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Objective To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). Design Retrospective Setting Tertiary hospital single-center Subjects Patients who underwent TSGB receiving KIT or SCS within a 3-year window. Methods Positive TSGB outcomes were defined as ≥2 0–10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥2 NRS score reduction at 2–4 weeks post-KIT and ≥4 NRS score reduction at 2–4 weeks post-SCS implantation, respectively. Results Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n  = 20) reported a ≥ 2 0–10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n  = 14) KIT responders, significantly higher than that in 30.8% (n  = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26–39.02). Among 32 patients who underwent SCS implantation, 68.8% (n  = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n  = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. Conclusions A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS. [ABSTRACT FROM AUTHOR]

Study objective We report a novel block technique aimed to provide lumbosacral, abdominal, and hip analgesia: The quadro-iliac plane (QIP) block. Design A cadaveric examination that evaluates the spread of QIP block. Setting Cadaver laboratory. Patients One unembalmed cadaver. Interventions Bilateral ultrasound-guided QIP blocks on cadavers with 40 mL of methylene blue %0.5 each side. Measurements Dye spread in cadaver. Main results There was staining in the deep interfascial plane of the erector spinae muscles. Extensive staining of the interfascial plane corresponding to the posterior aspect of the quadratus lumborum muscle (QLM) was observed. There was extensive staining on the anterior surface of the QLM. There was spread of dye traversing along the transversalis fascia and significantly infiltrating retroperitoneal fat tissue. Bilateral staining of the ilioinguinal and iliohypogastric nerves was observed. On the right, there was minimal staining over the subcostal nerve. There was dye present bilaterally within the deep regions of the transverse processes. The lumbar plexus was stained on both sides. Conclusion The local anesthetic applied from a place where the QLM reaches its largest volume and the fascial plane creates a closed gap in the caudal area may exhibit a more rounded and extensive spread. Quadro-iliac plane block, involves the administration of local anesthetic to the posterior aspect of the QLM at its origin from the iliac crest. According to our cadaver study, this technique may be a promising option for alleviating acute and chronic pain in the lumbosacral, lower abdominal, and hip regions. [ABSTRACT FROM AUTHOR]

Objective As psychologically based interventions have been shown to have clinical utility for adults with chronic pain generally, a similar benefit might be expected in the management of chronic neuropathic pain (NeuP). However, to date, this has not been established, with existing systematic reviews on this topic being hampered by the scarcity of randomized controlled trials (RCTs). This review aimed to identify the type of psychologically based interventions studied for adults with chronic NeuP. It also aimed to assess whether there are enough RCTs to justify undertaking an updated systematic review. Methods Seven databases and 2 clinical trial registries were searched for NeuP and psychologically based interventions from database inception to December 2021, and the search was updated in February 2023. The search was broadened by reviewing the reference list of included studies and contacting field experts. Predetermined study characteristics were extracted. Results Of 4682 records screened, 33 articles (less than 1%) met the eligibility criteria. Four broad intervention approaches were observed, including cognitive-behavioral approaches (n  = 16), mindfulness/meditation (n  = 10), trauma-focused therapy (n  = 4), and hypnosis (n  = 3). Thirteen RCTs were identified, and of these, 9 retained 20 participants in each arm after treatment. Conclusions Cognitive-behavioral therapy was the most common therapeutic approach identified, whereas mindfulness/meditation was the most frequently used technique. Almost half to two-thirds of the studies reported significant improvements in pain, disability, or distress, which suggests that psychologically based interventions are potentially beneficial for adults with chronic NeuP. An updated systematic review seems warranted. Study registration Open Science Framework (https://osf.io) (December 6, 2021; DOI: 10.17605/OSF.IO/WNSTM). [ABSTRACT FROM AUTHOR]

Objective Although the presence of neuropathic pain (NP) components has been reported in whiplash-associated disorders (WAD), no studies have analyzed the usefulness of NP screening questionnaires to detect NP components in WAD. This study aimed to assess the usefulness of 3 NP screening tools (Douleur Neuropathique 4 [DN4], self-administered Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS], and painDETECT questionnaire [PDQ]) to detect the presence of NP components in acute WAD. Design A cross-sectional study. Setting Hospital. Subjects Of 188 eligible individuals, 50 people (68% women, mean age = 40.3 ± 12.5 years) with acute WAD (52% Grade III) were included. Methods Specialized physicians initially screened participants for the presence of NP components according to clinical practice and international recommendations. After physician assessment, blinded investigators used NP screening questionnaires (DN4, S-LANSS, and PDQ) to assess participants within 2 weeks of their accident. The diagnostic accuracy of these tools was analyzed and compared with the reference standard (physicians' assessments). Results The 3 screening questionnaires showed excellent discriminant validity (area under the curve: ≥0.8), especially S-LANSS (area under the curve: 0.9; P  < .001). DN4 demonstrated the highest sensitivity (87%), followed by S-LANSS (75%), while S-LANSS and PDQ showed the highest specificity (85% and 82%, respectively). These tools demonstrated a strong correlation with the reference standard (S-LANSS: rho = 0.7; PDQ: rho = 0.62; DN4: rho = 0.7; all, P  < .001). Conclusions The DN4, S-LANSS, and PDQ show excellent discriminant validity to detect the presence of NP components in acute WAD, especially S-LANSS. Initial screening with these tools might improve management of WAD. [ABSTRACT FROM AUTHOR]

Background The aims of this study were to (1) evaluate the time between onset of occipital neuralgia symptoms and nerve decompression surgery, (2) perform a cost comparison analysis between surgical and nonsurgical treatment of occipital neuralgia, and (3) report postoperative results of nerve decompression for occipital neuralgia. Methods Subjects (n  = 1112) who underwent screening for nerve decompression surgery were evaluated for occipital neuralgia. Of those, 367 patients (33%) met the inclusion criteria. Timing of occipital neuralgia symptom onset and pain characteristics were prospectively collected. Cost associated with the nonsurgical treatment of occipital neuralgia was calculated for the period between onset of symptoms and surgery. Results A total of 226 patients (73%) underwent occipital nerve decompression. The average time between onset of occipital neuralgia and surgery was 19 years (7.1–32). Postoperatively, the median number of pain days per month decreased by 17 (0–26, 57%) (P  < .001), the median pain intensity decreased by 4 (2–8, 44%) (P  < .001), and median pain duration in hours was reduced by 12 (2–23, 50%) (P  < .001). The annual mean cost of nonsurgical occipital neuralgia treatment was $28 728.82 ($16 419.42–$41 198.41) per patient. The mean cost during the 19-year time frame before surgery was $545 847.75($311 968.90–$782 769.82). Conclusion This study demonstrates that patients suffer from occipital neuralgia for an average of 19 years before undergoing surgery. Nerve decompression reduces symptom severity significantly and should be considered earlier in the treatment course of occipital neuralgia that is refractory to conservative treatment to prevent patient morbidity and decrease direct and indirect health care costs. [ABSTRACT FROM AUTHOR]

