected both pharmacokinetic and pharmacodynamic parameters. High specificity (>10,000-fold selective for A3AR) was achieved with the aid of receptor homology models based on related GPCR structures. These A3AR agonists are well tolerated in vivo and highly efficacious in models of chronic neuropathic pain. Furthermore, signaling molecules acting at P2X3, P2X4, P2X7, and P2Y12Rs play critical roles in maladaptive pain neuroplasticity, and their antagonists reduce chronic or inflammatory pain, and, therefore, purine receptor modulation is a promising approach for future pain therapeutics. Structurally novel antagonists for these nucleotide receptors were discovered recently.

Surgical Treatment of Chronic Neuropathic Pain

Surgical Treatment of Chronic Neuropathic Pain

Nonlinear Relation Between Burst Dorsal Root Ganglion Stimulation Amplitude and Behavioral Outcome in an Experimental Model of Painful Diabetic Peripheral Neuropathy

Background and objectiveDorsal root ganglion stimulation (DRGS) has recently emerged as a neuromodulation modality in the treatment of chronic neuropathic pain. The objective of this study was to compare the efficacy of different Burst‐DRGS amplitudes in an experimental model of painful diabetic peripheral neuropathy (PDPN).MethodsDiabetes mellitus was induced in female Sprague–Dawley rats by intraperitoneal injection of streptozotocin (STZ, n = 28). Animals were tested for mechanical hypersensitivity (von Frey paw withdrawal test) before, and four weeks after STZ injection. PDPN rats (n = 13) were implanted with a unilateral bipolar electrode at the L5 DRG. Animals received Burst‐DRGS at 0%, 10%, 33%, 50%, 66%, and 80% of motor threshold (MT) in a randomized crossover design on post‐implantation days 2–7 (n = 9). Mechanical hypersensitivity was assessed before stimulation onset, 15 and 30 min during stimulation, and 15 and 30 min after stimulation.ResultsBurst‐DRGS at amplitudes of 33%, 50%, 66%, and 80% MT resulted in significant attenuation of STZ‐induced mechanical hypersensitivity at 15 and 30 min during stimulation, as well as 15 min after cessation of stimulation. No effect on mechanical hypersensitivity was observed for Burst‐DRGS at 0% MT and 10% MT. Optimal pain relief and highest responder rates were achieved with Burst‐DRGS at 50–66% MT, with an estimated optimum at 52% MT.ConclusionOur findings indicate a nonlinear relationship between Burst‐DRGS amplitude and behavioral outcome, with an estimated optimal amplitude of 52% MT. Further optimization and analysis of DRGS driven by insights into the underlying mechanisms related to the various stimulation paradigms is warranted.

Dorsal Root Ganglion Stimulation in Experimental Painful Diabetic Peripheral Neuropathy: Burst vs. Conventional Stimulation Paradigm

ObjectivesPainful diabetic peripheral neuropathy (PDPN) is a long‐term complication of diabetes mellitus (DM). Dorsal Root Ganglion Stimulation (DRGS) has recently emerged as a neuromodulation modality in the treatment of chronic neuropathic pain. The objective of this study was to compare the effect of burst DRGS (Burst‐DRGS) and conventional DRGS (Con‐DRGS) in an experimental model of PDPN.Materials and MethodsDM was induced in female Sprague–Dawley rats by intraperitoneal injection of streptozotocin (STZ, n = 48). Animals were tested for mechanical hypersensitivity (50% hind paw withdrawal threshold on Von Frey test) before, and 4 weeks after STZ injection. PDPN rats were then implanted with a unilateral bipolar lead at the L5 DRG (n = 22) and were stimulated for 30 min at days 2 and 3 postimplantation. Animals received Con‐DRGS and Burst‐DRGS in a randomized crossover design (n = 10), or received Sham‐DRGS (n = 7) for 30 min, and were tested for mechanical hypersensitivity at baseline, 15 and 30 min during DRGS, and 15 and 30 min following DRGS. Five animals were withdrawn from the study due to electrode‐related technical problems.ResultsCon‐DRGS and Burst‐DRGS normalized STZ‐induced mechanical hypersensitivity at 15 and 30 min during stimulation. A significant difference in terms of mechanical hypersensitivity was observed between both of the stimulated groups and the Sham‐DRGS group at 15 and 30 min during stimulation. Interestingly, Burst‐DRGS showed signs of a residual effect at 15 min after cessation of stimulation, while this was not the case for Con‐DRGS.ConclusionsUnder the conditions tested, Con‐DRGS and Burst‐DRGS are equally effective in attenuating STZ‐induced mechanical hypersensitivity in an animal model of PDPN. Burst‐DRGS showed signs of a residual effect at 15 min after cessation of stimulation, which requires further investigation.

