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Spinal cord stimulation (SCS) is a well-established treatment for chronic neuropathic pain. However, over- or underdelivery of the SCS may occur because the spacing between the stimulating electrodes and the spinal cord is not fixed; spacing changes with motion and postural shifts may result in variable delivery of the SCS dose and, in turn, a suboptimal therapy experience for the patient. The evoked compound action potential (ECAP)-a measure of neural activation-may be used as a control signal to adapt SCS parameters in real time to compensate for this variability. In this prospective, multicenter, randomized, single-blind, crossover trial, reduction in overstimulation intensity was used as a perceptual measure to evaluate a novel ECAP-controlled, closed-loop (CL) SCS algorithm relative to traditional open-loop (OL) SCS. The primary outcome used a Likert scale to assess sensation during activities of daily living with CL versus OL SCS. Of the 42 subjects in the intent-to-treat analysis set, 97.6% had a reduction in sensation with CL versus OL SCS. The primary objective was met as the lower confidence limit (87.4%) exceeded the performance goal of 50% (P < .001). A total of 88.1% (37/42) of subjects preferred CL and 11.9% (5/42) preferred OL SCS. SCS dose consistency during CL SCS was demonstrated by the reduced variability in ECAP amplitude with CL SCS (standard deviation: 8.72 µV) relative to OL SCS (standard deviation: 19.95 µV). Together, these results demonstrate that the ECAP-controlled, CL algorithm reduces or eliminates unwanted sensation, and thereby provides a more preferred and consistent SCS experience. PERSPECTIVE: Patients with chronic pain need durable and dependable options for pain relief. SCS is an important therapy option, and new technology advancements could improve long-term therapy use. CL SCS offers a preferred and more consistent therapy experience for patients that could lead to increased therapy utilization and reliable therapy outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest None declared

Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAG CamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAG CamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAG CamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAG CamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAG CamkIIα+ neurons., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Zhu et al.)

Objective: Rehabilitation interventions for chronic pain typically include education, cognitive behavioural therapy, and exercise therapy, or a combination of these. A systematic review and meta-analysis of rehabilitation interventions for neuropathic pain was conducted., Design: Randomized controlled trials were identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and PsycINFO databases from inception up to 3 March 2022., Subjects/patients: Adults with chronic (> 3 months) neuropathic pain., Methods: Primary outcomes were pain intensity, pain-related disability, and work participation. Secondary outcomes were quality of life, emotional strain, insomnia, and adverse outcomes, according to VAPAIN guidelines. Analyses were made post-intervention, which was defined as the assessment point immediately following the intervention or at the first-time measurement conducted after the intervention period., Results: In total, 15 studies (total population, n = 764) were incorporated. Most common interventions were cognitive behavioural programmes including acceptance and commitment therapy (n = 4), mindfulness-based interventions (n = 5), and yoga (n  =  2). Psychological interventions reduced both pain intensity (SMD -0.49, 95% CI -0.88 to -0.10) and pain-related disability (SMD -0.51, 95% CI -0.98 to -0.03), whereas other interventions had an effect on pain intensity but not on pain-related disability., Conclusion: Rehabilitation interventions, and psychological interventions in particular, seem to be of value for patients with chronic neuropathic pain.

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.

Objective: Dorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients' one-week DRG stimulation trials., Materials and Methods: Patients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test., Results: In total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7-19.4], 3.40 [1.4-8.4], and 5.7 [0.8-17.6]; t90, 22.0 [10.7-71.0], 7.6 [3.6-19.8], and 20.9 [14.2-31.2], respectively). t90 times differed significantly by pain type (p = 0.040)., Conclusions: This study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted., Competing Interests: Conflict of Interest Kenneth B. Chapman reports a relationship with Abbott that includes funding grants. The remaining authors reported no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Stimulation of dorsal root ganglion (DRG) is an ideal neuromodulative intervention, providing pain relief in localized chronic pain conditions because γ-band oscillations reflect the intensity of ongoing chronic pain in patients affected., Objective: We aimed to observe the role of cortical γ-band power associated with the relief of chronic neuropathic pain through DRG stimulation (DRGS)., Materials and Methods: We examined nine patients (two women, mean age 56.8 years; range, 36-77 years) diagnosed with chronic neuropathic pain who underwent DRGS therapy. We used the numeric rating scale (NRS) on the painful limb and simultaneously recorded the electroencephalography to assess the broadband γ power. Assessments were conducted on the first day and on the seventh day after implantation of the DRGS system and then compared and correlated with the results of the NRS., Results: The NRS scores showed a significant decrease from the first day to the seventh day (p = 0.007). The resting-state γ power revealed a significant decrease (p = 0.021) between 30 and 45 Hz, recorded through the central electrode contralateral to the painful limb from the first day (mean [M] = 0.46, SD = 0.25) to the seventh day (M = 0.31, SD = 0.12) after DRGS. There was no significant change in the resting-state γ-band power recorded through the central electrode ipsilateral to the painful limb. However, we found a positive correlation in the γ-band power (r s  = 0.628, p = 0.005) with the NRS rating., Conclusions: A lateralized decrease in broadband γ power may be considered further evidence supporting a reduction in the hyperexcitability of the nociceptive system in response to DRGS therapy. In the future, γ-band power could serve as a biomarker for assessing the efficacy of DRGS during the seven-day test phase preceding the implantation of the DRGS system., Competing Interests: Conflict of Interest Matthias Hubert Morgalla has been a speaker for Abbott. The remaining authors reported no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using directional VP deep brain stimulation (DBS) in patients treated for chronic neuropathic pain., Methods: Six patients with central (four) or peripheral (two) neuropathic pain were treated by VP DBS using directional leads in a prospective study (clinicaltrials.gov NCT03399942). Lead-DBS toolbox was used for leads localization, visualization, and modeling of the volume of tissue activated (VTA). Stimulation was delivered in each direction, 1 month after surgery and correlated to the location of stimulation-induced paresthesias. The somatotopy was modeled by correlating the respective locations of paresthesias and VTAs. We recorded 48 distinct paresthesia maps corresponding to 48 VTAs (including 36 related to directional stimulation)., Results: We observed that, in each patient, respective body representations of the trunk, upper limb, lower limb, and head were closely located around the lead. These representations differed across patients, did not follow a common organization and were not concordant with the previously described somatotopic organization of the sensory thalamus., Interpretation: Thalamic reorganization has been reported in chronic pain patients compared to non-pain patients operated for movement disorders in previous studies using intraoperative recordings and micro-stimulation. Using a different methodology, namely 3D representation of the VTA by the directional postoperative stimulation through a stationary electrode, our study brings additional arguments in favor of a reorganization of the VP thalamic somatotopy in patients suffering from chronic neuropathic pain of central or peripheral origin., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