Objective This case series retrospectively reviewed the outcomes in patients implanted with combined, synchronous dorsal root ganglion stimulation (DRGS) and spinal cord stimulation (SCS) connected to a single implantable pulse generator (IPG) in a tertiary referral neuromodulation centre in the United Kingdom. Methods Twenty-six patients underwent a trial of DRGS+SCS for treating focal neuropathic pain between January 2016 and December 2019, with a follow-up in February 2022. A Transgrade approach was employed for DRGS. Patients were provided with 3 possible stimulation programs: DRGS-only, SCS-only, or DRGS+SCS. Patients were assessed for pain intensity, patients' global impression of change (PGIC), preferred lead(s) and complications. Results Twenty patients were successful and went on for full implantation. The most common diagnosis was Complex Regional Pain Syndrome. After an average of 3.1 years follow-up, 1 patient was lost to follow-up, and 2 were non-responders. Of the remaining 17 patients, 16 (94%) continued to report a PGIC of 7. The average pain intensity at Baseline was 8.5 on an NRS scale of 0–10. At the last follow-up, the average NRS reduction overall was 78.9% with no statistical difference between those preferring DRGS+SCS (n  = 9), SCS-only (n  = 3) and DRGS-only (n  = 5). The combination of DRGS+SCS was preferred by 53% at the last follow-up. There were no serious neurological complications. Conclusions This retrospective case series demonstrates the potential effectiveness of combined DRGS+SCS with sustained analgesia observed at an average follow-up of over 3 years. Implanting combined DRGS+SCS may provide programming flexibility and therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Introduction Neuropathic pain encompasses multiple diagnoses with detrimental impacts on quality of life and overall health. In older adults, pharmacological management is limited by adverse effects and drug interactions, while surgical management involves perioperative risk. Prior reviews addressing non-pharmacological interventions for neuropathic pain have not focused on this demographic. Therefore, this systematic review synthesizes the evidence regarding the effectiveness of non-pharmacological interventions in reducing neuropathic pain severity in older adults. Methods PubMed, CINAHL, Web of Science, and PsycInfo were searched using key terms, with inclusion criteria of age ≥ 65, neuropathic pain, non-pharmacological intervention, pain severity measurement, English language, peer-reviewed, and either randomized controlled trial (RCT) or quasi-experimental design. In total, 2759 records were identified, with an additional 28 records identified by review of reference lists. After removal of duplicates, 2288 records were screened by title and abstract, 404 full-text articles were assessed, and 19 articles were critically reviewed and synthesized. Results Of the 14 RCTs and 5 quasi-experimental studies included in the review, the most common intervention was electric and/or magnetic therapy, followed by acupuncture, mindfulness meditation, exercise, and light therapy. Several studies revealed both statistical and clinical significance, but conclusions were limited by small sample sizes and methodological shortcomings. The interventions were generally safe and acceptable. Conclusions Results should be interpreted with consideration of clinical vs statistical significance, mediators of pain severity, and individual variations in effectiveness. Further research should address multimodal and novel interventions, newer models of care, and technology-based interventions. [ABSTRACT FROM AUTHOR]

ObjectiveDistal sensory polyneuropathy (DSP) is a disabling consequence of human immunodeficiency virus (HIV), leading to poor quality of life and more frequent falls in older age. Neuropathic pain and paresthesia are prevalent symptoms; however, there are currently no known curative treatments and the longitudinal course of pain in HIV-associated DSP is poorly characterized.MethodsThis was a prospective longitudinal study of 265 people with HIV (PWH) enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study with baseline and 12-year follow-up evaluations. Since pain and paresthesia are highly correlated, statistical decomposition was used to separate the two symptoms at baseline. Multivariable logistic regression analyses of decomposed variables were used to determine the effects of neuropathy symptoms at baseline on presence and worsening of distal neuropathic pain at 12-year follow-up, adjusted for covariates.ResultsMean age was 56 ± 8 years, and 21% were female at follow-up. Nearly the entire cohort (96%) was on antiretroviral therapy (ART), and 82% had suppressed (≤50 copies/mL) plasma viral loads at follow-up. Of those with pain at follow-up (n = 100), 23% had paresthesia at the initial visit. Decomposed paresthesia at baseline increased the risk of pain at follow-up (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.18, 2.07), and decomposed pain at baseline predicted a higher frequency of pain at follow-up (OR 1.96 [95% CI 1.51, 2.58]).ConclusionsParesthesias are a clinically significant predictor of incident pain at follow-up among aging PWH with DSP. Development of new therapies to encourage neuroregeneration might take advantage of this finding to choose individuals likely to benefit from treatment preventing incident pain.

Objective Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia. Study design Randomized, controlled, double-blind cross-over Setting Clinical research unit Subjects Individuals aged 18 to 70 years with neuropathic pain for at least 6 months. Methods Individuals received intrathecal injections of oxytocin and saline, separated by at least 7 days, and ongoing pain in neuropathic area (VAS [visual analog scale]) and areas of hypersensitivity to von Frey filament and cotton wisp brushing were measured for 4 hours. Primary outcome was VAS pain in the first 4 hours after injection, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at daily intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hours after injections. Results The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87 and 2.49 ± 0.87, respectively (P  = .003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ± 0.89; P  = .001). Allodynic area decreased by 11%, but hyperalgesic area increased by 18% after oxytocin compared to placebo. There were no study drug related adverse effects. Conclusion Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted. Trial registration This study was registered at ClinicalTrials.gov on 03/27/2014 (NCT02100956). The first subject was studied on 06/25/2014. [ABSTRACT FROM AUTHOR]

Objective Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. Methods Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. Results CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34)  = 4.98, P  < .001, contralateral: t(35) = 3.19, P  = .005, control: t(31) = 2.65, P  = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P  = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P  = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P  = .048). Conclusions Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS. [ABSTRACT FROM AUTHOR]

