Analgesic effect of apricot kernel oil on neuropathic pain in rats.

Background: A somatosensory nerve lesion or disease causes neuropathic pain. Presently, prescribed treatments are unsatisfactory or ineffective. The kernel oil of the apricot tree (Prunus armeniaca L) is known for its anti-inflammatory and antioxidant effects. This study investigated the effect of apricot kernel oil in chronic constriction injury (CCI)- induced neuropathic pain in rats. Materials/Methods: Liquid chromatography-electrospray mass spectrometry (LC-ESIMS) analysis was carried out to gain a deeper understanding of the apricot kernel oil's main compounds. Rats were treated daily with apricot kernel oil (2 and 4 ml/kg) or gabapentin (100 mg/kg) for 14 days after CCI induction. Hot plate, acetone drop, and Von Frey hair tests were performed to evaluate thermal and mechanical activity. Spinal cord malondialdehyde (MDA), total thiol, interleukin (IL)-1ß, and tumor necrosis factor α (TNF-α) levels were assessed to measure biochemical changes. Results: The most detected compounds in apricot kernel oil were lipids and fatty acids. CCI produced a significant increase in thermal hyperalgesia, mechanical allodynia, and cold allodynia. Moreover, CCI increased the inflammation and oxidative stress markers in spinal cord samples. Oral administration of apricot kernel oil and gabapentin significantly decreased the CCI-induced nociceptive pain threshold. Besides, spinal cord biochemical changes were attenuated. Conclusions: Our findings suggest that apricot kernel oil could attenuate neuropathic pain, possibly through anti-inflammatory and antioxidant properties.

Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.

BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Chronic neuropathic pain components in whiplash-associated disorders correlate with metabolite concentrations in the anterior cingulate and dorsolateral prefrontal cortex: a consensus-driven MRS re-examination.

Introduction: Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Materials and methods: Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Results: Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. Discussion: This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.

microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.

BACKGROUND: Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP. METHODS: NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting. RESULTS: Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p. CONCLUSION: miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.

Spinal nerve transection-induced upregulation of KDM4A in the dorsal root ganglia contributes to the development and maintenance of neuropathic pain via promoting CCL2 expression in rats.

Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs.

The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.

Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.

Association Between Non-spinal Comorbid Medical Conditions and Neuropathic Low Back Pain. - A Further Unravelling of Pain Complexities in the Context of Back Pain.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP) and nociceptive (NoP) low back pain. Traditionally NeP and NoP have been primarily attributed to patho-anatomical abnormalities within the lumbar spine. However, increasing evidence points to multifaceted involvement, encompassing a range of physical, biomechanical, chemical, and psychosocial factors. The study aimed to determine the independent relationship between NeP as assessed by the PainDETECT questionnaire and non-spinal comorbid medical conditions. METHODS: A prospective cohort study was conducted involving 400 patients suffering from chronic LBP (>6months), aged >18 years, who complete the PainDETECT questionnaire and provided responses regarding the presence of any comorbid conditions. A binary logistic regression model was used to analyse the confounding status of comorbid medical conditions and pain severity measured by NRS to determine independent relationships between specific conditions and neuropathic pain. RESULTS: The study included 143 and 257 patients suffering from NeP and NoP, respectively. The NeP group had a 38% higher mean numerical rating scale score compared to the NoP group (8.10 ± 1.55 vs 5.86± 2.26, P < 0.001). The odds of developing NeP were 2.9 Exp(B) = 2.844, 95%C.I. [1.426-5.670], P < 0.01), 2.7 (Exp(B) = 2.726, 95%C.I. [1.183-6.283], P < 0.05) and 2.8 (Exp(B) = 2.847, 95%C.I. [1.473-5.503], P < 0.05) times higher in patients suffering from gastrointestinal conditions, rheumatoid arthritis, and depression, respectively. CONCLUSION: NeP as determined by the PainDETECT questionnaire, is associated with gastrointestinal conditions, rheumatoid arthritis, and depression. This pioneering study has shed light on the potential involvement of the gut microbiome as a common factor connecting non-spinal comorbidities and NeP. These findings underscore the importance of formulating personalized management plans tailored to individual pain and medical profiles, rather than relying on a blanket approach to pain management.

Hyperglycemia-induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis.

BACKGROUND: Hyperglycemia-induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear. OBJECTIVE: To investigate the role of Sirt3, a mitochondrial deacetylase, in hyperglycemia-induced neuroinflammation and DNP and to explore potential therapeutic interventions. METHOD AND RESULTS: Here, we found that Sirt3 was downregulated in spinal dorsal horn (SDH) of diabetic mice by RNA-sequencing, which was further confirmed at the mRNA and protein level. Sirt3 deficiency exacerbated hyperglycemia-induced neuroinflammation and DNP by enhancing microglial aerobic glycolysis in vivo and in vitro. Overexpression of Sirt3 in microglia alleviated inflammation by reducing aerobic glycolysis. Mechanistically, high-glucose stimulation activated Akt, which phosphorylates and inactivates FoxO1. The inactivation of FoxO1 diminished the transcription of Sirt3. Besides that, we also found that hyperglycemia induced Sirt3 degradation via the mitophagy-lysosomal pathway. Blocking Akt activation by GSK69093 or metformin rescued the degradation of Sirt3 protein and transcription inhibition of Sirt3 mRNA, which substantially diminished hyperglycemia-induced inflammation. Metformin in vivo treatment alleviated neuroinflammation and diabetic neuropathic pain by rescuing hyperglycemia-induced Sirt3 downregulation. CONCLUSION: Hyperglycemia induces metabolic reprogramming and inflammatory activation in microglia through the regulation of Sirt3 transcription and degradation. This novel mechanism identifies Sirt3 as a potential drug target for treating DNP.