BACKGROUND Chronic kidney disease (CKD) is a growing global health concern. Chronic pain, as a common symptom of CKD, particularly among patients with end-stage renal disease (ESRD), is influenced by complications, dialysis procedures, and comorbidities. We aimed to evaluate chronic pain and probable neuropathic pain in 96 dialysis patients with ESRD using the Douleur Neuropathique 4 (DN4) questionnaire. MATERIAL AND METHODS A total of 96 patients from a single dialysis center were enrolled for the purpose of this study. ESRD was caused by diseases causing kidney damage, such as diabetes. The average duration of maintenance dialysis was 4.6±5.67 years. Comorbidities, functional and mental assessment, and pharmacological treatment data were collected using a questionnaire. The satisfaction with life scale was also used. Chronic pain was defined as lasting more than 3 months. The DN4 was used to determine the neuropathic component of pain. RESULTS Chronic pain was observed in 63.5% of the study participants, with 47.5% of them reporting the presence of neuropathic pain accompanied by a neuropathic component. Significantly more patients with chronic pain reported mood disorders and reduced life satisfaction, but there was no difference in their activities of daily living-assessed functional status or duration of dialysis. Patients experiencing chronic pain received non-steroidal anti-inflammatory drugs, paracetamol, and opioids. CONCLUSIONS Chronic pain, especially with a neuropathic component, is highly prevalent in patients with CKD, and its treatment remains ineffective. Undiagnosed components of pain can contribute to underdiagnosis and inadequate therapy. Further studies and staff education are needed to address this important issue.

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)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Purpose of Review: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain., Recent Findings: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians., (© 2024. The Author(s).)

Objectives: To provide a systematic review of the literature on the effects of peripheral magnetic stimulation (PMS) in the treatment of chronic peripheral neuropathic pain., Methods: A systematic search of MEDLINE, EMBASE, CENTRAL, CINHAL, Web of Science, and ProQuest was conducted from inception to July 2023 to identify studies of any design published in English language that enrolled adult patients (≥18 years) that received PMS for treatment of a chronic peripheral neuropathic pain disorder (pain > 3 months)., Results: Twenty-three studies were identified which included 15 randomized controlled trials (RCTs), five case series, two case reports, and one non-randomized trial. PMS regimens varied across studies and ranged from 5 to 240 min per session over 1 day to 1 year of treatment. Results across included studies were mixed, with some studies suggesting benefits while others showing no significant differences. Of nine placebo-controlled RCTs, four reported statistically significant findings in favor of PMS use. In the meta-analysis, PMS significantly reduced pain scores compared to control within 0-1 month of use (mean difference -1.64 on a 0-10 numeric rating scale, 95% confidence interval -2.73 to -0.56, p = 0.003, I 2  = 94%, 7 studies [264 participants], very low quality of evidence), but not at the 1-3 months and >3 months of PMS use (very low and low quality of evidence, respectively). Minimal to no adverse effects were reported with PMS use., Discussion: There is limited and low-quality evidence to make definitive recommendations on PMS usage, however, the available data is encouraging, especially for short-term applications of this novel modality. Large high-quality randomized controlled trials are required to establish definitive efficacy and safety effects of PMS., (© 2023 World Institute of Pain.)

Objective: This observational study investigated whether central aspects of pain are associated with self-management domains in individuals with chronic low back pain (CLBP) undertaking a pain management program., Methods: Individuals with CLBP provided pain sensitivity and self-management data at baseline (n = 97) and 3-months (n = 87). Pressure pain detection threshold (PPT) at the forearm, temporal summation (TS) and conditioned pain modulation (CPM), Widespread Pain Index (WPI), and a Central Aspects of Pain factor (CAPf) were considered as central aspects of pain. Self-management was measured using the 8 domains of the Health Education Impact Questionnaire, as well as Pain Self Efficacy and Health Care Utilisation questionnaires., Results: PPT, CPM, WPI and CAPf predicted worse performance in several self-management domains at 3-months (r = 0.21 to 0.54, p < 0.05 overall). In multivariable regression models (adjusted for baseline scores of self-management, depression, catastrophization, pain and fatigue) low PPT, high TS, and high CAPf at baseline predicted poorer self-management at 3 months (R 2 =0.14 to 0.52, β = -0.37 to 0.35, p < 0.05)., Conclusions: Central aspects of pain are associated with impaired self-management, over and above effects of pain intensity, fatigue, depression and catastrophizing., Practice Implications: Treatments that target central aspects of pain might help improve self-management in people with CLBP., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof David Walsh has received research grants from Pfizer Ltd., Eli Lilly, Orion Pharma, UCB Pharma and non-personal pecuniary consultancy fees from GlaxoSmithKline plc, AKL Research & Development Limited, Pfizer Ltd, Eli Lilly and Company, Galapagos, Contura International, and AbbVie Ltd. Dr Daniel McWilliams has received research grants from Pfizer Ltd. And Eli Lilly. Dr Paul Hendrick and Dr Vasileios Georgopoulos have no relevant interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation technique that has shown promising results in the treatment of chronic pain conditions. We present a case of a difficult lead extraction during the explantation of a DRG-S device. The lead was unable to be removed despite multiple attempts until a sheath and stylet were used to facilitate extraction. As DRG-S utilization becomes more widespread, DRG-S device explantation will inevitably become more common. The technique described in this report may be beneficial in certain cases of difficult DRG-S lead extraction., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Background: Nonsurgical refractory back pain (NSRBP) is broadly defined as chronic refractory back pain in patients who have not had previous spine surgery and, because they are deemed inappropriate candidates for surgery, are reliant on conventional medical management (CMM), which often provides poor long-term outcomes. High-frequency spinal cord stimulation (10kHz SCS) has demonstrated high rates of pain relief and improvements in functioning in patients with NSRBP. However, despite the use of temporary trial stimulation to select patients who will respond to therapy, some patients fail to achieve long-term therapy response with permanent implants. Prediction analysis founded on patients' baseline characteristics may enrich the appropriate selection of patients for permanent implantation., Objectives: To examine baseline patient characteristics to predict long-term pain and functional responses to treatment with 10 kHz SCS for NSRBP., Study Design: A retrospective analysis of baseline patient characteristics as predictors of 24-month pain and functional outcomes from a previous multicenter randomized controlled trial of 10 kHz SCS in patients with NSRBP., Patients: Patients diagnosed with chronic, neuropathic, axial, low back pain refractory to CMM who had had no previous spine surgery, were deemed unsuitable candidates for it according to a spine surgeon, were implanted with 10kHz SCS and continued with CMM for up to 24 months., Methods: The baseline characteristics of and 24-month outcomes in the 125 implanted patients who participated in the NSRBP randomized controlled trial (RCT) were included in this analysis. The baseline characteristics included demographics, baseline pain on the visual analog scale (VAS), baseline function based on the Oswestry Disability Index (ODI), mental health according to the patient health questionnaire-9 (PHQ-9), neuropathic pain as measured by PainDETECT, and each patient's temporary trial response. Patient response at 24 months was defined as absolute change from the baseline on the VAS and ODI, and each patient was also classified as a pain responder (achieving at least a 50% decrease in VAS pain score from the baseline) and a function responder (at least a 10-point decrease in ODI or a 24-month score of no more than 20 points). Multivariate prediction models based on regression and classification and regression tree (CART) techniques were developed using the response variables discussed above as the dependent variables and the baseline characteristics as the independent variables., Results: Different factors contributed to pain and functional outcomes. Patients presenting with neuropathic pain (PainDETECT >= 19) and female gender had higher odds of being pain responders to 10 kHz SCS therapy than did males and those without neuropathic pain. Both higher age and depression score (PHQ-9) independently reduced the odds that a patient would be an ODI responder. Years since diagnosis, the reason the patient was deemed unsuitable for spine surgery, and pain etiology were not predictive of pain or functional outcomes., Limitations: A retrospective sub-analysis of a single pragmatic randomized controlled trial., Conclusions: There may be an opportunity to increase pain relief and functional improvement if additional patient screening accompanies the temporary lead trial. The presence of neuropathic pain, female gender, age, and depression had some predictive value, but this analysis demonstrates the treatment efficacy of 10 kHz SCS across a wide range of patients with NSRBP.