Objective Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients. Methods Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 1:1 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weeks of treatment in both groups. Duloxetine at doses of 30 mg and similarly appearing placebo tablets were given and the dose was doubled if there was no response at the end of 2 weeks. Response to treatment was defined as ≥2 points reduction of NRS pain score. Results In total, 82 patients were enrolled in the study, 41 in each group. There was a significant difference in reduction in NRS score between duloxetine and placebo group from baseline (6.51 ± 1.03 vs 6.37 ± 1.41) to 4 weeks (3.02 ± 1.70 vs 4.40 ± 1.77, P  = .02 for difference in reduction between groups). SFMPQ-2 score (P  = .032) and Pain Disability Index score (P  = .005) also differ significantly from baseline to 4 weeks between the two groups. PGIC score at the end of 4 weeks was significantly different between the two groups (5.15 ± 1.54 vs 3.89 ± 1.51; P  < .001). Responder rate (defined as % of patients with ≥ 2 points reduction on NRS pain score from baseline to end of 4 weeks), on post hoc analysis was found to be significantly higher in duloxetine group (80.5%) than placebo group (43.9%) (P  = .042). Conclusions Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain. [ABSTRACT FROM AUTHOR]

Ulnar neuropathy is a condition that manifests with symptoms of neuropathic pain, numbness, tingling, and even possible motor deficits in the ulnar distribution of the arm. This debilitating painful condition may be refractory to conservative, pharmacologic, and surgical interventions. Peripheral nerve stimulation (PNS) technology has advanced significantly in recent years allowing for conditions such as ulnar neuropathy to be treated in a minimally invasive manner. Here we report the first case reports in the literature (to our knowledge) of two patients with intractable ulnar neuropathy who underwent minimally invasive PNS Bioventus implants. Both patients experienced at least 75% pain relief based on NRS scores at 6 months after ulnar nerve PNS implantation. The patients also experienced significant improvement in functional outcomes, including return to employment, ability to perform activities of daily living without any impairment, and improved quality of life measures. While the results presented in our two case reports are promising, we only provide observational data over a 6 to 15-month period post-implantation. Future well-powered, large-scale, and long-term randomized controlled trials are warranted to determine efficacy and long-term pain and functional outcomes from PNS therapy for treatment of ulnar neuropathy. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia, considered by many the worst pain that humankind can experience, has been called "the suicide disease." Neuroablative procedures are good options when conservative treatment fails to promote pain relief or in those whose side effects are unbearable. The objective was to compare the effectiveness and safety of trigeminal percutaneous radiofrequency ablation in classical refractory trigeminal neuralgia in a prospective, randomized, double-blind, sham-controlled clinical trial. We included 30 consecutive patients with classical trigeminal neuralgia who had failed to respond to drug treatment. The patients were randomly assigned into two groups: a thermal radiofrequency and a sham group. The thermal radiofrequency group were submitted to a 75°C lesion for 60 seconds after proper sensory and motor stimulation. All steps were carried out in the sham group except the thermal lesion. Patients were evaluated using the Numerical Rating Scale (NRS), the 36-Item Short-Form Health Survey questionnaire, and anticonvulsant dose. After 1 month, the mean NRS score decreased from 9.2 to 0.7 in the radiofrequency group and from 8.9 to 5.8 in the sham group. This significant reduction was measurable starting at day one after the procedure and remained significant throughout the first month. Changing groups was allowed after one month, after which the pain reduction was similar between the two groups. Percutaneous trigeminal radiofrequency ablation results in statistically and clinically significant greater pain relief than the sham procedure after 1 month of follow-up. These results support using radiofrequency nerve ablation as a treatment for refractory trigeminal neuralgia. [ABSTRACT FROM AUTHOR]

Background As a traditional Chinese therapy, acupuncture is proposed worldwide as a treatment for pain and other health problems, but findings on acupuncture analgesia have been inconsistent because of its variable modalities of therapeutic intervention. Objective This study aimed to evaluate the existing animal studies for evidence on acupuncture and its effect on glia in association with a reduction in pain conditions. Methods Literature searches were performed in four English- and Chinese-language databases (Web of Science, PubMed, EMBASE, and CNKI) on October 8, 2021. Included studies reported the pain outcome (e.g. paw withdrawal latency, paw withdrawal threshold) and glia outcome (e.g. glial marker GFPA, Iba1, and OX42) in pain-induced animals during acupuncture treatment. Results Fifty-two preclinical studies were included in the meta-analysis. A single acupuncture treatment in rodents had an analgesic effect, which was more effective in inflammatory pain than in neuropathic pain in the early phase of treatment. The analgesic efficacy became more curative after repeated acupuncture. Furthermore, acupuncture treatment could effectively inhibit the activity of astrocytes and microglia in both inflammatory pain and neuropathic pain in a time-course pattern. Conclusions Acupuncture treatment improves analgesic effect in rodent pain conditions under the possible mechanism of glial inhibition. Therefore, these results provide an opportunity to evaluate the effectiveness of acupuncture analgesia and neuroinflammation in animal models to research further neurobiological mechanisms and to inform the design of future clinical trials. Study registration PROSPERO (ID: CRD42020196011). [ABSTRACT FROM AUTHOR]

Background Neuropathic pain (NP) after spinal cord injury (SCI) exacerbates disability, decreases quality of life (QOL), and is often refractory to available therapies. Patients report willingness to trade potential recovery of strength, bowel, bladder, or sexual function for pain relief. One proposed mechanism causing NP is up-regulation of transient receptor potential vanilloid 1 (TRPV 1) proteins in uninjured C fibers and dorsal root ganglia causing neuronal excitability. Recent studies have found up-regulation of TRPV 1 proteins after SCI. Objective We hypothesize the application of capsaicin 8% patch (C8P), FDA approved for NP in diabetic peripheral neuropathy and post-herpetic neuralgia, will improve pain, function and QOL in persons with SCI. Methods Randomized single-blind crossover design in which 11 persons with SCI and NP refractory to two oral pain medications received C8P or a control low dose Capsaicin 0.025% patch (CON) over two 12-week periods. Pain (VAS, MPI-SCI), quality of life (WHO-QOL), and functional status (SCIM) were measured at 2–4-week intervals. Results There was a main treatment effect of C8P over CON on VAS and MPI-SCI outcomes with pain reduction of 35% and 29% at weeks 2 and 4, respectively. C8P also demonstrated a main treatment effect over CON on the SCIM mobility subscale. WHO-QOL scores did not improve with C8P. Conclusions C8P improves pain and mobility for patients with SCI and refractory NP. Larger studies should be performed to evaluate impact of repeat applications and QOL outcomes. [ABSTRACT FROM AUTHOR]