Perioperative duloxetine for acute postoperative analgesia: a meta-analysis of randomized trials

BackgroundMultimodal analgesia is a fundamental part of modern surgery and enhanced recovery pathways. Duloxetine, a serotonin and norepinephrine reuptake inhibitor, has been validated for the treatment of chronic neuropathic pain....

Identifying Plasma Derived Extracellular Vesicle (EV) Contained Biomarkers in the Development of Chronic Neuropathic Pain

Research into potentially novel biomarkers for chronic pain development is lacking. microRNAs (miRNAs) are attractive candidates as biomarkers due to their conservation across species, stability in liquid biopsies, and variation that corresponds to a pathologic state. miRNAs can be sorted into extracellular vesicles (EVs) within the cell and released from the site of injury. EVs transfer cargo molecules between cells thus affecting key intercellular signaling pathways. The focus of this study was to determine the plasma derived EV miRNA content in a chronic neuropathic pain rat model. This was accomplished by performing either spinal nerve ligation (SNL; n = 6) or sham (n = 6) surgery on anesthetized male Sprague-Dawley rats. Mechanosensitivity was assessed and plasma derived EV RNA was isolated at baseline (BL), day 3, and 15 postnerve injury. EV extracted small RNA was sequenced followed by differentially expressed (DE) miRNAs and gene target enrichment/signaling pathway analysis performed using R packages and TargetScan/Ingenuity pathway analysis (IPA), respectively. Seven of the DE miRNAs were validated by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). The data indicated that SNL rats displayed a time-dependent threshold reduction in response to evoked stimuli from day 3 to day 15 postnerve injury. The data also revealed that 22 and 74 miRNAs at day 3 and 15, respectively, and 33 miRNAs at both day 3 and 15 were uniquely DE between the SNL and sham groups. The key findings from this proposal include (1) the majority of the DE EV miRNAs, which normally function to suppress inflammation, were downregulated, and (2) several of the plasma derived DE EV miRNAs reflect previously observed changes in the injured L5 nerve. The plasma derived DE EV miRNAs regulate processes important in the development and maintenance of neuropathic pain states and potentially serve as key regulators, biomarkers, and targets in the progression and treatment of chronic neuropathic pain. PerspectiveThis article describes the DE miRNA content of plasma derived EVs, comparing neuropathic pain to normal conditions. This data indicates that EV miRNAs may be important in nociception and may also serve as biomarkers for chronic pain. These results encourage further research on EV miRNAs in chronic neuropathic pain sufferers.

The use of high-dose cervical spinal cord stimulation in the treatment of chronic upper extremity and neck pain.

Background:Dorsal column spinal cord stimulation is used for the treatment of chronic neuropathic pain of the axial spine and extremities. Recently, high-dose (HD) thoracic dorsal column stimulation for paresthesias has been successful. This study evaluates the utility of HD stimulation in the cervical spine for managing upper neck and upper extremity pain and paresthesias.Methods:Three patients suffering from cervical and upper extremity chronic pain were assessed. Each underwent a two-stage process that included a trial period, followed by permanent stimulator implantation. Therapy included the latest HD stimulation settings including a pulse width of 90 μs, a frequency setting of 1000 Hz, and an amplitude range of 1.5 amps–2.0 amps. Pain relief was measured utilizing relative percent pain improvement as self-reported by each patient before and after surgery.Results:After permanent implantation, (range 15–21 months), all three patients continued to experience persistent pain and paresthesia relief (70%–90%).Conclusions:In three patients, HD cervical spinal cord stimulation successfully controlled upper extremity chronic pain/paresthesias.

