Clinical insights into traumatic injury of the inferior alveolar and lingual nerves: a comprehensive approach from diagnosis to therapeutic interventions.

OBJECTIVES: This scoping review explores the risk and management of traumatic injuries to the inferior alveolar and lingual nerves during mandibular dental procedures. Emphasizing the significance of diagnostic tools, the review amalgamates existing knowledge to offer a comprehensive overview. MATERIALS AND METHODS: A literature search across PubMed, Embase, and Cochrane Library informed the analysis. RESULTS: Traumatic injuries often lead to hypo-/anesthesia and neuropathic pain, impacting individuals psychologically and socially. Diagnosis involves thorough anamnesis, clinical-neurological evaluations, and radiographic imaging. Severity varies, allowing for conservative or surgical interventions. Immediate action is recommended for reversible causes, while surgical therapies like decompression, readaptation, or reconstruction yield favorable outcomes. Conservative management, utilizing topical anesthesia, capsaicin, and systemic medications (tricyclic antidepressants, antipsychotics, and serotonin-norepinephrine-reuptake-inhibitors), proves effective for neuropathic pain. CONCLUSIONS: Traumatic nerve injuries, though common in dental surgery, often go unrecorded. Despite lacking a definitive diagnostic gold standard, a meticulous examination of the injury and subsequent impairments is crucial. CLINICAL RELEVANCE: Tailoring treatment to each case's characteristics is essential, recognizing the absence of a universal solution. This approach aims to optimize outcomes, restore functionality, and improve the quality of life for affected individuals.

Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

Characteristics of Pain Changes in Rats with Nerve Injury within 24 Hours after One-Time Tuina Intervention.

Tuina, as an external treatment method of traditional Chinese medicine, has been proven to have an analgesic effect on peripheral neuropathic pain (pNP) in clinical and basic research. However, the optimal time point for the analgesic effect of tuina may vary according to different injury sensations, affecting the exploration of the initiation mechanism of tuina analgesia. The research used minor chronic constriction injury (minor CCI) model rats to simulate pNP and used the intelligent tuina manipulation simulator to simulate the three methods (point-pressing, plucking, and kneading) and three acupoints (Yinmen BL37, Chengshan BL57, and Yanglingquan GB34) for performing tuina therapy. The study evaluated the changes in pain within 24 h and the optimal time point for the efficacy of tuina analgesia in rats with minor CCI models by testing cold sensitivity threshold (CST), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). Furthermore, the study evaluated IL-10 and TNF-α expression changes through Elisa detection. The results show that tuina has both immediate and sustained analgesic effects. For the three different injury sensitivity thresholds of CST, MWT, TWL, and two cytokines of IL-10 and TNF-α, the analgesic efficacy of tuina within 24 h after intervention is significantly different at different time points.

Electroacupuncture alleviates streptozotocin-induced diabetic neuropathic pain via suppressing phosphorylated CaMKIIα in rats.

Diabetic neuropathic pain (DNP) is a frequent complication of diabetes. Calcium/calmodulin-dependent protein kinase II α (CaMKIIα), a multi-functional serine/threonine kinase subunit, is mainly located in the surface layer of the spinal cord dorsal horn (SCDH) and the primary sensory neurons in dorsal root ganglion (DRG). Numerous studies have indicated electroacupuncture (EA) takes effect in various kinds of pain. In this research, we explored whether CaMKIIα on rats' SCDH and DRG participated in DNP and further explored the mechanisms underlying the analgesic effects of EA. The DNP model in rats was successfully established by intraperitoneal injection of streptozotocin. Certain DNP rats were treated with intrathecal injections of KN93, a CaMKII antagonist, and some of the DNP rats received EA intervention. The general conditions, behaviors, the expressions of CaMKIIα and phosphorylated CaMKIIα (p-CaMKIIα) were evaluated. DNP rats' paw withdrawal threshold was reduced and the expressions of p-CaMKIIα in SCDH and DRG were upregulated compared with the Normal group, while the level of CaMKIIα showed no significance. KN93 attenuated DNP rats' hyperalgesia and reduced the expressions of p-CaMKIIα. We also found EA attenuated the hyperalgesia of DNP rats and reduced the expressions of p-CaMKIIα. The above findings suggest that p-CaMKIIα in SCDH and DRG is involved in DNP. The analgesic effect of EA in DNP might be related to the downregulation of p-CaMKIIα expression level. Our study further supports that EA can be an effective clinical treatment for DNP.