Objective:To identify factors associated with pain severity and opioid consumption in the early perioperative period. Design:Prospective observational cohort study. Setting:Tertiary academic medical center. Subjects:Patients with osteoarthritis older than age 45 years undergoing primary total knee replacement at Brigham and Women's Hospital. A total of 126 patients enrolled. Methods:Preoperatively, pain questionnaires and quantitative sensory testing were performed on patients to develop a psychosocial and psychophysical profile. Postoperatively, pain scores and opioid consumption were measured as primary end points. Univariate and multiple linear regression analyses were performed to determine the predictive value of these characteristics on perioperative pain scores and opioid consumption. Results:Regression analysis revealed several predictors of acute postoperative pain scores including temporal summation of pain (TSP; P = 0.001), body mass index (BMI; P = 0.044), number of previous knee surgeries (P = 0.006), and female gender (P = 0.023). Similarly, predictors of opioid utilization included TSP (P = 0.011), BMI (P = 0.02), age (P =

Background Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves. Study Design A systematic review of human studies involving the use of injectable biologics for neuropathic pain. Methods A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020. Results The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data. Conclusion According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making. [ABSTRACT FROM AUTHOR]

Objective Currently available treatments for neuropathic pain are only modestly efficacious when assessed in randomized clinical trials and work for only some patients in the clinic. Induced-pain or gain-of-function phenotypes have been shown to predict response to analgesics (vs placebos) in patients with neuropathic pain. However, the predictive value of these phenotypes has never been studied in post-traumatic neuropathic pain. Methods Mixed-effects models for repeated measures were used to evaluate the efficacy of pregabalin vs placebo in subgroups with induced-pain phenotypes (i.e. hyperalgesia or allodynia) in data from a recent, multinational randomized clinical trial (N = 539) that identified phenotypic subgroups through the use of a structured clinical exam. Results The difference in mean pain score between the active and placebo groups (i.e. delta) after 15 weeks of treatment for the subgroup with hyperalgesia was –0.76 (P  = 0.001), compared with 0.19 (P  = 0.47) for the subgroup that did not have hyperalgesia. The treatment-by-phenotype interaction, which tests whether subgroups have statistically different treatment responses, was significant (P  = 0.0067). The delta for the subgroup with allodynia was –0.31 (P  = 0.22), compared with –0.30 (P  = 0.22) for the subgroup that did not have allodynia (treatment-by-phenotype interaction P  = 0.98). Conclusions These data suggest that hyperalgesia, but not allodynia, predicts response to pregabalin in patients with chronic post-traumatic neuropathic pain. This study extends the growing data supporting the utility of induced-pain phenotypes to predict response to analgesics in post-traumatic neuropathic pain. Sensory phenotyping in large, multisite trials through the use of a structured clinical exam has the potential to accelerate the development of new analgesics and improve the generalizability of clinical trial results. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss the clinical and pathophysiological aspects of spinal cord stimulation (SCS) as a pain management strategy by citing the case of 11 patients with nonpathological spinal cord. Also cited are the use of epidural electrodes in SCS to electrically modulate the circuitry in the spinal cord, and the potential autonomic side effects of SCS.

Background Recent studies have suggested that neuropathic pain exhibits a daily diurnal pattern, with peak levels usually occurring in the late afternoon to evening and the trough in the morning hours, although literature on this topic has been sparse. This scoping review examines current evidence on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain. Methods A literature search was conducted in major medical databases for relevant articles on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain. Data extracted included details of specific animal models or specific neuropathic pain conditions in humans, methods and timing of assessing pain severity, and specific findings of diurnal variation in pain intensity or its surrogate markers. Results Thirteen animal and eight human studies published between 1976 and 2020 were included in the analysis. Seven of the 13 animal studies reported specific diurnal variation in pain intensity, with five of the seven studies reporting a trend toward increased sensitivity to mechanical allodynia or thermal hyperalgesia in the late light to dark phase. All eight studies in human subjects reported a diurnal variation in the intensity of neuropathic pain, where there was an increase in pain intensity through the day with peaks in the late evening and early night hours. Conclusions Studies included in this review demonstrated a diurnal variation in the pattern of neuropathic pain that is distinct from the pattern for nociceptive pain. These findings have implications for potential therapeutic strategies for neuropathic pain. [ABSTRACT FROM AUTHOR]

Objective Neuropathic pain is complex and often refractory. Clinical hypnosis has emerged as a viable treatment for pain. This scoping review is the first comprehensive review of hypnosis for chronic neuropathic pain. It critically assesses available evidence noting practice implications, literature gaps, and future research opportunities. Subjects Individuals with chronic neuropathic pain treated with hypnosis. Methods Following PRISMA guidelines, we searched PubMed, CINAHL, Embase, and PsycInfo for studies for which the intervention and primary outcome(s) were associated with hypnosis and neuropathic pain, respectively. Included studies were empirical, in English, and published from January 1996 to August 2021. Results Nine articles with 301 total participants were reviewed. Neuropathic pain included, for example, complex regional pain syndrome (CRPS), brachial neuralgia, and spinal cord injury. Hypnosis dose varied with administration and format. Six studies used comparators. Every trial demonstrated pain and quality-of-life benefits, with several controlled trials indicating hypnosis as superior to active comparator or standard of care. CRPS-specific studies showed notable improvements but had significant study limitations. Methodological weaknesses involved trial design, endpoints, and recruitment strategies. Conclusions The evidence is weak because of poor study design, yet encouraging both for analgesia and functional restoration in hard-to-treat chronic neuropathic pain conditions. We highlight and discuss key knowledge gaps and identify particular diagnoses with promising outcomes after hypnosis treatment. This review illustrates the need for further empirical controlled research regarding hypnosis for chronic neuropathic pain and provides suggestions for future studies. [ABSTRACT FROM AUTHOR]