Botulinum toxin type A in chronic neuropathic pain in refractory leprosy

Neuropathic pain is a chronic syndrome that is difficult to treat and often affects patients with leprosy. Recommended treatment includes the the use of analgesic drugs, codeine, tricyclic antidepressants, neuroleptics, anticonvulsants and thalidomide, but without consensus on uniform dose and fully satisfactory results. To analyze botulinum toxin type A (BoNT-A) effectiveness in treatment of chronic neuropathic pain in refractory leprous patients, as well as evaluate and compare the quality of life of patients before and after using the medication. We used a specific protocol including clinical, demographic, DN4 protocol, analogue scale (VAS), sensory evaluation and evaluation of the WHOQOL-BREF. Therapeutic intervention was performed with BOTOX® BTX-A 100U administered subcutaneously. Fifteen patients were evaluated on days 0, 10 and 60. Patients on VAS showed pain between 5 and 10, in one case there was complete pain relief in 60 days, while others showed improvement in the first week with the return of symptoms with less intensity after this period. WHOQOL-BREF's domains Quality of Life and Physical to have a significant increase in QOL. BoNT-A proved to be a good therapeutic option in relieving pain with improved quality of life for these patients.

Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review.

Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain.

Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats.

Neuropathic pain (NP) has complicated pathogenesis as it mainly involves a lesion or dysfunction of the somatosensory nervous system and its clinical treatment remains challenging. Chronic constriction injury (CCI) model is a widely used neuropathic pain model and involved in mechanisms including both nerve inflammatory and injury. Cytokines and their receptors play essential roles in the occurrence and persistence of neuropathic pain, but the underlying mechanisms have not well been understood. Therefore, Interleukin-1 receptor-associated kinase 1 (IRAK1) is chosen to explore the possible mechanisms of NP. In the present study, IRAK1 was found to persistently increase in the dorsal root ganglion (DRG) and spinal cord (SC) during CCI detected by western blot. The staining further confirmed that IRAK1 was mainly co-located in the DRG astrocytes or SC neurons, but less in the DRG microglia or SC astrocytes. Moreover, the region of increased IRAK1 expression was observed in superficial laminae of the spinal dorsal horn, which was the nociceptive neuronal expression domain, suggesting that IRAK1 may mediated CCI-induced pain by nociceptive primary afferent. In addition, intrathecal injection of Toll-like receptor 4 (TLR4) inhibitor or IRAK1 siRNA decreased the expression of IRAK1 accompanied with the alleviation of CCI-induced neuropathic pain. The upregulation of p-NF-κB expression was reversed by IRAK1 siRNA in SC, and intrathecal injection of p-NF-κB inhibitor relieved neuropathic pain. Taking together, targeting IRAK1 may be a potential treatment for chronic neuropathic pain.

A Cost-Effectiveness Model for Adjunctive Smoked Cannabis in the Treatment of Chronic Neuropathic Pain.

Background: A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy.Materials and Methods: A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis.Results: Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective.Conclusion: As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.

Gabapentin versus Transdermal Fentanyl Matrix for the Alleviation of Chronic Neuropathic Pain of Radicular Origin: A Randomized Blind Multicentered Parallel-Group Noninferiority Trial.

