scholarly journals Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Praveen Anand ◽  
Rosario Privitera ◽  
Philippe Donatien ◽  
V. Peter Misra ◽  
David R. Woods
Keyword(s):  
Neuropathic Pain ◽  
Pain Relief ◽  
Military Service ◽  
Time Course ◽  
Rating Scale ◽  
Cold Injury ◽  
Spontaneous Pain ◽  
Nerve Fibres ◽  
Painful Neuropathy ◽  
Skin Biopsies

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

scholarly journals Long-Term Results of a Simultaneous Trial of Deep Brain and Motor Cortex Stimulation in Refractory Neuropathic Pain

2017 ◽  
Vol 3 (1) ◽  
pp. 4-15
Author(s):  
Byung-chul Son ◽  
Jin-gyu Choi ◽  
Sang-woo Ha ◽  
Deog-ryeong Kim
Keyword(s):  
Neuropathic Pain ◽  
Pain Relief ◽  
Motor Cortex ◽  
Success Rate ◽  
Rating Scale ◽  
Long Term Results ◽  
Motor Cortex Stimulation ◽  
Significant Difference ◽  
Deep Brain

Objective Although deep brain stimulation (DBS) and motor cortex stimulation (MCS) are effective in patients with refractory neuropathic pain, their application is still empirical; there is no consensus on which technique is better. Methods To enhance the success rate of trial stimulation of invasive neuromodulation techniques and identify approapriate stimulation targets in individual patients, we performed a simultaneous trial of thalamic ventralis caudalis (Vc) DBS and MCS in 11 patients with chronic neuropathic pain and assessed the results of the trial stimulation and long-term analgesia. Results Of the 11 patients implanted with both DBS and MCS electrodes, nine (81.8%) had successful trials. Seven of these nine patients (77.8%) responded to MCS, and two (18.2%) responded to Vc DBS. With long-term follow-up (56 ± 27.5 months), the mean numerical rating scale decreased significantly (P < 0.05). The degree of percentage pain relief in the chronic MCS (n = 7) and chronic DBS (n = 2) groups were 34.1% ± 18.2% and 37.5%, respectively, and there was no significant difference (P = 0.807). Five out of the seven MCS patients (71%) and both DBS patients had long-term success with the treatments, defined as >30% pain relief compared with baseline. Conclusions With simultaneous trial of DBS and MCS, we could enhance the success rate of invasive trials. Considering the initial success rate and the less invasive nature of epidural MCS over DBS, we suggest that MCS may be a better, initial means of treatment in chronic intractable neuropathic pain. Further investigations including other subcortical target-associated medial pain pathways are warranted.

scholarly journals Interleukin-6: evolving role in the management of neuropathic pain in neuroimmunological disorders

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Kenichi Serizawa ◽  
Haruna Tomizawa-Shinohara ◽  
Shota Miyake ◽  
Kenji Yogo ◽  
Yoshihiro Matsumoto
Keyword(s):  
Neuropathic Pain ◽  
Pain Intensity ◽  
Pain Score ◽  
Interleukin 6 ◽  
Rating Scale ◽  
Spontaneous Pain ◽  
Main Body ◽  
Inhibitory System ◽  
Chronic Neuropathic Pain ◽  
Limited Effectiveness