Introduction: Spinal cord stimulation (SCS) is a modern neuromodulation technique extensively proven to be an effective modality for treatment of chronic neuropathic pain. It has been mainly studied for complex regional pain syndrome (CRPS) and failed back surgery syndrome (FBSS) and recent data almost uniformly establishes its statistically significant positive therapeutic results. It has also been compared with other available treatment modalities across various studies. However, long term data on maintenance of its efficacious potential remains less explored. Few studies have reported data on long follow-up times (>= 12 months) and have compared its efficacy with other treatment options for chronic pain, respectively. Our study pools and analyzes the available data and compares SCS with other treatment options. It also analyzes the efficacy of SCS in long term management of patients with chronic pain., Evidence Acquisition: We reviewed all the data available on MEDLINE, Embase and Cochrane CENTRAL using a search strategy designed to fit our pre-set inclusion and exclusion criteria. Both single-arm and double-arm studies were included. The primary outcome was defined as decrease of visual analogue scale (VAS) by >50% at 6, 12 and/or 24 months after SCS., Evidence Synthesis: According to the pooled data of double-arm studies, SCS has unanimously proven its superiority over other treatment options at 6 months follow-up; however it fails to prove statistically significant difference in results at longer treatment intervals. Dorsal root ganglion stimulation, a relatively recent technique with the same underlying physiologic mechanisms as SCS, showed far more promising results than SCS. Single-arm studies show around 70% patients experiencing greater than 50% reduction in their VAS scores at 6 and 12 months., Conclusions: SCS is a viable option for management of chronic neuropathic pain secondary to FBSS and CRPS. However, data available for its long term efficacy remains scarce and show no further statistically significant results.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Treatment of persistent spinal pain syndrome (PSPS) is challenging. Chronic pain associated with PSPS can lead to an impaired ability to work., Objective: To obtain information on whether receiving a disability pension (DP) affects pain and pain treatments in retiring working-age PSPS patients. Neuropathic pain medication and antidepressant use were considered as an indicator of neuropathic pain., Methods: The study group comprised 129 consecutive PSPS patients with spinal cord stimulation (SCS) devices implanted at Kuopio University Hospital Neurosurgery between January 1, 1996, and December 31, 2014. Purchase data of gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors from January 1995 to March 2016, as well as the data on working ability, were retrieved from national registries., Results: The data showed that 28 of 129 (21.7%) SCS permanent patients had a DP, and 27 had a sufficient follow-up time (two years before and one year after DP). Most patients (61%) used neuropathic pain medications during the follow-up, while 44% used antidepressants. Most patients (70%, n  = 19) retired because of dorsopathies. The dose of gabapentinoids started to increase before the DP; after the DP, the doses started to increase again after the decrease but remained at a lower level., Conclusions: Neuropathic pain medication and antidepressant use suggest that pain continues after the DP-that is, pensioners continue to experience inconvenient chronic pain. Resources for patient care are therefore needed after the DP. However, the DP reduces the dose increase of gabapentinoids; the dose is higher immediately before retirement than at the end of the follow-up., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Hanna Kaijankoski et al.)

The aims of this qualitative research were (1) to gain more insight in the diagnostic and treatment history of patients with chronic temporomandibular disorder (TMD) pain; (2) to get a deeper understanding of possible factors that are involved in the possible delay in setting a TMD-pain diagnosis and receiving appropriate treatment; and (3) to get a deeper understanding of the perspectives and experiences of chronic TMD-pain patients on the possible improvement of various aspects of their diagnostic and treatment journey.MethodsIn this narrative research, semi-structured interviews took place with patients who experienced chronic orofacial pain (OFP) for at least three years before getting diagnosed with, and treated for, TMD pain by an OFP specialist in an interprofessional setting.ResultsIn total, ten patients were interviewed in-depth. Patients experienced their chronic OFP in different ways, but all reported a significant impact of their pain on their quality of life. All patients visited numerous health care professionals before their TMD diagnosis was set. Among others, they underwent anti-neuropathic pain medication therapies and invasive surgeries, which did not significantly reduce their chronic OFP. The interprofessional TMD-pain treatment reduced the suffering of the chronic OFP substantially, also 6 months after the start of therapy, and improved the quality of life for all patients. In most of them, the OFP intensity was also decreased.ConclusionChronic TMD-pain patients with a history of neuropathic pain treatment may experience a long journey until receiving the appropriate diagnosis and treatment. This stresses the need to improve the implementation of chronic TMD-pain guidelines., (© 2023. The Author(s).)