A number of studies have been published proposing various approaches to the treatment of neuropathic pain; however, to our knowledge, no attempts have been made to compare gabapentin and fentanyl in patients with lumbar radiculopathy. We evaluated the relative efficacy and safety of fentanyl matrix and gabapentin for the treatment of chronic neuropathic pain of radicular origin. The study was designed as a randomized blind multicentered parallel-group noninferiority trial. A total of 108 patients with moderate-to-severe pain (≥4 intensity on an 11-point numeric rating scale) were randomly prescribed either fentanyl matrix or gabapentin over a period of 56 days. In the primary analysis, the noninferiority of fentanyl matrix treatment was evaluated in relation to the efficacy of gabapentin based on the pain intensity difference (PID) at 56 days after the first dose of the drugs. Secondary endpoints included pain relief, improvement in functional status (the Korean-Oswestry Disability Index (K-ODI)), improvement in depressive symptoms (Korean-Beck Depression Index (K-BDI)) between the 28th and 56th day, and adverse events (AEs). Analysis of the primary efficacy endpoint established the noninferiority of fentanyl matrix compared with gabapentin, with no statistically significant difference observed in the PID after 56 days for the two treatment groups. Similarly, analysis of pain relief revealed no significant differences between the groups on days 28 and 56. There was no difference in the K-ODI and K-BDI between the groups during the study period. The overall incidence of at least one AE was similar for fentanyl matrix (67.3%) and gabapentin (69.6%). The most commonly reported AEs for patients treated with fentanyl matrix and gabapentin included dizziness (30.8% vs. 44.6%, respectively), somnolence (26.9% vs. 35.7%), and constipation (15.4% vs. 17.9%). This study demonstrated that the analgesic effect of fentanyl matrix is noninferior in comparison with gabapentin and supports the use of fentanyl matrix as an effective and safe treatment for moderate-to-severe chronic neuropathic pain. This trial is registered with NCT01127100.

Quality of Life After Motor Cortex Stimulation: Clinical Results and Systematic Review of the Literature.

Motor cortex stimulation (MCS) is routinely used for the treatment of chronic neuropathic pain but its effect on quality of life remains uncertain. To systematically review the published literature on MCS and quality of life and report the effects of this therapy in a series of patients prospectively followed in our center. The systematic literature review was conducted using the search words "motor cortex stimulation and pain and neurosurgery" and "motor cortex stimulation and pain and quality of life." Quality of life in our clinical trial was investigated in a series of 10 patients with chronic neuropathic pain prospectively followed for 12 mo after MCS. Two hundred eighteen nonreplicated articles were pooled for analysis. Of these, 6 described measures of quality of life in the pre- and postoperative period. In these studies, 64 patients with different clinical conditions associated with neuropathic pain were followed for 6 to 84 mo after MCS surgery. Improvement in quality of life ranged from 35% to 85%. In our clinical series, visual analog scale (VAS), SF-12 physical (PhysCS), and mental scores (MenCS) recorded 12 mo after MCS were improved by 60±10% (P=.002), 50±13% (P=.002), and 22±6% (P=.01), respectively. No significant correlation was found between postoperative improvement in pain and either PhysCS (r=0.18; P=.6) or MenCS (r=-0.24; P=.5). MCS improves quality of life in patients with chronic refractory neuropathic pain. Additional factors other than a simple analgesic effect may contribute to these results.

Chronic neuropathic pain following inguinal hernia repair

Since recurrence rates have been considerably reduced with mesh repairs, chronic pain has recently become the main concern after inguinal hernia repair (IHR), with significant impact on patient satisfaction, societal cost, and quality of life. Some 31% of all patients with persistent postsurgical pain develop neuropathic pain (NP) after IHR seeing that the inguinal nerves that cross the surgical field can directly or indirectly be damaged. Because of the multiplicity of the risk factors and the complexity of the pathophysiological mechanisms, substantial attention has been devoted to the multidisciplinary approaches and to the preventive measures. More clinical trials are needed to improve the level of evidence of the use of pharmacological, surgical, and interventional procedures in both prevention and treatment of chronic NP following IHR. In this article, the current objectives are to review the incidence, risk factors, pathogenesis, diagnosis, prevention, and treatment of chronic NP after IHR.

