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.

scholarly journals Offset Analgesia in Neuropathic Pain Patients and Effect of Treatment with Morphine and Ketamine

2011 ◽  
Vol 115 (5) ◽  
pp. 1063-1071 ◽  
Author(s):  
Marieke Niesters ◽  
Elske Hoitsma ◽  
Elise Sarton ◽  
Leon Aarts ◽  
Albert Dahan
Keyword(s):  
Neuropathic Pain ◽  
Pain Score ◽  
Pain Perception ◽  
Spontaneous Pain ◽  
Noxious Heat ◽  
Convenience Sample ◽  
Pain Scores ◽  
Effect Of Treatment ◽  
Age Range ◽  
Pain Patients

Background Offset analgesia, in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation, has not been described previously in patients with chronic pain. Methods Offset analgesia responses in 10 patients with neuropathic pain (in both legs) were compared with 10 matched healthy controls and volunteers from a convenience sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by the reduction in electronic pain score upon the 1°C decrease in noxious heat stimulus relative to the peak pain score where pain was administered at the volar side of the arm. Results Offset analgesia was present in healthy volunteers irrespective of age and sex (pain score decrease = 97 ± 1% [mean ± SEM]). In contrast, a reduced or absent offset analgesia response was observed in patients with neuropathic pain (pain score decrease = 56 ± 9% vs. controls 98 ± 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo had no effect on offset analgesia in patients, despite sharp reductions in spontaneous pain scores. Conclusions These data indicate that offset analgesia is fully developed at the age of 6 yr and does not undergo additional maturation. The reduced or absent responses observed in patients with chronic neuropathic pain indicate the inability to modulate changes in pain stimulation, with perseverance of pain perception in situations in which healthy subjects display signs of strong analgesia. Both central and peripheral sites may be involved in the altered offset analgesia responses in these patients.

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 TNFR2 promotes Treg-mediated recovery from neuropathic pain across sexes

2019 ◽  
Vol 116 (34) ◽  
pp. 17045-17050 ◽  
Author(s):  
Roman Fischer ◽  
Maksim Sendetski ◽  
Tania del Rivero ◽  
George F. Martinez ◽  
Valerie Bracchi-Ricard ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Immune Modulation ◽  
Chronic Constriction Injury ◽  
Tumor Necrosis Factor Receptor ◽  
Spontaneous Pain ◽  
Neuronal Regeneration ◽  
Chronic Neuropathic Pain ◽  
Genetic Deletion ◽  
Necrosis Factor

Tumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that is linked to immune modulation and tissue regeneration. Here, we show that TNFR2 essentially promotes long-term pain resolution independently of sex. Genetic deletion of TNFR2 resulted in impaired neuronal regeneration and chronic nonresolving pain after chronic constriction injury (CCI). Further, pharmacological activation of TNFR2 using the TNFR2 agonist EHD2-sc-mTNFR2 in mice with chronic neuropathic pain promoted long-lasting pain recovery. TNFR2 agonist treatment reduced neuronal injury, alleviated peripheral and central inflammation, and promoted repolarization of central nervous system (CNS)-infiltrating myeloid cells into an antiinflammatory/reparative phenotype. Depletion of regulatory T cells (Tregs) delayed spontaneous pain recovery and abolished the therapeutic effect of EHD2-sc-mTNFR2. This study therefore reveals a function of TNFR2 in neuropathic pain recovery and demonstrates that both TNFR2 signaling and Tregs are essential for pain recovery after CCI. Therefore, therapeutic strategies based on the concept of enhancing TNFR2 signaling could be developed into a nonopioid therapy for the treatment of chronic neuropathic pain.