Somatotopic organization of the ventral nuclear group of the dorsal thalamus: deep brain stimulation for neuropathic pain reveals new insights into the facial homunculus.

Deep Brain Stimulation (DBS) is an experimental treatment for medication-refractory neuropathic pain. The ventral posteromedial (VPM) and ventral posterolateral (VPL) nuclei of the thalamus are popular targets for the treatment of facial and limb pain, respectively. While intraoperative testing is used to adjust targeting of patient-specific pain locations, a better understanding of thalamic somatotopy may improve targeting of specific body regions including the individual trigeminal territories, face, arm, and leg. To elucidate the somatotopic organization of the ventral nuclear group of the dorsal thalamus using in vivo macrostimulation data from patients undergoing DBS for refractory neuropathic pain. In vivo macrostimulation data was retrospectively collected for 14 patients who underwent DBS implantation for neuropathic pain syndromes at our institution. 56 contacts from 14 electrodes reconstructed with LeadDBS were assigned to macrostimulation-related body regions: tongue, face, arm, or leg. 33 contacts from 9 electrodes were similarly assigned to one of three trigeminal territories: V1, V2, or V3. MNI coordinates in the x, y, and z axes were compared by using MANOVA. Across the horizontal plane of the ventral nuclear group of the dorsal thalamus, the tongue was represented significantly medially, followed by the face, arm, and leg most laterally (p < 0.001). The trigeminal territories displayed significant mediolateral distribution, proceeding from V1 and V2 most medial to V3 most lateral (p < 0.001). Along the y-axis, V2 was also significantly anterior to V3 (p = 0.014). While our results showed that the ventral nuclear group of the dorsal thalamus displayed mediolateral somatotopy of the tongue, face, arm, and leg mirroring the cortical homunculus, the mediolateral distribution of trigeminal territories did not mirror the established cortical homunculus. This finding suggests that the facial homunculus may be inverted in the ventral nuclear group of the dorsal thalamus.

Diagnostic and therapeutic value of intracellular biomarker testing in chronic pain.

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.

Implantable Subdural Cortical Stimulation for Chronic Intractable Pain Treatment-The Mayo Experience and Review of Literature.

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.

Non-pharmacological management of neuropathic pain in older adults: a systematic review.

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.

Neuromodulation for the management of chronic pelvic pain syndromes: A systematic review.

BACKGROUND: Chronic pelvic pain is a burdensome condition that involves multiple medical sub-specialties and is often difficult to treat. Sacral stimulation for functional bladder disease has been well established, but little large-scale evidence exists regarding utilization of other neuromodulation techniques to treat chronic pelvic pain. Emerging evidence does suggest that neuromodulation is a promising treatment, and we aim to characterize the use and efficacy of such techniques for treating chronic pelvic pain syndromes. MATERIALS AND METHODS: A systematic review of the literature demonstrating the treatment of chronic pelvic pain syndromes with neuromodulation. Abstracts were reviewed and selected for inclusion, including case series, prospective studies, and randomized controlled trials (RCTs). Case studies and publications in abstract only were not included. The reporting for this systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed using MEDLINE, Embase, Cochrane Library, PubMed, CINAHL, and Scopus. RESULTS: A total of 50 studies were included in this review, three of which were randomized controlled trials, and the remaining were prospective and retrospective case series. The range of pelvic pain conditions treated included interstitial cystitis, peripheral neuralgia, pudendal neuralgia, gastrointestinal pain, urogenital pain, sacroiliac joint pain, and visceral chronic pelvic pain. We reported on outcomes involving pain, functionality, psychosocial improvement, and medication reduction. CONCLUSIONS: Neuromodulation is a growing treatment for various chronic pain syndromes. Peripheral nerve stimulation was the least studied form of stimulation. Posterior tibial nerve stimulation appears to offer short-term benefit, but long-term results are challenging. Sacral nerve stimulation is established for use in functional bladder syndromes and appears to offer pain improvement in these patients as well. Dorsal root ganglion stimulation and spinal cord stimulation have been used for a variety of conditions with promising results. Further studies of homogeneous patient populations are necessary before strong recommendations can be made at this time, although pooled analysis may also be impactful.