A Review of Cannabis in Chronic Kidney Disease Symptom Management.

Purpose of Review:Physical and psychological symptom burden in patients with advanced chronic kidney disease (CKD) is significantly debilitating; yet, it is often inadequately treated. Legalization of cannabis in Canada may attract increasing interest from patients for its medical use in refractory symptom management, but its indications and long-term adverse health impacts are poorly established, creating a challenge for clinicians to support its use. In this review, we summarize key clinical studies and the level of evidence for nonsynthetic cannabinoids in the treatment of common symptoms encountered in advanced stages of CKD, including chronic pain, nausea and vomiting, anorexia, pruritus, and insomnia.Sources of Information:Medline and EmbaseMethods:A search was conducted in MEDLINE and EMBASE (inception to March 1, 2018) on cannabis and CKD symptoms of interest, complemented with a manual review of bibliographies. Studies that examined synthetic cannabinoids that are manufactured to mimic the effects of ∆9-tetrahydrocannabinol such as dronabinol, levonantradol, nabilone, and ajulemic acid were excluded. We focused on studies with higher level of evidence where available, and quality of studies was graded based on the Oxford Centre for Evidence-based Medicine Levels of Evidence (1a to 5).Findings:Based on studies conducted in patients without renal impairment, those treated with nonsynthetic cannabinoids were 43% to 300% more likely to report a ≥30% reduction in chronic neuropathic pain compared with placebo. However, there is currently insufficient evidence to recommend nonsynthetic cannabinoids for other medical indications, although preliminary investigation into topical endocannabinoids for uremia-induced pruritus in end-stage renal disease is promising. Finally, any benefits of cannabis may be offset by potential harms in the form of cognitive impairment, increased risk of mortality post-myocardial infarction, orthostatic hypotension, respiratory irritation, and malignancies (with smoked cannabis).Limitations:Nonsynthetic cannabinoid preparations were highly variable between studies, sample sizes were small, and study durations were short. Due to an absence of studies conducted in CKD, recommendations were primarily extrapolated from the general population.Implications:Until further studies are conducted, the role of nonsynthetic cannabinoids for symptom management in patients with CKD should be limited to the treatment of chronic neuropathic pain. Clinicians need to be cognizant that nonsynthetic cannabinoid preparations, particularly smoked cannabis, can pose significant health risks and these must be cautiously weighed against the limited substantiated therapeutic benefits of cannabis in patients with CKD.

Translocation Associated Membrane Protein 1 Contributes to Chronic Constriction Injury-Induced Neuropathic Pain in the Dorsal Root Ganglion and Spinal Cord in Rats

Neuropathic pain is a severe debilitating state caused by injury or dysfunction of somatosensory nervous system, and the clinical treatment is still challenging. Translocation associated membrane protein 1 (TRAM1), an adapter protein, participates in a variety of transduction pathways and mediates the biological functions such as cell proliferation, activation, and differentiation. However, whether TRAM1 is involved in the pathogenesis of neuropathic pain is still unclear. In our study, we reported the role of TRAM1 in the maintenance of neuropathic pain induced by chronic constriction injury (CCI) on rats. By western blot and staining, we found that TRAM1 increased in the dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons after CCI. Being similar to IB4-, CGRP-positive expressed area, TRAM1 also expressed in the superficial laminae of the spinal cord dorsal horn (SCDH), suggesting it was related to the innervations of the primary afferents. Moreover, intrathecal injection of TRAM1 siRNA or Toll-like receptor 4 (TLR4) inhibitor induced low expression of TRAM1 in SC, which alleviated the pain response induced by CCI. The upregulation of p-NF-κB expression was reversed by TRAM1 siRNA in SC and DRG, and intrathecal injection of p-NF-κB inhibitor relieved neuropathic pain. All the data indicated that TRAM1 could take part in CCI-induced pain and might be a potential treatment for chronic neuropathic pain.