Objectives To assess risk factors for persistent neuropathic pain in subjects recovered from coronavirus disease 2019 (COVID-19) and to study the serum level of neurofilament light chain (NFL) in those patients. Design Case-control study. Setting Persistent post-COVID-19 pain. Subjects In total, 45 patients with post-COVID-19 pain and another 45 age and sex-matched healthcare workers who recovered from COVID-19 without pain. Methods The included participants were subjected to medical history taking, screening for depressive disorders, comprehensive neurological examination, and pain evaluation using the Douleur Neuropathique en 4 questions (DN4). All patients who had a score at least 4/10 on DN4 were included. The serum NFL level was measured for both groups at the time of patients' enrollment. Results The frequency of depression, moderate and severe COVID-19 cases, disease duration and serum ferritin were significantly higher in the cases with post-COVID-19 pain than controls. Binary logistic regression revealed that depression, azithromycin use, moderate and severe COVID-19 increased the odds of post-COVID-19 pain by 4.462, 5.444, 4.901, and 6.276 times, respectively. Cases with post-COVID-19 pain had significantly higher NFL (11.34 ± 9.7, 95% confidence interval [CI]: 8.42–14.25) than control group (7.64 ± 5.40, 95% CI: 6.02–9.27), (P value = .029). Patients with allodynia had significantly higher NFL (14.96 ± 12.41, 95% CI: 8.58–21.35) compared to those without (9.14 ± 6.99, 95% CI: 6.43–11.85) (P value = .05). Discussion Depression, azithromycin, and moderate and severe COVID-19 are independent predictors of persistent post-COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19. [ABSTRACT FROM AUTHOR]

Objective Oxidative stress plays an important role in neuropathic pain (NP). Spinal manipulative therapy (SMT) can exert beneficial effects on pain outcomes in humans and in animal models. SMT can also modulate oxidative stress markers in both humans and animals. We aimed to determine the effect of Impulse®-assisted SMT (ISMT) on nociception and oxidative stress biomarkers in the spinal cords and sciatic nerves of rats with NP. Methods NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Animals were randomly assigned to naive, sham (rats with sciatic nerve exposure but without ligatures), or CCI, with and without ISMT. ISMT was applied onto the skin area corresponding to the spinous process of L4–L5, three times per week for 2 weeks. Mechanical threshold, latency to paw withdrawal in response to thermal stimulus, and oxidative stress biomarkers in the spinal cord and sciatic nerve were the main outcomes evaluated. Results ISMT significantly increased mechanical threshold and withdrawal latency after CCI. In the spinal cord, ISMT prevented the increase of pro-oxidative superoxide anion generation and hydrogen peroxide levels. Lipid hydroperoxide levels both in the spinal cord and in the sciatic nerve were attenuated by ISMT. Total antioxidant capacity increased in the spinal cords and sciatic nerves of CCI rats with and without ISMT. CCI and ISMT did not significantly change the total thiol content of the spinal cord. Conclusions Our findings suggest that reduced oxidative stress in the spinal cord and/or nerve may be an important mechanism underlying a therapeutic effect of SMT to manage NP nonpharmacologically. [ABSTRACT FROM AUTHOR]

Objective. Despite modern antiretroviral therapy, HIV-associated neuropathy is one of the most prevalent, disabling and treatment-resistant complications of HIV disease. The presence and intensity of distal neuropathic pain is not fully explained by the degree of peripheral nerve damage. A better understanding of brain structure in HIV distal neuropathic pain may help explain why some patients with HIV neuropathy report pain while the majority does not. Previously, we reported that more intense distal neuropathic pain was associated with smaller total cerebral cortical gray matter volumes. The objective of this study was to determine which parts of the cortex are smaller.Methods. HIV positive individuals with and without distal neuropathic pain enrolled in the multisite (N = 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent structural brain magnetic resonance imaging. Voxel-based morphometry was used to investigate regional brain volumes in these structural brain images.Results. Left ventral posterior cingulate cortex was smaller for HIV positive individuals with versus without distal neuropathic pain (peak P  = 0.017; peak t = 5.15; MNI coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray matter structures typically associated with pain processing were also smaller for HIV positive individuals having higher intensity ratings of distal neuropathic pain.Conclusions. The posterior cingulate is thought to be involved in inhibiting the perception of painful stimuli. Mechanistically a smaller posterior cingulate cortex structure may be related to reduced anti-nociception contributing to increased distal neuropathic pain.

Objective To establish the efficacy of medications, incidence of adverse events (AEs), and withdrawal rates associated with the pharmacological management of chronic spinal cord injury pain. Methodology PubMed, MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and PsycINFO were searched (November 2017) and updated (January 2020). Two independent review authors screened and identified papers for inclusion. Results Twenty-one studies met inclusion requirements for efficacy analysis and 17 for AE and withdrawal rate analysis; no additional papers were included from the updated 2020 search. Treatments were divided into six categories: anticonvulsants (n = 6), antidepressants (n = 3), analgesics (n = 8), anti-spasticity medications (n = 2), cannabinoids (n = 1), and other (n = 2). Trials of anticonvulsants, antidepressants, and cannabinoids included long-term follow-up trials (2 weeks to 4 months), and trials of analgesics and anti-spasticity medications, among others, were short-term trials (0–2 days). Effectiveness for neuropathic pain was found for pregabalin (3/3 studies) and lidocaine (2/3 studies). Studies using ketamine also reported effectiveness (2/2), but the quality of these papers was rated as poor. The most frequently reported AEs included dizziness, dry mouth, nausea, and constipation. Pregabalin was associated with a higher risk of somnolence (risk ratio [RR] 3.15, 95% confidence interval [CI]: 2.00–4.98) and dizziness (RR 2.9, 95% CI: 1.58–5.30). Ketamine was associated with a higher risk of reduced vision (RR 9.00, 95% CI: 0.05–146.11), dizziness (RR 8.33, 95% CI: 1.73–40.10), and somnolence (RR 7.00, 95% CI: 1.73–40.1). Withdrawal rates ranged from 18.4% for antidepressants to 0–30% for anticonvulsants, 0–10% for anti-spasticity medications, 0–48% for analgesics, 28.6% for cannabinoids, and 0–22.2% for other medications. Conclusion Pregabalin was found to be effective for neuropathic pain vs placebo. Cannabinoids were ineffective for neuropathic pain. AEs are a common cause for withdrawal. The nature of AEs was poorly reported, and AE reporting should be improved in future randomized controlled trials. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Occipital neuralgia (ON) also known as C2 neuralgia or Arnold's neuralgia. Topics include characterized as unilateral or bilateral paroxysmal shooting or stabbing pain in the posterior part of the scalp; and use of coiled, smaller-gauge, flexible leads associated with significantly fewer infections.

The article discusses research which investigated the association of the development of neuropathic post-COVID pain symptoms with serological biomarkers at hospital admission in COVID-19 survivors. Data shows the laboratory biomarkers of COVID-19 patients according to neuropathic symptoms. It attributes the neuro-invasive potential of the SARS-CoV-2 virus explaining the neuropathic symptoms to the high expression of Angiotensin Converting Enzyme-2 (ACE2) receptors within nervous system cells.