Age-Dependent Development Of Chronic Neuropathic Pain, Allodynia and Sensory Recovery after Upper Limb Nerve Injury in Children

2008 ◽  
Vol 33 (2) ◽  
pp. 186-191 ◽  
Author(s):  
DUNCAN D ATHERTON ◽  
OMEED TAHERZADEH ◽  
DAVID ELLIOT ◽  
PRAVEEN ANAND
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Upper Limb ◽  
Spontaneous Pain ◽  
Sensory Threshold ◽  
Chronic Neuropathic Pain ◽  
Pain Syndromes ◽  
Sensory Recovery ◽  
Pain Symptoms

Forty-nine children with distal upper limb nerve injury were studied at a mean follow-up of 2 years 3 months. Patients who were aged 5 years or younger at the time of nerve injury (15/49) had no chronic neuropathic pain symptoms or allodynia. Patients with allodynia on quantitative sensory testing but no spontaneous pain (8/49) were all older than 5 years and those reporting spontaneous chronic neuropathic pain (5/49) were all older than 12 years at the time of injury. Previous studies of adults with similar nerve injuries report chronic hyperaesthesia in up to 40% of cases. Semmes–Weinstein monofilament testing showed a positive correlation between age at injury and abnormal sensory threshold ( r = 0.60, P<0.0001). These findings indicate that young children show better sensory recovery and are less likely to develop long-term chronic neuropathic pain syndromes than adults following nerve injury.

Nabiximols in chronic neuropathic pain: a meta-analysis of randomized placebo-controlled trials

Pain Medicine ◽  
2021 ◽  
Author(s):  
Igor Dykukha ◽  
Rolf Malessa ◽  
Ute Essner ◽  
Michael A Überall
Keyword(s):  
Neuropathic Pain ◽  
Pain Score ◽  
Rating Scales ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Sensitivity Analyses ◽  
Chronic Neuropathic Pain ◽  
Randomized Controlled Studies ◽  
Small Effect Size

Abstract Objective Pooled analysis of nabiximols and placebo in randomized controlled studies (RCTs) of chronic neuropathic pain. Design Systematic review and meta-analysis. Methods A systematic literature search was conducted to identify double-blind placebo-controlled RCTs of nabiximols for chronic neuropathic pain. The clinical endpoint of interest was change from baseline in mean pain score on 11-point numerical rating scales. Mean difference (MD) and standardized mean difference (SMD, Hedges’ g) were calculated using fixed effect (FE) and random effects (RE) models. Strength of evidence was assessed using the Cochrane Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2). Results Nine RCTs with 1289 participants were included. Quality of evidence (GRADE) was moderate. One study had a high risk of bias (RoB 2) and five had some concerns. For the pooled endpoint of change from baseline in mean pain score, nabiximols was superior to placebo, with a MD of − 0.40 (95% confidence interval [CI]: −0.59 to − 0.21; FE, p &lt; 0.0001) or − 0.44 (95% CI: −0.70 to − 0.19; RE, p = 0.0006). A SMD of − 0.21 (95% CI: −0.32 to − 0.10; FE) or − 0.26 (95% CI: −0.42 to − 0.10; RE) indicated an incremental benefit over background analgesia. Results in favor of nabiximols were maintained in sensitivity analyses. Conclusions Nabiximols was superior to placebo for reduction of chronic neuropathic pain, with a small effect size. Larger RCTs designed to assess the effect of nabiximols in neuropathic pain are required to reach more definitive conclusions.

scholarly journals Cannabidivarin for the treatment of HIV-associated neuropathic pain: a randomized, blinded, controlled clinical trial

2019 ◽  
Author(s):  
Luca Eibach ◽  
Simone Scheffel ◽  
Madeleine Cardebring ◽  
Marie Lettau ◽  
Ozgur Celik ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Neuropathic Pain ◽  
Pain Intensity ◽  
Rating Scale ◽  
Neurological Complication ◽  
Receptor Activation ◽  
Pain Medication ◽  
Controlled Clinical Trial ◽  
Pain Characteristics

Background: HIV remains a major burden to the health care system and neuropathic pain is the most common neurological complication of HIV-infection. Since current treatment strategies often lack satisfying pain relief, cannabinoids are discussed as a new option. We investigated Cannabidivarin as treatment for HIV-associated neuropathic pain. Methods: We conducted a randomized, double-blind, placebo-controlled cross-over study. Patients underwent two successive treatment phases (4 weeks each) and were treated with Cannabidivarin (400mg/d) or placebo in a randomized order. A 3-week wash-out phase was designed to eliminate potential carry-overeffects and patients were followed up for 3 weeks after the end of the second treatment phase. The primary endpoint was pain intensity on an 11-point numeric rating scale and was recorded in a diary. Secondary endpoints were additional pain medication, pain characteristics and quality of life. Results: We included 32 (31 male) patients. The mean pain intensity under Cannabidivarin was by 0.62 points higher compared to placebo (p=0.16; 95% CI -0.27 to 1.51). Cannabidivarin did not influence the amount of additional pain medication, pain characteristics or quality of life. No suspected unexpected adverse reactions occurred during the trial. Discussion: Cannabidivarin was safe but failed to reduce neuropathic pain intensity in HIV-patients. This may be explained by a lack of cannabinoid receptor activation, as indicated by preclinical experiments. Further studies on larger sample sizes are needed.