Predicting factors of outcome in multidisciplinary treatment of chronic neuropathic pain.

PurposeEvidence of the effectiveness of multidisciplinary treatment with a focus on neuropathic pain is still rare. The present study investigated whether multidisciplinary treatment leads to improvement of neuropathic pain in outcome (pain intensity and disability) and psychological (depression, pain acceptance, and catastrophizing) variables at posttreatment and 3-month follow-up. We examined whether and to what extent psychological changes can predict long-term outcome at 3-month follow-up, when other variables are controlled for (baseline characteristics and changes in pain parameters).Patients and methodsPatients suffering from a chronic neuropathic pain condition (n=141) attended an inpatient multidisciplinary program lasting about 15 continuous days with self-report data collected at pretreatment, posttreatment, and 3-month follow-up.ResultsRepeated-measures ANOVAs showed a significant improvement of pain intensity, disability, pain acceptance, catastrophizing, and depression at posttreatment. These improvements remained stable over the 3-month follow-up for all variables except for depression. The inclusion of psychological changes in multiple regression analyses greatly increased the variance in outcome, explained by baseline characteristics and changes in pain parameters.ConclusionThe results could help clinicians to determine which variables should be emphasized during inpatient treatment and during the follow-up period, in order to maintain the gains after an inpatient multidisciplinary treatment for neuropathic pain.PerspectiveThe present study demonstrates the beneficial effects of an inpatient multidisciplinary program for neuropathic pain and further question the resistant nature of neuropathic pain to treatment. The results add evidence to the relevance of cognitive-behavioral models of pain positing an important role for pain-related thoughts and emotions in long-term outcome following multidisciplinary pain treatment.

Motor Cortex Stimulation Therapy for Relief of Central Post-Stroke Pain: A Retrospective Study with Neuropathic Pain Symptom Inventory

Background: Motor cortex stimulation (MCS) has been used in the treatment of chronic neuropathic pain for more than 25 years. However, the mechanisms and outcome predictors still represent major challenges. Objectives: To investigate outcome predictors and potential mechanisms of MCS on central post-stroke pain (CPSP). Material and Methods: 16 CPSP patients were analyzed at our center. The pain intensity was assessed using a visual analog scale (VAS) before surgery and at the last follow-up. The Neuropathic Pain Symptom Inventory (NPSI) was used to assess pain intensity, analyze outcome predictors, and indicate potential mechanisms of MCS. Results: The mean VAS score before surgery (8.0 ± 0.7) was significantly higher than that of the last follow-up (5.3 ± 2.4, p < 0.001). Similarly, the mean total NPSI score before MCS (30.6 ± 12.2) was significantly reduced at the last follow-up (25.2 ± 15.1, p = 0.01). An analysis of the NPSI subscores revealed a significant association between burning pain relief and effective results (p = 0.041, Fisher’s exact test). Conclusions: Burning pain relief might predict long-term results for the therapeutic use of MCS in CPSP. The substantia gelatinosa may play an important role in the modulation of pain relief mediated by MCS.

Wednesday, September 26, 2018 1:00 PM – 2:00 PM Interventional Pain Management: 29. The use of high dose cervical spinal cord stimulation in the treatment of chronic upper extremity and neck pain