Abstract Background Neuropathic pain in neuroimmunological disorders refers to pain caused by a lesion or disease of the somatosensory system such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). MS and NMOSD are autoimmune disorders of the central nervous system, and ≥ 50% of patients with these disorders experience chronic neuropathic pain. The currently available medications for the management of neuropathic pain have limited effectiveness in patients with MS and NMOSD, and there is an unmet medical need to identify novel therapies for the management of chronic neuropathic pain in these patients. In this review article, we summarize the role of interleukin-6 (IL-6) in the pathogenesis of MS and NMOSD and the ameliorative effects of anti–IL-6 therapies in mouse models of experimental autoimmune encephalomyelitis (EAE). Main body Intraperitoneal injection of MR16-1, an anti–IL-6 receptor (IL-6R) antibody, reduced mechanical allodynia and spontaneous pain in EAE mice, which was attributed to a reduction in microglial activation and inhibition of the descending pain inhibitory system. The effect of anti–IL-6 therapies in ameliorating neuropathic pain in the clinical setting is controversial; a reduction in pain intensity has been reported with an anti–IL-6 antibody in four studies, namely a case report, a pilot study, a retrospective observational study, and a case series. Pain intensity was evaluated using a numerical rating scale (NRS), with a lower score indicating lesser pain. A reduction in the NRS score was reported in all four studies. However, in two randomized controlled trials of another anti–IL-6R antibody, the change in the visual analog scale pain score was not statistically significantly different when compared with placebo. This was attributed to the low mean pain score at baseline in both the trials and the concomitant use of medications for pain in one of the trials, which may have masked the effects of the anti–IL-6R antibody on neuropathic pain. Conclusion Thus, anti–IL-6 therapies might have a potential to reduce neuropathic pain, but further investigations are warranted to clarify the effect of inhibition of IL-6 signaling on neuropathic pain associated with MS and NMOSD.

Dynamic mechanical allodynia in the secondary hyperalgesic area in the capsaicin model—Perceptually similar phenomena as in painful neuropathy?

2011 ◽  
Vol 2 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Monika Samuelsson ◽  
Ann-Sofie Leffler ◽  
Per Hansson
Keyword(s):  
Neuropathic Pain ◽  
Pain Intensity ◽  
Healthy Subjects ◽  
Mechanical Allodynia ◽  
Secondary Site ◽  
Spontaneous Pain ◽  
Painful Neuropathy ◽  
Dynamic Mechanical ◽  
Spatial Stimulus ◽  
Stimulus Parameters

AbstractIntroductionIn order to develop valid experimental human pain models, i.e., models potentially reflecting mechanisms underlying certain expressions of clinical pain conditions, similarities and discrepancies of symptoms/signs must first and foremost be evaluated comparing the two. In a situation where symptoms/signs appear to be similar, a potential pitfall with surrogate models would be that pathophysiological mechanisms in clinical conditions and experimental models might differ, i.e., one symptom/sign may be due to several different mechanisms. Symptoms and signs caused by intradermally injected capsaicin have been suggested to reflect aspects of the clinical phenomenology of neuropathic pain, e.g., dynamic mechanical allodynia. Psychophysical characteristics of brush-evoked pain in the pain area in patients with painful peripheral neuropathy were compared with brush-evoked pain in the secondary hyperalgesic area in capsaicin-treated skin in patients and in healthy subjects using different temporo-spatial stimulus parameters.MethodNine patients were examined in the area of painful neuropathy and subsequently in the corresponding contralateral secondary site, i.e., the secondary hyperalgesic area after an intradermal capsaicin injection. Nine healthy age- and sex-matched subjects were examined in a corresponding area after capsaicin injection. Brush-evoked allodynia was induced by lightly stroking 2 different distances of the skin 2 or 4 times with brushes of 2 different widths. Intensity and duration of brush-evoked allodynia was recorded using a computerized visual analogue scale. The total brush-evoked pain intensity, including aftersensation was calculated as the area under the curve. In addition, similarities and discrepancies in the selection of sensory-discriminative and affective descriptors of the painful experience have been surveyed in the area of neuropathy and in the area of secondary hyperalgesia.ResultsAll patients reported brush-evoked pain in their area of painful neuropathy during all stimuli. Eight out of 9 patients reported brush-evoked pain in an area outside the flare in the capsaicin treated skin and only 3 out of 9 healthy subjects reported brush-evoked pain in an area outside the flare. Within patients there was no significant difference between sides regarding the influence of the various temporo-spatial stimulus parameters on the total brush-evoked pain intensity. Of all parameters tested, only increased number of strokes resulted in significantly higher brush-evoked pain intensity. The most commonly used sensory-discriminative descriptors during brush-evoked pain in the area of painful neuropathy and in the capsaicin-induced secondary hyperalgesic area in patients and controls were smarting and burning and for the affective descriptors troublesome and annoying.ConclusionsSimilarities were found regarding the influence of temporo-spatial stimulus parameters on brush-evoked allodynia in the capsaicin-induced secondary hyperalgesic area contralateral to the area of painful neuropathy and their influence when testing the area of neuropathic pain. Only 3/9 healthy subjects reported brush-evoked pain after capsaicin injection, a finding that may be related to this group reporting less spontaneous pain than the patients after injection. A hyperexcitable nervous system due to the contralateral clinical condition may also have a bearing on the frequent finding of capsaicin-induced allodynia in the patients (8/9).ImplicationsThe low prevalence of tactile allodynia in healthy volunteers makes the capsaicin model an unattractive strategy.