Percutaneous electrical nerve stimulation in post-mastectomy neuropathic pain: A case report.

Post-mastectomy pain syndrome (PMPS) is a type of chronic postsurgical pain that can be severe, debilitating and frequently encountered in clinical practice. Multiple studies have focused on prevention, identifying risk factors and treating this condition. Nonetheless, PMPS remains a complex condition to treat effectively. In this case report, we describe the use of percutaneous electrical nerve stimulation in a breast cancer patient who experienced PMPS refractory to conventional treatments.

Case report: Dorsal root ganglion stimulator lead fracture.

BACKGROUND: One of the unique advances in neuromodulation for chronic pain has been spinal cord stimulators (SCS) and dorsal root ganglion stimulators (DRG-S). These devices have aided in conditions such as neuropathic pain, complex regional pain syndromes, failed back surgery, and peripheral neuropathies. With these benefits, however, complications from implantable stimulators have included lead fractures and migration. The authors reviewed a lead migration, kinking, and subsequent fracture event involving a patient with complex regional pain syndrome (CRPS) II, who was treated with a DRG-S. CASE PRESENTATION: The case report follows this patient, from their past medical history to assessment of appropriate qualifications for neuromodulation, to successful surgical placement, to follow-up care. The authors further monitored assessment of inefficacy of pain relief, and identification of lead migration and kinking through imaging. In the process of removal, due to lead stress, lead fracturing occurred. After lead removal, the leads were fully replaced, and the patient was followed up and experienced improved pain relief. CONCLUSION: The case report assesses probable mechanisms of lead fracture and considerations for physicians for future assessment and triage of neuromodulation efficacy.

Peripheral Nervous System Pain Modulation.

The percutaneous technique of electrode insertion in the vicinity of the greater occipital nerves to treat occipital neuralgia was first described in the 1990s by Weiner and Reed. This subsequently stimulated awareness of peripheral nerve stimulation (PNS). The more recent advent emergence of a minimally invasive percutaneous approach by way of using ultrasound has further increased the interest in PNS as a viable alternative to more invasive techniques. PNS has become more popular recently and is increasingly used to treat various pain conditions. Its foundation is fundamentally based on the gate control theory, although the precise mechanism underlying its analgesic effect is still indefinite. Studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and the involvement of the cortical and subcortical areas. Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the modulation of PNS mechanisms can help guide stimulation approaches and parameters to optimize the use of PNS. his chapter aims to review the background and mechanisms of PNS modulation. PNS is becoming one of the most diverse therapies in neuromodulation due to rapid evolution and expansion. It is an attractive option for clinicians due to the simplicity and versatility of procedures that can be combined with other neuromodulation treatments or used alone. It has a distinct role in the modulation of functional conditions.

Effect of electroacupuncture on brachial plexus post-traumatic neuralgia: A case report.