Objective To assess the efficacy and safety of N-acetylcysteine in the treatment of chronic pain. Methods A systematic search was carried out until April 2020 for clinical studies of N-acetylcysteine in the management of any persistent or recurrent chronic pain condition for adults ≥ 18 years old. Risk of bias was assessed using the validated risk of bias tools. When appropriate, a meta-analysis using a random-effects model was performed, with a fixed-effect model for sensitivity analysis. Results Nine studies (n = 863) were included (five randomized controlled trials [RCTs], two open-label non-comparative studies and two comparative studies), that evaluated patients with sickle cell disease (3), complex regional pain syndrome (1), pelvic pain/endometriosis (2), rheumatoid arthritis (1), diabetic neuropathy (1), and chronic neuropathic pain (1). In the pooled analysis of three RCTs, N-acetylcysteine did not reduce pain intensities (SMD −0.21, 95% confidence interval [CI]: −0.33 to 0.75, random-effects), improve functional outcomes (SMD 0.21, 95% CI −0.33 to 0.75) or quality of life (SMD 0.60, 95% CI: −4.44 to 5.64); however, sensitivity analysis with a fixed effect model demonstrated an effect for pain intensities and function. Due to adverse events being inconsistently reported, no conclusion could be made regarding safety of N-acetylcysteine in chronic pain. Conclusions While there is some evidence to indicate N-acetylcysteine may provide analgesic efficacy for certain pain conditions, there is insufficient evidence to provide definitive evidence on NAC in chronic pain management. Larger-size RCTs spanning a variety of chronic pain conditions are needed to determine N-acetylcysteine's role, if any, in pain medicine. [ABSTRACT FROM AUTHOR]

The article presents case study of 52-year-old woman who presented to pain medicine clinic initially in 2012 due to painful lower extremity spasticity and increasing spasms in the upper extremities. It mentions diagnosis of neurosarcoidosis, a multi-organ system granulomatous disease that, when untreated, can cause significant morbidity and mortality.

Objective This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. Design Randomized controlled pilot study. Methods The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. Results A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. Conclusions A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application. Design Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up. Blinding Open-label. Setting Multicenter clinical trial. Subjects STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy. Methods Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment. Results In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction. Conclusions Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders. [ABSTRACT FROM AUTHOR]

Objective About one-third of patients with multiple sclerosis (MS) suffers from chronic and excruciating central neuropathic pain (CNP). The mechanism underlying CNP in MS is not clear, since previous studies are scarce and their results are inconsistent. Our aim was to determine whether CNP in MS is associated with impairment of the spinothalamic-thalamocortical pathways (STTCs) and/or increased excitability of the pain system. Design The study was cross-sectional Setting The study was conducted at a general hospital Participants Participants were 47 MS patients with CNP, 42 MS patients without CNP and 32 healthy controls. Methods Sensory testing included the measurement of temperature, pain, and touch thresholds and the thermal grill illusion for evaluating STTCs function and hyperpathia and allodynia as indicators of hyperexcitability. CNP was characterized using interviews and questionnaires. Results The CNP group had higher cold and warm thresholds (P  < 0.01), as well as higher thermal grill illusion perception thresholds (P  < 0.05), especially in painful body regions compared with controls, whereas touch and pain thresholds values were normal. The CNP group also had a significantly greater prevalence of hyperpathia and allodynia. Regression analysis revealed that whereas presence of CNP was associated with a higher cold threshold, CNP intensity and the number of painful body regions were associated with allodynia and hyperpathia, respectively. Conclusions CNP in MS is characterized by a specific impairment of STTC function, the innocuous thermal pathways, and by pain hyperexcitability. Whereas CNP presence is associated with STTC impairment, its severity and extent are associated with pain hyperexcitability. Interventions that reduce excitability level may therefore mitigate CNP severity. [ABSTRACT FROM AUTHOR]

The article presents Long-Term Results with Adjuvant Ozone Therapy in the Management of Chronic Pelvic Pain Secondary to Cancer Treatment. Topics discussed include Management of local pain after pelvic tumor treatment requires excluding the possibility of tumor relapse and, at the same time, starting analgesic and opioid treatment as needed; and patients with potentially prolonged life expectancy, high doses of opioids are controversial because their long-term safety and effectiveness.

Objectives The treatment for neuropathic pain is still a big challenge. Pulsed radiofrequency technique has been widely used to relieve neuropathic pain in recent years. The purpose of this study is to optimize the temperature for pulsed radiofrequency therapy. Design Animal, experimental study. Methods Seventy-five male SD rats were randomly divided into five groups: Sham operation group (Sham group), chronic constriction injury group (CCI group), PRF 42°C group (P42 group), PRF 50°C group (P50 group), and PRF 60°C group (P60 group). The hindpaw withdrawal threshold (HWT), paw thermal withdrawal latency (PTWL), sciatic nerve structure, and the concentration of spinal methionine enkephalin(M-ENK) were detected to identify which temperature is the best for PRF treatment. Results PRF at 42°C, 50°C and 60°C significantly alleviated the pain in CCI rats. The therapeutic effects of 50°C and 60°C were similar, and both were better than 42°C. In addition, PRF using 42°C, 50°C, and 60°C mediated nerve injury to sciatic nerve were grade 1, 1, and 2, respectively. The concentration of M-ENK in spinal cord increased accompanying with the increasing of the temperature of PRF. Conclusions PRF using 50°C could induce less damage while achieving better improvement of mechanical and thermal pain threshold than 42°C and 60°C in CCI rats, which may be achieved by promoting the expression of M-ENK in spinal cord. [ABSTRACT FROM AUTHOR]

Objective Generator site pain is a relatively common phenomenon in patients undergoing spinal cord stimulation (SCS) that complicates management and effective pain relief. This pain may be managed conservatively, with repositioning of the battery and, in some cases, with explant. Here we explore our experience with management of generator site pain ("pocket pain") in a large single-center study. Methods All SCS permanent implants and implantable pulse generator (IPG) placements over 9 years were reviewed. Of 785 cases, we identified 43 patients with pocket pain (5.5%). Demographics and treatments of the pocket pain cohort were analyzed. Results The mean age (± SEM) of the pocket pain cohort was 46.86 ± 1.06, and there were 10/33 males/females. Females were overrepresented in pocket pain cohort (76.7%) when compared with the total SCS cohort (59.0%) (X2 = 5.93, P  = 0.015). Diagnosis included failed back surgery syndrome (51.2%), complex regional pain syndrome (23.3%), and chronic neuropathic pain (25.5%). No patients improved with conservative therapy. All patients either went on to revision (n  = 23) or explant (n  = 20). Time from initial surgery to development of pocket pain was 7.5 months (range: 0.3–88) and from pocket pain to revision surgery was 4.5 months (range: 0.4–26). In addition, significantly more pocket pain patients (65.1%) had workers' compensation (WC) insurance compared with patients without pocket pain (24.9%) (X2 = 33.3, P  < 0.001). Conclusion In our institutional experience, pocket pain was inadequately managed with conservative treatments. Being female and having SCS filed under WC increased risk of pocket pain. Future work will explore the nuances in device placement based on body shape and manual activity responsibilities. [ABSTRACT FROM AUTHOR]