BACKGROUND CONTEXT Within the last few decades, the use of dorsal column stimulation has increased as an alternative method for the long-term treatment of chronic neuropathic pain of the axial spine and extremities. The explicit purpose of this therapy has been to replace pain in the affected area with a more favorable paresthesia. However, the electrical stimulation may elicit paresthesias which are unfavorable to a subset of patients making the therapy untenable despite adequate pain control. To address this issue, an innovative form of high-dose (HD) programming that utilizes a range of frequencies which provide paresthesia-free pain control has been clinically successful in thoracic dorsal column stimulation. To date, no such use of HD programming has been reported in cervical dorsal column stimulation. PURPOSE The purpose of this study is to evaluate the utility of high-dose stimulation in the cervical spine for the paresthesia-free treatment of upper extremity and neck pain. STUDY DESIGN/SETTING The study design follows a retrospective analysis to evaluate the history, treatment conditions and results of three patients with chronic upper extremity and neck pain treated with high-dose cervical spinal cord stimulation. A review of the literature regarding cervical spinal cord stimulation and the current state of high-dose stimulation was also undertaken. PATIENT SAMPLE Three patients, two male and one female, were included in the case series. The first patient, a 43 year old male, suffered from post-traumatic neck and right upper extremity neuropathic pain as a result of ballistic cervical spinal cord injury. The second patient, a 68 year male, presented with cervical degenerative foraminal and central moderate stenosis from C2 through C7 with neck pain and bilateral radiculopathy. The third patient, a 32 year old female, was referred for left upper extremity chronic regional pain syndrome after a work related injury, without significant cervical pathology. OUTCOME MEASURES Outcome measures in this case series were evaluated through the typical method of identifying candidacy for permanent dorsal column stimulator implantation, specifically relative percent pain relief with and without stimulation. METHODS Patients were evaluated preoperatively both clinically and radiographically to determine candidacy for a stimulator trial. Adequate patency of the cervical spinal canal on MRI and pain locations amenable to cervical spinal cord stimulation were found to be present in all patients. Each patient then underwent a stage 1 cervical spinal cord stimulator placement with externalized extension leads. Specifically, two 1 × 8 percutaneous Medtronic epidural arrays were advanced to the level of C2-3 bilaterally or eccentric to the affected side. A five-day trial of both low-dose paresthesia and high-dose paresthesia-free therapy was applied. All patients experienced greater than 50% pain relief (range 70%–90%) without paresthesias and requested permanent implantation. Stage 2 extension lead removal with generator connection and implantation was performed in all three cases using the Medtronic Intellis rechargeable generator without complication and with persistent and current paresthesia-free pain control since implantation (range 6-12 months). RESULTS During the trial period, all patients experienced greater than 50% pain relief (range 70%–90%) without paresthesias utilizing high-dose programming. Pain returned to baseline levels with the device off. Low-dose therapy was applied during the trial period as well, resulting in all cases with similar pain relief, but with the presence of paresthesias, which in all cases was less favorable to the paresthesia-free high-dose programming. After permanent implantation, all three patients continue to experience persistent and current paresthesia-free pain control (range 6-12 months). CONCLUSIONS This retrospective case series first reports and demonstrates the effectiveness of high-dose cervical spinal cord stimulation in the paresthesia-free treatment of a variety of upper extremity chronic pain generators. This suggests a potential benefit to a subset of patients who may benefit from cervical spinal cord stimulation but defer therapy due to unfavorable paresthesias. In the future, a larger study should be conducted in order to fully understand the use of high-dose cervical spinal cord stimulation. Medtronic Spinal Cord Stimulator (Approved for this indication) FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Spinal Cord Stimulation for Neuropathic Pain: Current Trends and Future Applications

The origin and the neural pathways involved in chronic neuropathic pain are still not extensively understood. For this reason, despite the wide variety of pain medications available on the market, neuropathic pain is challenging to treat. The present therapeutic alternative considered as the gold standard for many kinds of chronic neuropathic pain is epidural spinal cord stimulation (SCS). Despite its proved efficacy, the favourable cost-effectiveness when compared to the long-term use of poorly effective drugs and the expanding array of indications and technical improvements, SCS is still worldwide largely neglected by general practitioners, neurologists, neurosurgeons and pain therapists, often bringing to a large delay in considering as a therapeutic option for patients affected by neuropathic chronic pain. The present state of the art of SCS in the treatment of chronic neuropathic pain is here overviewed and speculations on whether to use a trial period or direct implant, to choose between percutaneous leads or paddle electrodes and on the pros and cons of the different patterns of stimulation presently available on the market (tonic stim, high-frequency stim and burst stim) are described.