Background: Brachial plexus injury is a serious peripheral nerve injury that severely disables upper limbs and affects patients' daily life and work Acupuncture and Electroacupuncture have traditionally been used to treat neuropathic pain. However, there is still lacking evidence as regard to their effects on pain following traumatic nerve and plexus lesions. Neurotmesis after brachial plexus injury also causes movement disorders of the denervated muscles and loss of sensory function in the skin. Case report: We report a case of a brachial plexus injury due to humeral fracture, predominantly involving the lower trunk and the medial cord, treated with electroacupuncture. Results. We documented a positive significant response, based on clinical examination, pain scores and neurophysiologic findings. Conclusions: Repeated Electroacupuncture can relieve neuropathic pain due to brachial plexus injury. However, additional studies are needed to verify the efficacy and effectiveness of this approach.

Peripheral Nerve Stimulation for the Management of Pediatric Neuropathic Pain.

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.

Effects of acupuncture therapy in diabetic neuropathic pain: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of acupuncture in relieving diabetic neuropathic pain and to establish a more reliable and efficient foundation for acupuncture practice in diabetes care. METHODS: The Chinese National Knowledge Infrastructure, Wanfang database, Chongqing Weipu, Chinese Biomedical Literature Database, PubMed, Embase, and Cochrane Library were all searched for a randomized controlled trial research of acupuncture for DNP. Two researchers independently performed literature screening, quality evaluation, and data extraction. After selecting studies and extracting data, we conducted the data analysis using RevMan 5.4 and Stata 14.0. The quality was assessed using the Cochrane Risk of Bias Assessment Tool. RESULTS: An extensive review of 19 studies involving 1276 patients up to April 29, 2023, found that acupuncture was successful in improving pain intensity [MD= -1.09; 95% CI (-1.28, -0.89), P < 0.00001], clinical efficacy indicating pain changes [RR= 1.22; 95% CI (1.15, 1.29), P < 0.00001], and clinical neuropathy [MD= -1.55; 95% CI ( -3.00, -0.09), P = 0.04] in DNP patients. Quality of life was also improved, with few side effects reported. CONCLUSION: According to this meta-analysis, acupuncture therapy significantly improved the clinical efficacy of pain intensity, pain changes, and clinical neuropathy in patients with DNP, improved the quality of life of patients to a certain extent, and had lower side effects. This discovery provides evidence-based and practical recommendations for the treatment of DNP patients.

Electroacupuncture alleviates neuropathic pain caused by SNL by promoting M2 microglia polarization through PD-L1.

As a common clinical disease, neuropathic pain is difficult to be cured with drugs. The occurrence and progression of pain is closely related to the response of spinal microglia. Aspartof the regulation of microglialactivity,PD-L1 playsacriticalrole. Loss of PD-L1 promoted the polarization of M1-like microglia. Increased expression of PD-L1 promoted M2-like polarization. Electroacupuncture has a significant analgesic effect in clinical practice, but its specific mechanism remains to be further explored. In this study, we verified the role of PD-L1 in EA analgesia and the underlying molecular mechanism through spinal nerve ligation (SNL) in rats and lipopolysaccharide (LPS)-treated BV2 microglial cells. Forbehavioralstudiesofrats,mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured, and spinal cord neuros were examined under transmission electron microscopyto determine changes to their myelin structure. The expression levels of PD-L1 and M1/M2-specific markers in rat spinal cord and BV2 microglial cells were measured by enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence staining and Western blot analysis. Our study showed that EA increased the pain threshold, reduced the destruction of myelin structure, promoted the expression of PD-L1 and PD-1, inhibited the MAPK signaling pathway, and promoted the conversion of microglial polarization from the M1 phenotype to the M2 phenotype in SNL rats. PD-L1 knockdown reversed these effects of EA. In addition, PD-L1 knockdown activated the MAPK signaling pathway, promoted microglial polarization to the M1 phenotype, decreased the expression of anti-inflammatory mediators and increased the expression of proinflammatory factors in LPS-stimulated BV2 microglial cells. Our results showed that EA may regulate the excitability of primary afferent neurons through PD-L1 and then inhibit the MAPK signaling pathway to promote the transformation of activated M1 microglia into M2 microglia, reduce inflammatory reactions, and finally achieve analgesic effects. A therapy targeting PD-L1 may be an effective strategy for treating neuropathic pain.