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 &lt; 0.0001; sub-epidermal nerve fibres [SENFs]; p =&lt; 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 8% Capsaicin Patch in Treatment of Peripheral Neuropathic Pain

2020 ◽  
Vol 5;23 (9;5) ◽  
pp. E541-E548
Author(s):  
Décia Gonçalves
Keyword(s):  
Neuropathic Pain ◽  
Pain Intensity ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Pain Syndrome ◽  
Peripheral Neuropathic Pain ◽  
Patch Application ◽  
Analgesic Therapy ◽  
Number Of Patients ◽  
Painful Area

Background: Neuropathic pain is a complex condition that is difficult to control and has a high impact on quality of life. 8% Capsaicin patch can be a therapeutic strategy in the treatment of peripheral neuropathic pain. Objectives: This study aims to (1) evaluate clinical efficacy and (2) tolerability of 8% capsaicin patch in a Pain Unit. Study Design: Retrospective observational study Setting: Portuguese Pain Unit Methods: A sample of 120 patients diagnosed with peripheral neuropathic pain, underwent treatment with the 8% capsaicin patch between February 2011 and February 2019 in a Portuguese Pain Unit. Patients were included in one of the following groups according to the etiology of pain: postherpetic neuralgia (PHN), chronic post-surgical pain (CPSP), post traumatic neuropathic pain (PTNP), diabetic neuropathy (DN), regional pain syndrome. complex I and II (CRPS I / II), HIVassociated neuropathy (HIVN), lumbar neuropathic pain (LNP), trigeminal neuralgia (TN) and other neuropathies (O). The evaluated parameters were: pain intensity according to unit protocol (numerical rating scale), pain characteristics, location, size of the painful area. The evolution of pain intensity after treatment (patients were considered as responders to therapy if the decrease in NRS was equal to or greater than 30%; patients with a decrease in NRS of 50% or more were also analyzed), the area of pain and the need for adjuvant analgesic therapy, as well as the tolerability to treatment and the identification of eventual predictors of its efficacy were evaluated, at 15 days, 8 weeks and 12 weeks after 8% capsaicin patch. Results: Of the 120 patients in the sample, 40.8% had a ≥ 30% decrease in basal pain intensity 15 days after treatment, 43.3% after 8 weeks and 45.0% after 12 weeks. 30.8% of patients had ≥ 50% decreased basal pain intensity 15 days after treatment, 27.5% after 8 weeks and 30.0% after 12 weeks. Pain area decreased in 36.7% of patients and 18.3% reduced chronic analgesic therapy within 12 weeks after 8% capsaicin patch application. There was only one case of intolerance to the treatment. Limitations: This study has the limitations inherent to a retrospective study. The study period was only 12 weeks and some diagnostic groups included a small number of patients. Conclusion: Treatment of peripheral neuropathic pain with 8% capsaicin patch seem to be effective in the short and medium term, both in decreasing pain intensity and in reducing the painful area. Its application is tolerated by most patients. Key words: 8% capsaicin patch, peripheral neuropathic pain, pain intensity, painful area

scholarly journals Characterization of  self-anticipated surgical pain prior to general anesthesia - a prospective observational study

2021 ◽  
Author(s):  
Wei-Shu Chang ◽  
Yi-Ting Hsieh ◽  
Moa-Chu Chen ◽  
Shu-Ching Chang ◽  
Tzu-Shan Chen ◽  
...  
Keyword(s):  
Pain Management ◽  
Postoperative Pain ◽  
Observational Study ◽  
General Anesthesia ◽  
Pain Intensity ◽  
Pain Score ◽  
Prospective Observational Study ◽  
Rating Scale ◽  
Perioperative Period ◽  
Pain Scores