Objectives: Motor cortex stimulation (MCS) is an effective technique in treating chronic intractable pain for some patients. However, most studies are small case series (n < 20). Heterogeneity in technique and patient selection makes it difficult to draw consistent conclusions. In this study, we present one of the largest case series of subdural MCS., Materials and Methods: Medical records of patients who underwent MCS at our institute between 2007 and 2020 were reviewed. Studies with at least 15 patients were summarized for comparison., Results: The study included 46 patients. Mean age was 56.2 ± 12.5 years (SD). Mean follow-up was 57.2 ± 41.9 months. Male-to-female ratio was 13:33. Of the 46 patients, 29 had neuropathic pain in trigeminal nerve territory/anesthesia dolorosa; nine had postsurgical/posttraumatic pain; three had phantom limb pain; two had postherpetic pain, and the rest had pain secondary to stroke, chronic regional pain syndrome, and tumor. The baseline numeric rating pain scale (NRS) was 8.2 ± 1.8 of 10, and the latest follow-up score was 3.5 ± 2.9 (mean improvement of 57.3%). Responders comprised 67% (31/46)(NRS ≥ 40% improvement). Analysis showed no correlation between percentage of improvement and age (p = 0.352) but favored male patients (75.3% vs 48.7%, p = 0.006). Seizures occurred in 47.8% of patients (22/46) at some point but were all self-limiting, with no lasting sequelae. Other complications included subdural/epidural hematoma requiring evacuation (3/46), infection (5/46), and cerebrospinal fluid leak (1/46). These complications resolved with no long-term sequelae after further interventions., Conclusion: Our study further supports the use of MCS as an effective treatment modality for several chronic intractable pain conditions and provides a benchmark to the current literature., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Ninety-Hz active-recharge spinal cord stimulation (SCS) applied at below sensory-threshold intensity, as used with fast-acting subperception therapy spinal cord stimulation, has been shown clinically to produce significant analgesia, but additional characterization is required to better understand the therapy. This preclinical study investigates the behavioral effect of multiple 90-Hz SCS variants in a rodent model of neuropathic pain, focusing on charge balance and the relationship between 90-Hz efficacy and stimulation intensity., Materials and Methods: Rats (n = 24) received a unilateral partial sciatic nerve ligation to induce neuropathic pain and were implanted with a quadripolar lead at T13. Mechanical hypersensitivity was assessed before, during, and after 60 minutes of SCS. After a prescreen with 50-Hz SCS 67% motor threshold ([MT], the positive control), rats underwent a randomized-crossover study including sham SCS and several 90-Hz SCS paradigms (at 40% MT or 60% MT, either using active or pseudopassive recharge) (experiment 1, n = 16). A second, identical experiment (experiment 2) was performed to supplement data with 90-Hz SCS at 20% and 80% MT (experiment 2, n = 8)., Results: Experiment 1: At 40% MT, 90-Hz active-recharge SCS produced a significantly larger recovery to baseline than did 90-Hz pseudopassive SCS at both tested intensities and sham SCS. Experiment 2: Only the 90-Hz SCS active recharge at 40% MT and 50-Hz SCS positive control caused mean recovery to baseline that was statistically better than that of sham SCS., Conclusions: The degree to which 90-Hz SCS reduced mechanical hypersensitivity during stimulation depended on the nature of charge balance, with 90-Hz active-recharge SCS generating better responses than did 90-Hz pseudopassive recharge SCS. In addition, our findings suggest that the amplitude of 90-Hz active-recharge SCS must be carefully configured for efficacy., Competing Interests: Conflict of Interest Tianhe C. Zhang and Rosana Esteller are employees of Boson Scientific Inc. Elbert A. Joosten is a consultant for Boston Scientific Inc. Lonne Heijmans reported no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Micronutrient and metabolic compound supplementation as a method of treating chronic pain is not well understood. Case: A 58 year-old woman presented with refractory painful neuropathy. She did not respond to conservative treatment and was seeking spinal cord stimulator implantation. She underwent a biomarker panel that revealed low intracellular levels of multiple compounds. As she supplemented her deficiencies, her symptoms fully resolved, and the implant was no longer indicated. Discussion: Micronutrient and metabolic compound testing could potentially expand non-invasive treatment options for patients with refractory chronic pain. Caution should be exercised given limited regulatory oversight in the supplement industry and actively ongoing nutritional research. Conclusion: Biomarker testing panels may be a useful adjunct in the management of refractory neuropathic pain.

Background: Chronic postsurgical pain is a considerable source of disabling neuropathic pain. Rates of knee replacement surgeries are increasing, and many patients report chronic postsurgical pain in their wake. When conventional therapies prove ineffective, neuromodulation options such as dorsal root ganglion stimulation (DRGS) may be used. However, little is known about the effect of DRGS on improvements in quantitative functional outcome parameters., Materials and Methods: In a prospective observational study at two pain centers, patients with chronic postsurgical knee pain underwent implantation with a DRGS system after an interdisciplinary multimodal pain program. Ratings of pain, mood, quality of life, and function were captured at baseline and through 12 months of treatment. Quantitative measures (range of motion, walking distance, and pain medication usage) were also recorded., Results: Visual analog scale ratings of pain decreased from 8.6 to 3.0 (p < 0.0001; N = 11), and other pain measures agreed. Quality of life on the 36-Item Short Form Health Survey questionnaire improved from 69.3 to 87.6 (p < 0.0001), whereas the improvement in depression ratings was nonsignificant. International Knee Documentation Committee questionnaire ratings of function improved from 27.7 to 51.7 (p < 0.0001), which aligned with other functional measures. On average, knee range of motion improved by 24.5°, and walking distance dramatically increased from 125 meters to 1481. Cessation of opioids, antidepressants, and/or anticonvulsants was achieved by 73% of participants., Conclusions: Both subjective-based questionnaire and quantitative examination-based variables were in broad agreement on the value of DRGS in improving functionality and chronic postsurgical pain in the knee. Although this finding is limited by the small sample size, this intervention may have utility in the many cases in which pain becomes problematic after orthopedic knee surgery., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Background: Neuromodulation has been successfully used globally to address severe refractory chronic pain for over five decades. Compared to the wide acceptance that it enjoys in United States and Europe, it is fairly underutilized in Asia, including India., Objectives: We conducted the first systematic nationwide survey to provide an overview of neuromodulation in the past 20 years to investigate the practice trends for severe refractory chronic pain and barriers for the uptake of neuromodulation therapies for pain in India., Design: A 20-point detailed questionnaire survey was sent out for online completion in August 2020 to practitioners in India involved in interventions for pain. The survey was completed by 112 practitioners (10% return rate). The response data collected were analyzed, tabulated, and presented as percentages., Results: The average duration of pain practice in India for the majority of respondents was less than a decade. About 70% of practitioners expressed that they manage severe refractory pain without neuromodulation. This survey confirms that neuromodulation is grossly underutilized for pain, comprising only 10% of total neuromodulation implants performed per annum in India. The most common indications were neuropathic pain (45%) and failed back surgery syndrome (42%). The respondents expressed the main barriers to be related to the cost (85%), lack of awareness (68%), and lack of good training (59%). More than 50% of respondents also expressed difficulty of access to neuromodulation therapies for pain and acceptance by patients., Conclusion: The younger generation of pain practitioners in India is becoming more aware and convinced about the role of neuromodulation to alleviate severe pain and suffering. An all-round approach combining improved training, awareness at various levels, more flexible options of newer technology and reimbursement approval can positively influence its use. This can be achieved with the collective efforts of physicians, insurers, industry, and focused academic activities of clinical societies., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