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]: −.59 to −.21; FE, P  < .0001) or −0.44 (95% CI: −.70 to −.19; RE, P  = .0006). A SMD of −0.21 (95% CI: −.32 to −.10; FE) or −0.26 (95% CI: −.42 to −.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. [ABSTRACT FROM AUTHOR]

Objective Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics. Methods PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g. drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis. Results A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender. Conclusions This study highlights the need for accessible guidance for non–pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics. [ABSTRACT FROM AUTHOR]

Objective Acute neuropathic pain is a significant diagnostic challenge, and it is closely related to our understanding of both acute pain and neuropathic pain. Diagnostic criteria for acute neuropathic pain should reflect our mechanistic understanding and provide a framework for research on and treatment of these complex pain conditions. Methods The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership with the U.S. Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) collaborated to develop the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) for acute pain. A working group of experts in research and clinical management of neuropathic pain was convened. Group members used literature review and expert opinion to develop diagnostic criteria for acute neuropathic pain, as well as three specific examples of acute neuropathic pain conditions, using the five dimensions of the AAAPT classification of acute pain. Results AAAPT diagnostic criteria for acute neuropathic pain are presented. Application of these criteria to three specific conditions (pain related to herpes zoster, chemotherapy, and limb amputation) illustrates the spectrum of acute neuropathic pain and highlights unique features of each condition. Conclusions The proposed AAAPT diagnostic criteria for acute neuropathic pain can be applied to various acute neuropathic pain conditions. Both the general and condition-specific criteria may guide future research, assessment, and management of acute neuropathic pain. [ABSTRACT FROM AUTHOR]

Objectives This is a prospective, blinded, case–control study of patients with chronic pain using body diagrams and colored markers to show the distribution and quality of pain and sensory symptoms (aching, burning, tingling, numbness, and sensitivity to touch) experienced in affected body parts. Methods Two pain physicians, blinded to patients' clinical diagnoses, independently reviewed and classified each colored pain drawing (CPD) for presence of neuropathic pain (NeuP) vs. non-neuropathic pain (NoP). A clinical diagnosis (gold standard) of NeuP was made in 151 of 213 (70.9%) enrolled patients. Results CPD assessment at "first glance" by both examiners resulted in correctly categorizing 137 (64.3% by examiner 1) and 156 (73.2% by examiner 2) CPDs. Next, classification of CPDs by both physicians, using predefined criteria of spatial distribution and quality of pain-sensory symptoms, improved concordance to 212 of 213 CPDs (Kappa = 0.99). The diagnostic ability to correctly identify NeuP and NoP by both examiners increased to 171 (80.2%) CPDs, with 80.1% sensitivity and 80.6% specificity (Kappa = 0.56 [95% confidence interval: 0.44–0.68]). The severity scores for pain and sensory symptoms (burning, tingling, numbness, and sensitivity to touch) on the Neuropathic Pain Questionnaire were significantly elevated in NeuP vs. NoP (P < 0.001). Conclusions This study demonstrates good performance characteristics of CPDs in identifying patients with NeuP through the use of a simple and easy-to-apply classification scheme. We suggest use of CPDs as a bedside screening tool and as a method for phenotypic profiling of patients by the quality and distribution of pain and sensory symptoms. [ABSTRACT FROM AUTHOR]

Objective Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation. Design Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2 weeks (once daily): 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1 week, 1 month, and 3 months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory. Results Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P <0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings. Conclusions Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain. [ABSTRACT FROM AUTHOR]

Objective Cranial pain is a condition that has a negative impact on human lives, and occipital neuralgia is among its causes. This study aims to evaluate the clinical characteristics and therapeutic results of a series of patients with occipital neuralgia. Design Prospective registry (observational study). Settings Headache outpatient clinic in a tertiary hospital. Subjects Sixty-eight cases. Methods Demographic and nosological characteristics have been analyzed, as well as treatment response of occipital neuralgia. All patients were recruited between January 2008 and January 2018, and the diagnosis of occipital neuralgia was made according to the International Headache Society (International Classification of Headache Disorders) criteria being utilized at the time of diagnosis. Results Sixty-eight patients were diagnosed with occipital neuralgia, which corresponded to 1.2% of the total number of patients (5,515) who visited our Headache Unit during the aforementioned period. Fifty-four (79.4%) of them were female. Baseline pain was present in 62 (91.1%) patients, and exacerbations in 42 (61.8%). Latency from onset (range) was 27.7 ± 56.1 (1–360) months. Conclusions Occipital neuralgia is an uncommon disorder in the sample explored. The prolonged latency between the onset of symptoms and diagnosis suggests that there should be an increased awareness of this disorder. [ABSTRACT FROM AUTHOR]

Background Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve. Methods Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery. Results The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature. Conclusions Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments. [ABSTRACT FROM AUTHOR]

Objective To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS). Design Prospective, open-label, single-arm pilot study. Setting University hospital. Subjects Seventeen patients with diagnosed BMS were included. Methods Subjects were treated for 4 weeks with a full cannabis plant extract, which was prepared from standardized plant material (cannabis flos) in specialized pharmacies by means of Romano-Hazekamp extraction and was diluted in oil (1 g of cannabis in 10 g of olive oil). The primary outcome was the change in pain intensity (assessed by the visual analog scale, Present Pain Intensity scale, McGill Pain Questionnaire, and Oral Health Impact Profiles) at the end of the protocol and during the succeeding 24 weeks; the neuropathic pain was also investigated with a specific interview questionnaire (DN4-interview [Douleur Neuropathique en 4 Questions]). Levels of anxiety and depression were considered as secondary outcomes, together with reported adverse events due to the specified treatment. Results Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events. Conclusions In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however. [ABSTRACT FROM AUTHOR]