scholarly journals Ninjin'yoeito Alleviates Neuropathic Pain Induced by Chronic Constriction Injury in Rats

2021 ◽  
Vol 8 ◽  
Author(s):  
Risa Takemoto ◽  
Seiwa Michihara ◽  
Li-Kun Han ◽  
Nina Fujita ◽  
Ryuji Takahashi
Keyword(s):  
Neuropathic Pain ◽  
Pain Relief ◽  
Contact Area ◽  
Pain Threshold ◽  
Chronic Constriction Injury ◽  
Weight Bearing ◽  
Repeated Administration ◽  
Control Group ◽  
Spontaneous Pain ◽  
Serum Samples

Kampo medicines are frequently used empirically to treat pain in clinical practice. Ninjin'yoeito (NYT), which is associated with few adverse effects, is often used to treat the elderly, but has not yet been examined in detail. We herein investigated the effects of NYT, at 500 and 1,000 mg/kg p.o. (NYT500/NYT1000 group) in single and repeated administrations for 14 days, on pain in rats with peripheral neuropathy induced by loose ligation of the sciatic nerve (chronic constriction injury: CCI). Untreated CCI rats given distilled water were used as a control group. To assess induced pain, the pain threshold was measured using the von Frey test. To evaluate spontaneous pain, the ground-contact area of the paw with neuropathic pain was measured using the Dynamic Weight Bearing test. Serum samples were collected after the test to elucidate the mechanism of action of NYT, and brain-derived neurotrophic factor (BDNF) and corticosterone protein levels, which have been reported to change due to chronic pain, were analyzed. After single administration of NYT, the pain threshold rose in the NYT500 and NYT1000 groups. The pain threshold tended to rise on day 14 of repeated administration in the NYT500 group (p = 0.08) and it significantly rose at NYT1000 group (p &lt; 0.05) compared to Control group. In addition, the foot contact area increased (p = 0.09). Therefore, CCI-induced pain was significantly remitted and spontaneous pain was remitted after repeated administration of NYT. Serum BDNF levels were higher in untreated CCI rats than in normal rats (p = 0.05), but decreased after the repeated administration of NYT (NYT1000, p = 0.15), while serum corticosterone levels were lower (p = 0.12) than those in normal rats and increased after the repeated administration of NYT (NYT1000, p = 0.07). The blood BDNF level has been suggested to influence pain intensity. The findings demonstrated NYT effectively treats neuropathic pain, suggesting that a NYT-induced decrease in blood BDNF contributed to the mechanism of pain relief. In addition, the variation of corticosterone was observed, suggesting that normalization of responsiveness to stress by NYT contributed to the pain relief.

Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain

2018 ◽  
Vol 89 (10) ◽  
pp. 1082-1087 ◽  
Author(s):  
Keisuke Watanabe ◽  
Shigeki Hirano ◽  
Kazuho Kojima ◽  
Kengo Nagashima ◽  
Hiroki Mukai ◽  
...  
Keyword(s):  
Blood Flow ◽  
Neuropathic Pain ◽  
Cerebral Blood Flow ◽  
Pain Relief ◽  
Anterior Cingulate Cortex ◽  
Rating Scale ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Pharmacological Intervention ◽  
Emission Computed Tomography

ObjectiveTo assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy.MethodsUsing iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine.ResultsIMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale.ConclusionsOur results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention.Trial registration numberUMIN000017130;Results.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Chang Ju Hwang ◽  
Jae Hyup Lee ◽  
Jung-Hoon Kim ◽  
Sang Hyuk Min ◽  
Kun-Woo Park ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Pain Relief ◽  
Rating Scale ◽  
Intensity Difference ◽  
Transdermal Fentanyl ◽  
Primary Analysis ◽  
Chronic Neuropathic Pain ◽  
Noninferiority Trial ◽  
Parallel Group ◽  
Significant Difference

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.

Placebo responses in patients with peripheral neuropathic pain

2014 ◽  
Vol 5 (3) ◽  
pp. 210-210 ◽  
Author(s):  
Karen Lund ◽  
Dyveke T. Demant ◽  
Lene Vase ◽  
Søren H. Sindrup ◽  
Troels S. Jensen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Pain Relief ◽  
Pain Intensity ◽  
Positive Emotions ◽  
Rating Scale ◽  
Placebo Treatment ◽  
Peripheral Neuropathic Pain ◽  
Explanatory Variables ◽  
Anxiety Depression

Abstract Background and aim Treatment responses during placebo periods in randomized clinical trials (RCTs) are quite often substantial and may impede a positive outcome of the trial. It would therefore be beneficial to gain more knowledge on factors contributing to large placebo responses in RCTs. The aim of the current study was to identify predictors of placebo responses in patients with peripheral neuropathic pain. Hypotheses We hypothesized that a high baseline pain intensity and variability will be predictive of large responses during placebo treatment. Furthermore, we hypothesized that expectation for pain relief, few prior treatments and side effects, low scores of pain catastrophizing, anxiety, depression and the personality trait neuroticism and high levels of positive emotions will be predictors of placebo responses. Methods This study is part of a randomized, double-blind, placebo-controlled, crossover study with the anticonvulsant oxcarbazepine. Pain intensity was registered at baseline and during treatment periods on a numerical rating scale (NRS, 0–10) along with expectation for pain relief (NRS), psychological measures (scores for anxiety, depression, catastrophizing, neuroticism, and positive emotions), prior treatments, and side effects. Results Multiple regression analysis with pain reduction during placebo treatment as the dependent variable and baseline pain, age, gender, and pain duration as explanatory variables was highly significant (R-squared = 0.53, p < 0.001), while other explanatory variables did not reach statistical significance. Further analyses will be carried out. Conclusions Age and gender were not significant predictors of placebo responses in this study. Further results will be presented at the congress. Acknowledgements This study is part of the Innovative Medicines Initiative project EUROPAIN, www.imi.europa.eu.

Comparing the efficacy of nebulized morphine with intravenous morphine in traumatic musculoskeletal pain management

2020 ◽  
Vol 8 (1) ◽  
pp. 21-21
Author(s):  
Mani Mofidi ◽  
Ali Dashti ◽  
Mahdi Rezai ◽  
Niloufar Ghodrati ◽  
Hoorolnesa Ameli ◽  
...  
Keyword(s):  
Pain Management ◽  
Pain Relief ◽  
Musculoskeletal Pain ◽  
Normal Saline ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Vital Signs ◽  
Categorical Variables ◽  
Intravenous Morphine ◽  
Numerical Rating