The management of neuropathic pain in children poses an enormous challenge for pediatricians and pain management physicians. Current treatment options include physical therapy and medication management. Peripheral nerve stimulation/neuromodulation is a novel and minimally invasive treatment that can be initiated and monitored in an outpatient setting. This new technology can be a useful tool for treating pain secondary to pediatric neuropathy and chronic refractory pain after conservative management. Our case report describes the use of a peripheral nerve stimulator in the successful management of pediatric neuropathic leg pain., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation., Objectives: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG)., Study Design: This was a single-arm, prospective, multicenter, postmarket, observational study., Setting: Patients were recruited from 15 US-based comprehensive pain centers., Methods: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a >= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured., Results: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent  of both leg pain and low back pain patients demonstrated a >= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG., Limitations:   Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible., Conclusions: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable.

Introduction: Chronic pain is a common health problem that is not efficiently managed by standard analgesic treatments. There is evidence that treatment resistance may result from maladaptive brain changes in areas that are fundamental to the perception of pain. Knee osteoarthritis is one of the most prevalent causes of chronic pain and commonly associated with negative affect. Chronic knee osteoarthritis pain is also associated with altered right anterior insula functional connectivity. We posit that reversal of these brain circuit alterations may be critical to alleviate chronic pain and associated negative affect, and that this can be achieved through non-invasive neuromodulation techniques. Despite growing interest in non-invasive neuromodulation for pain relief and proven efficacy in depression, results in chronic pain are mixed with limited high-quality evidence for clinical and mechanistic efficacy. Limitations include patient heterogeneity, imprecision of target selection, uncertain blinding and protocols that may deliver pulses at subclinical efficacy., Methods and Analysis: We hence developed an optimised treatment protocol of connectivity-guided intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex with accelerated delivery on four consecutive days (allowing 4 days within the same week as protocol variation) with five daily treatment sessions that will be piloted in a sham-controlled design in 45 participants with chronic knee pain. This pilot study protocol will assess feasibility, tolerability and explore mechanistic efficacy through serial functional/structural magnetic resonance imaging (MRI) and quantitative sensory testing., Ethics and Dissemination: This pilot trial has been approved by the Ethics Committee Cornwall and Plymouth.Results of the pilot trial will be submitted to peer-reviewed journals, presented at research conferences and may be shared with participants and PPI/E advisors., Trial Registration Number: ISRCTN15404076., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Neuropathic pain affects 7% to 10% of the population and has major effects on quality of life. It is defined as pain caused by a lesion or disease of the somatosensory nervous system and may be central or peripheral. Diagnostic testing may yield inconclusive or inconsistent results, so physicians often rely on clinical judgment based on the history and physical examination findings. Questionnaires and scoring systems can aid in diagnosis. Neuropathic pain is differentiated from other types of chronic pain by abnormal sensory symptoms, such as shooting pain, burning pain, or numbness. It is difficult to manage and can be accompanied by mood and sleep disturbances. Referral for psychotherapy may be useful for these patients. Nonpharmacotherapy options include mindfulness training, transcutaneous electrical nerve stimulation, and massage. Acupuncture also may be effective, but the data are mixed. Topical drugs (eg, lidocaine, capsaicin), gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are considered first-line drugs. Tramadol is considered a second-line drug, but may considered first-line for certain patients. For persistent pain, physicians can consider referring patients to a pain specialist for nerve blocks or other procedural interventions. Opioids may be considered for refractory pain, but their additional benefit has been shown to be modest compared with those of other treatments.

Introduction: Cervical radicular pain is pain perceived in the upper limb, caused by irritation or compression of a cervical spine nerve, the roots of the nerve, or both., Methods: The literature on the diagnosis and treatment of cervical radicular pain was retrieved and summarized., Results: The diagnosis is made by combining elements from the patient's history, physical examination, and supplementary tests. The Spurling and shoulder abduction tests are the two most common examinations used to identify cervical radicular pain. MRI without contrast, CT scanning, and in some cases plain radiography can all be appropriate imaging techniques for nontraumatic cervical radiculopathy. MRI is recommended prior to interventional treatments. Exercise with or without other treatments can be beneficial. There is scant evidence for the use of paracetamol, nonsteroidal anti-inflammatory drugs, and neuropathic pain medications such as gabapentin, pregabalin, tricyclic antidepressants, and anticonvulsants for the treatment of radicular pain. Acute and subacute cervical radicular pain may respond well to epidural corticosteroid administration, preferentially using an interlaminar approach. By contrast, for chronic cervical radicular pain, the efficacy of epidural corticosteroid administration is limited. In these patients, pulsed radiofrequency treatment adjacent to the dorsal root ganglion may be considered., Conclusions: There is currently no gold standard for the diagnosis of cervical radicular pain. There is scant evidence for the use of medication. Epidural corticosteroid injection and pulsed radiofrequency adjacent to the dorsal root ganglion may be considered. [Correction added on 12 June 2023, after first online publication: The preceding sentence was corrected.]., (© 2023 The Authors. Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Complex regional pain syndrome is a chronic debilitating pain disorder that is difficult to manage, in part due to its heterogeneous clinical presentation and lack of clearly defined pathophysiology. Patients usually require a multidisciplinary approach to treatment, which can entail pharmacotherapy, physical therapy, behavioral therapy, and interventional pain procedures, such as sympathetic nerve blocks, spinal cord stimulation, and dorsal root ganglion stimulation. However, many patients continue to experience pain refractory to these multimodal strategies. Scrambler therapy (ST) is a noninvasive method of neuromodulation that is applied through cutaneous electrodes, and can alleviate chronic neuropathic pain by stimulating C-fibers and replacing endogenous pain signals with synthetic non-nociceptive signals. Although the use of ST has been reported for several types of refractory central and peripheral neuropathic pain, there is a paucity of data regarding the use of ST for complex regional pain syndrome. We present two patients with complex regional pain syndrome of the right lower extremity, who each underwent ST and experienced significant pain relief and improvement in function and quality of life.