Abstract Background: Current postoperative pain management principles are primarily based on the type and extent of surgical interventions. This clinical study measured patient’s self-anticipated pain score before surgery and compared the scores with the pain levels and analgesic requirements after surgery.Methods: This prospective observational study recruited consecutive patients who received general anesthesia for elective surgeries in E-Da Hospital (Taiwan) between June and August 2018. Patients were asked to subjectively rate their highest anticipated pain level (numerical rating scale, NRS 0-10) for their scheduled surgical intervention during their preoperative anesthesia assessment. After the operation, the actual pain intensity (NRS 0-10) experienced by the patient in the post-anesthesia care unit (PACU) and the total dose of opioids administered during the perioperative period were recorded. Pain scores ³4 on the NRS were regarded as being unacceptable levels of anticipated or postoperative pain.Results: A total of 857 patients were included in the study. The final database included 49.2% males, and 73.7% of them have had previous operations. The mean anticipated pain score was 4.9±2.5 and 72.2% of the patients reported an anticipated NRS ³4 before their operations. Females anticipated significantly higher overall pain intensities than male patients (adjusted odds ratio 1.695, 95% confidence interval 1.252-2.295; P=0.001). Patients over 40 years of age reported significantly lower overall anticipated NRS scores (4.78±2.49 vs 5.36±2.50; P=0.003). Patients scheduled to receive more invasive surgical procedures were more likely to anticipate high pain intensity in the preoperative period (P<0.001). Higher anticipated pain scores (preoperative NRS³4) were associated with higher actual postoperative pain levels (P=0.032) in the PACU and higher total equivalent opioid use (P=0.001) for acute pain management during the perioperative period.Conclusion: This observational study found that females, younger patients (£40 years), and patients scheduled for more invasive surgeries anticipate significantly higher surgery-related pain. Therefore, appropriate preoperative counseling for analgesic control and management of exaggerated pain expectation in these patients are necessary to improve the quality of anesthesia delivered and patient’s satisfaction.

scholarly journals Beta Electroencephalographic Oscillation Is a Potential GABAergic Biomarker of Chronic Peripheral Neuropathic Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Micael Teixeira ◽  
Christian Mancini ◽  
Corentin Aurèle Wicht ◽  
Gianluca Maestretti ◽  
Thierry Kuntzer ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Power Spectrum ◽  
Pain Intensity ◽  
Visual Analog Scale ◽  
Preliminary Investigation ◽  
Depression Scale ◽  
Analog Scale ◽  
Chronic Neuropathic Pain ◽  
Global Power ◽  
Pain Visual Analog Scale

This preliminary investigation aimed to assess beta (β) oscillation, a marker of the brain GABAergic signaling, as a potential objective pain marker, hence contributing at the same time to the mechanistic approach of pain management. This case–control observational study measured β electroencephalographic (EEG) oscillation in 12 right-handed adult male with chronic neuropathic pain and 10 matched controls (∼55 years). Participants were submitted to clinical evaluation (pain visual analog scale, Hospital Anxiety, and Depression scale) and a 24-min high-density EEG recording (BIOSEMI). Data were analyzed using the EEGlab toolbox (MATLAB), SPSS, and R. The global power spectrum computed within the low (Lβ, 13–20 Hz) and the high (Hβ, 20–30 Hz) β frequency sub-bands was significantly lower in patients than in controls, and accordingly, Lβ was negatively correlated to the pain visual analog scale (R = −0.931, p = 0.007), whereas Hβ correlation was at the edge of significance (R = −0.805; p = 0.053). Patients’ anxiety was correlated to pain intensity (R = 0.755; p = 0.003). Normalization of the low and high β global power spectrum (GPS) to the GPS of the full frequency range, while confirming the significant Lβ power decrease in chronic neuropathic pain patients, vanished the significance of the Hβ decrease, as well as the correlation between Lβ power and pain intensity. Our results suggest that the GABAergic Lβ EEG oscillation is affected by chronic neuropathic pain. Confirming the Lβ GPS decrease and the correlation with pain intensity in larger studies would open new opportunities for the clinical application of gamma-aminobutyric acid-modifying therapies.

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