Objective Our aim was to give an overview of the effectiveness of adjunctive analgesics in head and neck cancer (HNC) patients receiving (chemo-) radiotherapy. Design Systematic review. Interventions This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched for studies concerning "head neck cancer," "adjunctive analgesics," "pain," and "radiotherapy." Outcome Measures Pain outcome, adverse events, and toxicity and other reported outcomes, for example, mucositis, quality of life, depression, etc. Results Nine studies were included in our synthesis. Most studies were of low quality and had a high risk of bias on several domains of the Cochrane Collaboration tool. Only two studies comprised high-quality randomized controlled trials in which pregabalin and a doxepin rinse showed their effectiveness for the treatment of neuropathic pain and pain from oral mucositis, respectively, in HNC patients receiving (chemo-) radiotherapy. Conclusions More high-quality trials are necessary to provide clear evidence on the effectiveness of adjunctive analgesics in the treatment of HNC (chemo-) radiation-induced pain. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with chronic neuropathic pain after hemipelvectomy who received intraganglionic lidocaine injections under CT guidance, demonstrating a transient but significant reduction in pain. Topics include the challenges of managing post-amputation and phantom limb pain, the potential benefits of targeting dorsal root ganglion (DRG) neurons for pain relief, and the use of image-guided intraganglionic injection techniques for precise drug delivery to DRGs.

The article presents the discussion on Total knee arthroplasty (TKA) being one of the most common and efficacious ways managing severe knee osteoarthritis. Topics include proposed pathophysiological mechanisms for the development of neuropathic pain mainly of mechanical forces during surgery; and dorsal root ganglion stimulation (DRG-S) emerging as a potential long-term solution for chronic post-TKA pain.

Objective To evaluate the effect of multilevel single-shot thoracic paravertebral blockade (PVB) on the occurrence of chronic postsurgical pain (CPSP) in patients undergoing breast cancer surgery. Design A randomized controlled trial with two parallel groups. Setting A tertiary hospital. Methods Patients scheduled for breast cancer surgery were randomized to receive either ultrasound-guided multilevel single-shot PVB from T2 to T5 (the PVB group) or nothing (the control group). Surgery was then performed under general anesthesia. Patients were followed up for 12 months after surgery. The primary end point was incidence of CPSP at six months after surgery. Results A total of 218 patients were enrolled and randomized; of these, 208 and 204 completed six- and 12-month follow-up, respectively. The incidence of CPSP at six months was significantly lower in the PVB group (12.5% [13/104]) than in the control group (24.0% [25/104], relative risk = 0.52, 95% CI = 0.28–0.96, P  = 0.031). Pain scores within 48 hours both at rest and with movement were lower in the PVB group than the control group (P  = 0.006 and P  < 0.001, respectively). The percentages of patients with neuropathic pain were also lower in the PVB group than the control group at both six and 12 months after surgery (P  = 0.016 and 0.028, respectively). Adverse events did not differ between groups. Conclusions For patients undergoing breast cancer surgery, multilevel single-shot PVB reduces the incidence of CPSP at six months; it also improves early postoperative analgesia and reduces neuropathic pain at six and 12 months after surgery. [ABSTRACT FROM AUTHOR]

Objective Pulsed radiofrequency (PRF) is a nonablative pain treatment that uses radiofrequency current in short high-voltage bursts, resulting in interruption of nociceptive afferent pathways. We conducted a systematic review with the aim to create a synthesis of evidence about the efficacy and safety of PRF applied to the dorsal root ganglion (DRG) for the treatment of neuropathic pain. Methods We searched MEDLINE, CINAHL, Embase, and PsycINFO through January 8, 2019, as well as ClinicalTrials.gov and the clinical trial register of the World Health Organization. All study designs were eligible. We assessed risk of bias using the Cochrane tool for randomized controlled trials and the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). We assessed level of evidence using the Oxford tool and quality of evidence with GRADE. Results We included 28 studies with participants suffering from lumbosacral, cervical, or thoracic radicular pain, post-herpetic neuralgia, neuropathicbone pain in cancer patients, or carpal tunnel syndrome. Only five studies were randomized controlled trials (RCTs), while others were of nonrandomized designs, predominantly before and after comparisons. A total of 991 participants were included, with a median number (range) of 31 (1–101) participants. Only 204 participants were included in the RCTs, with a median number (range) of 38 (23–62) participants. The overall quality of evidence was low, as the majority of the included studies were rated as evidence level 4 or 5. The quality of evidence was very low. Conclusions Evidence about the efficacy and safety of PRF of the DRG for the treatment of neuropathic pain is based mainly on results from very small studies with low evidence quality. Current research results about the benefits of PRF of the DRG for the treatment of neuropathic pain should be considered preliminary and confirmed in high-quality RCTs with sufficient numbers of participants. [ABSTRACT FROM AUTHOR]

Background With its high temporal resolution, electroencephalography (EEG), a technique that records electrical activity of cortical neuronal cells, is a potentially suitable technique to investigate human somatosensory processing. By using EEG, the processing of (nociceptive) stimuli can be investigated, along with the functionality of the nociceptive pathway. Therefore, it can be applied in chronic pain patients to objectify whether changes have occurred in nociceptive processing. Typically, so-called event-related potential (ERP) recordings are used, where EEG signals are recorded in response to specific stimuli and characterized by latency and amplitude. Objective To summarize whether differences in somatosensory processing occur between chronic pain patients and healthy controls, measured with ERPs, and determine whether this response is related to the subjective pain intensity. Design Systematic review. Setting and Methods PubMed, Web of Science, and Embase were consulted, and 18 case–control studies were finally included. Subjects The chronic pain patients suffered from tension-type headache, back pain, migraine, fibromyalgia, carpal tunnel syndrome, prostatitis, or complex regional pain syndrome. Results Chronic neuropathic pain patients showed increased latencies of the N2 and P2 components, along with a decreased amplitude of the N2-P2 complex, which was also obtained in FM patients with small fiber dysfunction. The latter also showed a decreased amplitude of the N2-P3 and N1-P1 complex. For the other chronic pain patients, the latencies and the amplitudes of the ERP components did not seem to differ from healthy controls. One paper indicated that the N2-P3 peak-to-peak amplitude correlates with the subjective experience of the stimulus. Conclusions Differences in ERPs with healthy controls can mostly be found in chronic pain populations that suffer from neuropathic pain or where fiber dysfunction is present. In chronic pain populations with other etiological mechanisms, limited differences were found or agreed upon across studies. [ABSTRACT FROM AUTHOR]