Purpose of Review: Peripheral nerve stimulation has seen a recent upsurge in utilization for various chronic pain conditions, specifically from a neuropathic etiology, where a single peripheral nerve can be pinpointed as a culprit for pain., Recent Findings: There is conflicting evidence about the efficacy and long-term outcomes of peripheral nerve stimulation for chronic pain, with most studies being small sized. The focus of this article is to review available evidence for the utilization of peripheral nerve stimulation for chronic pain syndromes as well as upcoming evidence in the immediate postoperative realm. The indications for the use of PNS have expanded from neuropathic pain such as occipital neuralgia and post-amputation pain, to more widespread disease processes such as chronic low back pain. Percutaneous PNS delivered over a 60-day period may provide significant carry-over effects including pain relief, potentially avoiding the need for a permanently implanted system while enabling improved function in patients with chronic pain., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic pelvic pain (CPP) is a difficult condition to treat. Due to complex pelvic innervation, dorsal column spinal cord stimulation (SCS) has not been shown to produce the same effect as dorsal root ganglion stimulation (DRGS) given emerging evidence suggesting that applying DRGS may result in favorable outcomes for individuals with CPP. The aim of this systematic review is to investigate the clinical use and effectiveness of DRGS for patients with CPP., Materials and Methods: A systematic review of clinical studies demonstrating the use of DRGS for CPP. Searches were conducted using four electronic databases (PubMed, EMBASE, CINAHL, and Web of Science) across August and September 2022., Results: A total of nine studies comprising 65 total patients with variable pelvic pain etiologies met the inclusion criteria. The majority of subjects implanted with DRGS reported >50% mean pain reduction at variable times of follow-up. Secondary outcomes reported throughout studies including quality of life (QOL) and pain medication consumption were reported to be significantly improved., Conclusions: Dorsal root ganglion stimulation for CPP continues to lack supportive evidence from well-designed, high-quality studies and recommendations from consensus committee experts. However, we present consistent evidence from level IV studies showing success with the use of DRGS for CPP in reducing pain symptoms along with reports of improved QOL through periods as short as 2 months to as long as 3 years. Because the available studies at this time are of low quality with a high risk of bias, we strongly recommend the facilitation of high-quality studies with larger sample sizes in order to better ascertain the utility of DRGS for this specific patient population. At the same time, from a clinical perspective, it may be reasonable and appropriate to evaluate patients for DRGS candidacy on a case-by-case basis, especially those patients who report CPP symptoms that are refractory to noninterventional measures and who may not be ideal candidates for other forms of neuromodulation., (© 2023 World Institute of Pain.)

Small molecules directly targeting the voltage-gated sodium channel (VGSC) Na V 1.7 have not been clinically successful. We reported that preventing the addition of a small ubiquitin-like modifier onto the Na V 1.7-interacting cytosolic collapsin response mediator protein 2 (CRMP2) blocked Na V 1.7 function and was antinociceptive in rodent models of neuropathic pain. Here, we discovered a CRMP2 regulatory sequence (CRS) unique to Na V 1.7 that is essential for this regulatory coupling. CRMP2 preferentially bound to the Na V 1.7 CRS over other Na V isoforms. Substitution of the Na V 1.7 CRS with the homologous domains from the other eight VGSC isoforms decreased Na V 1.7 currents. A cell-penetrant decoy peptide corresponding to the Na V 1.7-CRS reduced Na V 1.7 currents and trafficking, decreased presynaptic Na V 1.7 expression, reduced spinal CGRP release, and reversed nerve injury-induced mechanical allodynia. Importantly, the Na V 1.7-CRS peptide did not produce motor impairment, nor did it alter physiological pain sensation, which is essential for survival. As a proof-of-concept for a Na V 1.7 -targeted gene therapy, we packaged a plasmid encoding the Na V 1.7-CRS in an AAV virus. Treatment with this virus reduced Na V 1.7 function in both rodent and rhesus macaque sensory neurons. This gene therapy reversed and prevented mechanical allodynia in a model of nerve injury and reversed mechanical and cold allodynia in a model of chemotherapy-induced peripheral neuropathy. These findings support the conclusion that the CRS domain is a targetable region for the treatment of chronic neuropathic pain.

This study compared the self-assessed health-related quality of life (HRQoL) and degree of depression between patients with chronic neuropathic nonodontogenic orofacial pain (NOFP) and healthy controls using the Short Form Survey (SF-36) health status questionnaire and Beck Depression Inventory II (BDI-II). This controlled cross-sectional study included 100 patients and 119 healthy controls. The diagnostic protocol recorded the following: 1) pain intensity using a visual analog scale for the time of examination and during the one-month prior; 2) evidence for neuropathic pain using the Leeds questionnaire for neuropathic signs and symptoms (LANSS); 3) emotional status using the BDI-II; and 4) HRQoL using the SF-36 questionnaire. The mean LANSS score was 17.18 in the patient group and 0.0 in the control group. The mean BDI-II score was 18.31 in the patient group and 5.87 in the control group. The SF-36 scores were shown with Mann-Whitney U testing to have statistically significant differences between the patient and healthy control groups in all categories. Vitality was the only SF-36 category in which the patient group scored higher than the control group. In conclusion, NOFP significantly reduces the self-reported HRQoL. NOFP is also related to the development of depression, but does not affect its severity. There is a significant correlation between depression and low quality of life in patients with NOFP., (Sestre Milosrdnice University Hospital.)

Background: Complex regional pain syndrome (CRPS) is a chronic neuropathic painful condition, sometimes associated with spinal myoclonus. For intractable cases spinal cord stimulation is an important modality of treatment but the response of specifically myoclonus to this treatment is not well described., Case Description: A 40-year old male, had a history of trauma 12 years back since when he had intractable neuropathic pain in his both upper limbs with superimposed severely disabling myoclonic jerks. He had been through multiple treatment failures. We inserted a cervical spinal cord stimulator which led to immediate cessation of myoclonic jerks, with significant improvement in visual analogue score and Oswestry disability index., Conclusion: In patients of chronic intractable cervico-brachial pain disorder with superimposed myoclonus, cervical spinal cord stimulation may be effective against the myoclonus as well as the pain.

Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. The success of SCS is dependent on candidate selection, response to trialing, and programming optimization. Owing to the subjective nature of these variables, machine learning (ML) offers a powerful tool to augment these processes. Here we explore what work has been done using data analytics and applications of ML in SCS. In addition, we discuss aspects of SCS which have narrowly been influenced by ML and propose the need for further exploration. ML has demonstrated a potential to complement SCS to an extent ranging from assistance with candidate selection to replacing invasive and costly aspects of the surgery. The clinical application of ML in SCS shows promise for improving patient outcomes, reducing costs of treatment, limiting invasiveness, and resulting in a better quality of life for the patient., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

A robust cell-free platform technology, ribosome display in combination with cloning, expression, and purification was utilized to develop single chain Fragment variable (scFv) antibody variants as pain therapy directed at the mouse cholecystokinin B (CCK-B) receptor. Three effective CCK-B peptide-specific scFvs were generated through ribosomal display technology. Soluble expression and ELISA analysis showed that one antibody, scFv77-2 had the highest binding and could be purified from bacterial cells in large quantities. Octet measurements further revealed that the CCK-B scFv77-2 antibody had binding kinetics of K D = 1.794 × 10 -8 M. Molecular modeling and docking analyses suggested that the scFv77-2 antibody shaped a proper cavity to embed the whole CCK-B peptide molecule and that a steady-state complex was formed relying on intermolecular forces, including hydrogen bonding, electrostatic force, and hydrophobic interactions. Thus, the scFv antibody can be applied for mechanistic intermolecular interactions and functional in vivo studies of CCK-BR. The high affinity scFv77-2 antibody showed good efficacy with binding to CCK-BR tested in a chronic pain model. In vivo studies validated the efficacy of the CCK-B receptor (CCK-BR) scFv77-2 antibody as a potential therapy for chronic trigeminal nerve injury-induced pain. Mice were given a single dose of the CCK-B receptor (CCK-BR) scFv antibody 3 weeks after induction of a chronic trigeminal neuropathic pain model, during the transition from acute to chronic pain. The long-term effectiveness for the reduction of mechanical hypersensitivity was evident, persisting for months. The anxiety- and depression-related behaviors typically accompanying persisting hypersensitivity subsequently never developed in the mice given CCK-BR scFv. The effectiveness of the antibody is the basis for further development of the lead CCK-BR scFv as a promising non-opioid therapeutic for chronic pain and the long-term reduction of chronic pain- and anxiety-related behaviors., Competing Interests: A.K. and K.N.W. are consultants at NeuroChronix. K.N.W. is also consultant at U.S.A. Elixeria Biopharma, Inc. No financial support was provided. The other authors declare no conflicts of interest.

Objective: Chronic pain is processed by at least three well-known pathways, two pain provoking pathways including a medial 'suffering' and lateral 'painfulness' pathway. A third descending pain pathway modulates pain but is predominantly inhibitory. Chronic pain can be seen as an imbalance between the two pain-provoking and the pain inhibitory pathways. If this assumption is correct, then the imbalance between pain input and pain suppression should reverse and normalize in response to successful, i.e., pain reducing burstDR spinal cord stimulation, one of the current treatment options for neuropathic pain., Materials and Methods: Fifteen patients, who received spinal cord stimulation for failed back surgery were included in this study, using source localized electrical brain activity and connectivity recording via EEG to identify the purported imbalance., Results: BurstDR spinal cord stimulation induces a significant change in EEG activity in both the left and right somatosensory cortex (SSC) for both θ and γ oscillations. In the dorsal anterior cingulate cortex (dACC), we observed a significant drop in both α and β oscillations. This reduction is accompanied by a change in pain intensity and suffering. BurstDR spinal cord stimulation is also associated with a reduction in θ at the pregenual anterior cingulate cortex (pgACC). Analyzing effective connectivity indicates that for the θ band, more information is sent from the pgACC to the left and right SSC. For α, increased information is sent from the pgACC to the dACC and both the left and right SSC. This is associated with a reduced θ-γ coupling in the SSC and reduced α-β coupling in dACC., Conclusion: This study suggests that chronic pain is indeed an imbalance between the ascending and descending pathways in the brain and that burst spinal cord stimulation can normalize this imbalance in the brain., Competing Interests: Declaration of competing interest Dirk De Ridder has a patent for burst stimulation. Sven Vanneste has no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Interventional pain management (IPM) options for refractory neuropathic pain (NP) have recently increased with availability of peripheral nerve stimulation (PNS) equipment and expertise. Given a lack of high-quality evidence and guidelines on this topic, we sought to understand the perception of physicians with expertise in treating NP regarding IPM and the role of PNS. We emailed a survey in March 2022 to international NP experts including pain medicine physicians, researchers, and leaders of 11 professional pain societies. No representatives from vendors of PNS systems were included in the design of the survey nor as respondents. Among 24 respondents (67% of those contacted), the distal common peroneal, tibial, and sural nerves were most frequently targeted (60%) with PNS. Persistent postsurgical pain of more than 3 months was the most common indication for PNS (84%). The aggregate NP treatment algorithm in order of median rank was non-opioid medications as first line, IPM including epidural/perineural steroid injections tied with transcutaneous electrical nerve stimulation as second line, pulsed radiofrequency (RF) tied with RF ablation/denervation as third line, temporary then permanent PNS as fourth line, followed by spinal cord stimulation, opioids, cryoablation, botulinum, peripheral nerve field stimulation, intrathecal targeted drug delivery, and others. Before offering PNS, 12 respondents (50%) indicated their preference for trialing non-neuromodulation treatments for 1-3 months. Twenty-two respondents (92%) agreed PNS should be offered early in the treatment of neuropathic pain. The most common barriers to PNS use were cost, lack of high-quality evidence in support of its use, lack of exposure to PNS in training programs, and lack of familiarity with the use of ultrasound guidance. PNS appears to have an increasing role in the treatment of NP but more research is needed on the outcomes of PNS to elucidate its role., Competing Interests: Competing interests: AH-YL is a consultant for SPR Therapeutics. AB is engaged in an Industry (Medtronic)-funded study on long-term outcomes of neuromodulation for pain. AG is a consultant for Medtronic, Nalu Medical, Rivanna Medical (NIH supported), Somme Therapeutics, Maxwell Therapeutics, and Averitas Medical, and is on the advisory board for AIS Healthcare, Hinge Health, and Tersera Medical. EO is a consultant for Medtronic, Abbott, SPR Therapeutics, Nalu, BioVentus, Invicta – equity, and Coloplast., (© American Society of Regional Anesthesia & Pain Medicine 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Perioperative nerve injuries are common and may be prevented. The estimated incidence of perioperative nerve injury is 10% to 50%. However, most of these injuries are minor and self-recovering. Severe injuries account for up to 10%. Potential mechanisms of injury are nerve stretch, compression, hypoperfusion, direct nerve trauma, or injury during vessel cannulation. Nerve injury pain usually presents as neuropathic pain ranging from mild to severe mononeuropathy and extends to the disabling complex regional pain syndrome. This review provides a clinical approach to subacute and chronic pain secondary to perioperative nerve injury, presentation, and management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Pharmacological treatments for neuropathic pain often fail despite following guidelines. Interdisciplinary Pain Rehabilitation Programs (IPRP) are an effective intervention for chronic pain conditions. Little research has investigated whether IPRP can benefit patients with chronic neuropathic pain compared to other chronic pain conditions. This study assesses the real-world effects of IPRP on patients with chronic neuropathic pain compared to non-neuropathic patients using Patient-Reported Outcome Measures (PROMs) available in the Swedish Quality Registry for Pain Rehabilitation (SQRP)., Methods: A neuropathic group of patients (n = 1,654) were identified in two steps. This group was compared to a non-neuropathic group (n = 14,355) composed of common diagnoses (low back pain, fibromyalgia, whiplash associated disorders, and Ehlers-Danlos Syndrome) in relation to background variables, three overall outcome variables, and mandatory outcome variables (pain intensity, psychological distress symptoms, activity/participation aspects and health-related quality of life variables). Of these patients 43-44% participated in IPRP., Results: At assessment, the neuropathic group reported significantly (with small effect sizes (ES)) more physician visits the previous year, older age, shorter pain durations, and less spatial extent of the pain (moderate ES). Moreover, for the 22 mandatory outcome variables, we found only clinically insignificant differences according to ESs between the groups. For patients participating in IPRP, the neuropathic group displayed equal or in some cases slightly superior results compared to the non-neuropathic group., Discussion and Conclusion: After assessing the real-world effects of IPRP, this large study found that neuropathic pain patients can benefit from the IPRP intervention. Both registry studies and RCTs are needed to better understand which patients with neuropathic pain are most suitable for IPRP and to what extent special considerations need to be made for these patients within the framework of IPRP., (© 2023. The Author(s).)