Effects of joint mobilization combined with acupuncture on pain, physical function, and depression in stroke patients with chronic neuropathic pain: A randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of joint mobilization (JM) combined with acupuncture (AC) for the treatment of pain, physical function and depression in poststroke patients. METHODS: A total of 69 poststroke patients were randomly assigned to the JM+AC group (n = 23), the JM group (n = 23), and the control group (n = 23). Patients in the JM+AC group and the JM group received JM for 30 minutes, twice a week for 12 weeks, and the JM+AC group received AC for 30 minutes separately once a week. The control group did not receive JM or AC. Pain (visual analog scale, shoulder pain and disability index, Western Ontario and McMaster universities osteoarthritis index), physical function (range of motion, 10-m walking speed test, functional gait assessment, manual function test, activities of daily living scale, instrumental activities of daily living scale), and depression (center for epidemiologic studies depression scale, Beck depression inventory) were assessed for each patient before and after the 12 weeks of intervention. RESULTS: Pain and physical function were improved significantly in the JM+AC group compared with the JM and control groups. Physical function and depression were improved significantly in the JM+AC and JM groups compared with the control group. CONCLUSION: The treatment of JM combined with AC improved pain, depression, and physical function of poststroke patients with chronic neuropathic pain in this study. This valuable finding provides empirical evidence for the designing therapeutic interventions and identifying potential therapeutic targets.

Electroacupuncture alleviates mechanical allodynia and anxiety-like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex-dorsal raphe nucleus neural circuit.

AIMS: Epidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety-like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on mechanical allodynia and anxiety-like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu ) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety-like behaviors in SNI mice. RESULTS: Electroacupuncture significantly alleviated both mechanical allodynia and anxiety-like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu -DRN projections attenuated both mechanical allodynia and anxiety-like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu -DRN pathway did not induce mechanical allodynia and anxiety-like behaviors under physiological conditions, but inhibiting this pathway produced anxiety-like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu -DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu -DRN pathway. CONCLUSIONS: The role of rACCGlu -DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu -DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety-like behaviors.

Brain-Computer Interface to Deliver Individualized Multisensory Intervention for Neuropathic Pain.

To unravel the complexity of the neuropathic pain experience, researchers have tried to identify reliable pain signatures (biomarkers) using electroencephalography (EEG) and skin conductance (SC). Nevertheless, their use as a clinical aid to design personalized therapies remains scarce and patients are prescribed with common and inefficient painkillers. To address this need, novel non-pharmacological interventions, such as transcutaneous electrical nerve stimulation (TENS) to activate peripheral pain relief via neuromodulation and virtual reality (VR) to modulate patients' attention, have emerged. However, all present treatments suffer from the inherent bias of the patient's self-reported pain intensity, depending on their predisposition and tolerance, together with unspecific, pre-defined scheduling of sessions which does not consider the timing of pain episodes onset. Here, we show a Brain-Computer Interface (BCI) detecting in real-time neurophysiological signatures of neuropathic pain from EEG combined with SC and accordingly triggering a multisensory intervention combining TENS and VR. After validating that the multisensory intervention effectively decreased experimentally induced pain, the BCI was tested with thirteen healthy subjects by electrically inducing pain and showed 82% recall in decoding pain in real time. Such constructed BCI was then validated with eight neuropathic patients reaching 75% online pain precision, and consequently releasing the intervention inducing a significant decrease (50% NPSI score) in neuropathic patients' pain perception. Our results demonstrate the feasibility of real-time pain detection from objective neurophysiological signals, and the effectiveness of a triggered combination of VR and TENS to decrease neuropathic pain. This paves the way towards personalized, data-driven pain therapies using fully portable technologies.

Peripheral Nerve Stimulation for Pain Management: A Review.

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.