Introduction: This study was designed to compare the effectiveness of intravenous morphine with nebulized morphine in pain relief of patients referring to the emergency setting with traumatic musculoskeletal pain. Methods: This randomized, placebo-controlled and double-blind clinical study evaluated 160 patients 18 to 65 years of age with acute traumatic pain, who attended the emergency department during 2019. Subjects were assessed with Numerical Rating Scale based on inclusion and exclusion criteria and randomly divided into two groups. In one group, 80 patients received IV morphine (0.1 mg/kg+5 mL normal saline) plus an equivalent volume of IV placebo. In the second group, 80 patients received nebulized morphine (0.2 mg/kg+5 mL normal saline) plus nebulized placebo. Pain score was monitored in all patients with Numerical Rating Scale before and after intervention at baseline, 15, 30, 45, and 60-minute intervals. Patients’ vital signs and possible adverse events were evaluated in each observation time points. Finally, all participants were assessed for their satisfaction with pain management. Data were analyzed using repeated measure analysis for continuous variables and Binomial test for categorical variables Results: There was no significant difference between the demographic characteristics of patients in study groups. Pain relief between the two groups was similar during the observation (0, 15, 30, 45, 60 min) (P>0.05). There were no changes in vital signs between two groups, although the nebulized group had lower systolic blood pressure at the time-point of 15 minutes after the treatment initiation (P=0.03). Conclusion: Although Nebulized morphine has similar efficacy in comparison with IV route, nebulization might be considered as the clinically efficacious route of morphine administration with minimal side effects, providing optimal pain relief in patients.

scholarly journals The Role of Past Suicidal Behavior on Current Suicidality: A Retrospective Study in the Israeli Military

2021 ◽  
Vol 18 (2) ◽  
pp. 649
Author(s):  
Leah Shelef ◽  
Jessica M Rabbany ◽  
Peter M Gutierrez ◽  
Ron Kedem ◽  
Ariel Ben Yehuda ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Suicidal Behavior ◽  
Military Service ◽  
Suicide Ideation ◽  
Rating Scale ◽  
Suicide Attempts ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Severity Rating ◽  
Significant Difference

Past suicide attempts are a significant risk factor for future suicidality. Therefore, the present military-based study examined the past suicidal behavior of soldiers who recently made a severe suicide attempt. Our sample consisted of 65 active-duty soldiers (61.5% males), between the ages of 18 and 28 years old (M = 20.4, SD ± 1.3). The inclusion criterion was a recent severe suicide attempt, requiring at least a 24 h hospitalization. This sample was divided into two groups, according to previous suicidal behavior, namely whether their first suicide attempt was before or after enlistment (n = 25; 38.5% and n = 40; 61.5%, respectively). We then examined the lethality and intent of the recent event in regard to this division. Four measures were used to assess the subjects’ suicidal characteristics: the Columbia Suicide Severity Rating Scale, the Self-Harm Behavior Questionnaire, the Suicidal Behaviors Questionnaire-Revised, and the Beck Scale for Suicide Ideation. No significant difference in the severity of the suicide attempts (either actual or potential severity) were found between those who had suicide attempts before enlistment and those who had their first attempt in the service. As a matter of fact, most of the suicide attempts that occurred for the first time during military service had used a violent method (58.3%, n = 21). Finally, using multivariate analyses, we found that current thoughts and behavior, rather than past suicidality, was the strongest predictor for the lethality of suicide attempts.

scholarly journals Differential response to scrambler therapy by neuropathic pain phenotypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young Gi Min ◽  
Hyun Seok Baek ◽  
Kyoung-Min Lee ◽  
Yoon-Ho Hong
Keyword(s):  
Neuropathic Pain ◽  
Treatment Outcome ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Brief Pain Inventory ◽  
Differential Response ◽  
Open Label ◽  
Numerical Rating ◽  
Scrambler Therapy ◽  
Post Hoc

AbstractScrambler therapy is a noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory (NPSI) profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, − 15%; 95% CI − 28% to − 2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering based on the NPSI profiles partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the neuropathic pain phenotypes, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.

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