Brachial plexus avulsion injuries result in permanent motor and sensory deficits, leading to debilitating symptoms. We report the case of a 25-year-old man with chronic pain following right-sided C5-T1 nerve root avulsion without evidence of peripheral nerve injury. His pain was recalcitrant to medical and neurosurgical interventions. However, he experienced substantial (>70%) pain relief with peripheral nerve stimulation targeting the median nerve. These results agree with data suggesting collateral sprouting of sensory nerves occurs following a brachial plexus injury. Further study is needed if we are to understand the mechanisms of the peripheral nerve stimulator as a treatment option., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Purpose of Review: Patients diagnosed with neuropathic pain experience continuous or intermittent spontaneous pain throughout their lives. Pharmacological treatments often provide limited relief; therefore, a multidisciplinary approach should be utilized to manage neuropathic pain. This review examines the current literature on integrative health modalities (anti-inflammatory diets, functional movement, acupuncture, meditation, and transcutaneous therapy) for treating patients with neuropathic pain., Recent Findings: The use of an anti-inflammatory diet, functional movement, acupuncture, meditation, and transcutaneous therapy in treating neuropathic pain has been investigated in prior literature with positive outcomes. However, there remains a large void in evidence-based knowledge and clinical applicability for these interventions. Overall, integrative health offers a cost-efficient and harmless way of creating a multidisciplinary approach to managing neuropathic pain. There are many complementary approaches to treating neuropathic pain as part of an integrative medicine approach. Research is needed to explore other herbs and spices not yet reported in the peer-review literature. Additionally, follow-on research is needed to understand the clinical applicability of the proposed interventions as well as the dose and timing of the interventions to predict response and duration., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To give an overview of central aspects of pain medicine-specific clinical reasoning when assessing a pain patient. Clinical reasoning is the thinking and decision-making processes associated with clinical practice., Methods: Three core pain assessment areas that are crucial for clinical reasoning in the field of pain medicine are discussed, each of them consisting of three points., Results: First, it is important to distinguish acute, chronic non-cancer, and cancer-related pain conditions. This classical and very simple trichotomy still has important implications treatment-wise, e.g., concerning the use of opioids. Second, the pain mechanism needs to be assessed. Is the pain nociceptive, neuropathic, or nociplastic? Simply put, nociceptive pain has to do with injury of non-neural tissue, neuropathic pain is caused by a disease or lesion of the somatosensory nervous system, and nociplastic pain is believed to be related to a sensitized nervous system (c.f. the concept of "central sensitization"). This also has implications concerning treatment. Some chronic pain conditions are nowadays viewed more as diseases rather than the pain being merely a symptom. In the new ICD-11 pain classification, this is conceptualized by the characterization of some chronic pains as "primary". Third, in addition to a conventional biomedical evaluation, psychosocial and behavioral aspects must also be assessed, the pain patient being viewed as an active agent and not merely as the passive recipient of an intervention. Hence, the importance of a dynamic bio-psycho-social perspective. The dynamic interplay of biological, psychological, and social aspects must be taken into account, putative behavioral "vicious circles" thereby being identified. Some core psycho-social concepts in pain medicine are mentioned., Conclusions: The clinical applicability and clinical reasoning power of the 3 × 3 framework is illustrated by three short (albeit fictional) case descriptions., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Only three classes of pain medications have made it into clinical use in the past 60 years despite intensive efforts and the need for nonaddictive pain treatments. One reason for the failure involves the use of animal models that lack mechanistic similarity to human pain conditions, with endpoint measurements that may not reflect the human pain experience. In this issue of the JCI, Ding, Fischer, and co-authors developed the foramen lacerum impingement of trigeminal nerve root (FLIT) model of human trigeminal neuralgia that has improved face, construct, and predictive validities over those of current models. They used the FLIT model to investigate the role that abnormal, hypersynchronous cortical activity contributed to a neuropathic pain state. Unrestrained, synchronous glutamatergic activity in the primary somatosensory cortex upper lip and jaw (S1ULp-S1J) region of the somatosensory cortex drove pain phenotypes. The model establishes a powerful tool to continue investigating the interaction between the peripheral and central nervous systems that leads to chronic pain.