Case report: safety and efficacy of lidocaine infusion for the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients.

Introduction: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients. Case series presentation: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported. Conclusion: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia.

The effect of intra spinal administration of cerium oxide nanoparticles on central pain mechanism: An experimental study.

This study investigated Cerium oxide nanoparticles (CeONPs) effect on central neuropathic pain (CNP). The compressive method of spinal cord injury (SCI) model was used for pain induction. Three groups were formed by a random allocation of 24 rats. In the treatment group, CeONPs were injected above and below the lesion site immediately after inducing SCI. pain symptoms were evaluated using acetone, Radian Heat, and Von Frey tests weekly for six weeks. Finally, we counted fibroblasts using H&E staining. We evaluated the expression of Cx43, GAD65 and HDAC2 proteins using the western blot method. The analysis of results was done by PRISM software. At the end of the study, we found that CeONPs reduced pain symptoms to levels similar to those observed in normal animals. CeONPs also increased the expression of GAD65 and Cx43 proteins but did not affect HDAC2 inhibition. CeONPs probably have a pain-relieving effect on chronic pain by potentially preserving GAD65 and Cx43 protein expression and hindering fibroblast infiltration.

Polydatin attenuated neuropathic pain and motor dysfunction following spinal cord injury in rats by employing its anti-inflammatory and antioxidant effects.

Background: Considering the complex pathological mechanisms behind spinal cord injury (SCI) and the adverse effects of present non-approved drugs against SCI, new studies are needed to introduce novel multi-target active ingredients with higher efficacy and lower side effects. Polydatin (PLD) is a naturally occurring stilbenoid glucoside recognized for its antioxidative and anti-inflammatory properties. This study aimed to assess the effects of PLD on sensory-motor function following SCI in rats. Methods: Following laminectomy and clip compression injury at the thoracic 8 (T8)-T9 level of the spinal cord, rats were randomly assigned to five groups: Sham, SCI, and three groups receiving different doses of PLD treatment (1, 2, and 3 mg/kg). Over 4 weeks, behavioral tests were done such as von Frey, acetone drop, hot plate, Basso-Beattie-Bresnahan, and inclined plane test. At the end of the study, changes in catalase and glutathione activity, nitrite level, activity of matrix metalloproteinase 2 (MMP2) and MMP9 as well as spinal tissue remyelination/neurogenesis, were evaluated. Results: The results revealed that PLD treatment significantly improved the behavioral performance of the animals starting from the first week after SCI. Additionally, PLD increased catalase, and glutathione levels, and MMP2 activity while reduced serum nitrite levels and MMP9. These positive effects were accompanied by a reduction in the size of the lesion and preservation of neuronal count. Conclusion: In conclusion, PLD showed neuroprotective effects in SCI rats by employing anti-inflammatory and antioxidant effects, through which improve sensory and motor function.

Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients' physical and mental health. Schwann cells (SCs) are the major glial cells of the peripheral nervous system, which play an important role in various inflammatory and metabolic neuropathies by providing nutritional support, wrapping axons and promoting repair and regeneration. Increasingly, high glucose (HG) has been found to promote the progression of DPN pathogenesis by targeting SCs death regulation, thus revealing the specific molecular process of programmed cell death (PCD) in which SCs are disrupted is an important link to gain insight into the pathogenesis of DPN. This paper is the first to review the recent progress of HG studies on apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis pathways in SCs, and points out the crosstalk between various PCDs and the related therapeutic perspectives, with the aim of providing new perspectives for a deeper understanding of the mechanisms of DPN and the exploration of effective therapeutic targets.

Transcriptional reprogramming post-peripheral nerve injury: A systematic review.

Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions.

Determinants of interactions of a novel next-generation gabapentinoid NVA1309 and mirogabalin with the Cavα2δ-1 subunit.

NVA1309 is a non-brain penetrant next-generation gabapentinoid shown to bind Cavα2δ at R243 within a triple Arginine motif forming the binding site for gabapentin and pregabalin. In this study we have compared the effects of NVA1309 with Mirogabalin, a gabapentinoid drug with higher affinity for the voltage-gated calcium channel subunit Cavα2δ-1 than pregabalin which is approved for post-herpetic neuralgia in Japan, Korea and Taiwan. Both NVA1309 and mirogabalin inhibit Cav2.2 currents in vitro and decrease Cav2.2 plasma membrane expression with higher efficacy than pregabalin. Mutagenesis of the classical binding residue arginine R243 and the newly identified binding residue lysine K615 reverse the effect of mirogabalin on Cav2.2 current, but not that of NVA1309.

Neuropathic Pain Masquerading as Dermatologic Symptoms: A Case of Misleading Cutaneous Presentation.

Neuropathic pain presenting as dermatologic symptoms can occur when damaged or dysfunctional nerves manifest with symptoms that resemble skin-related conditions. We present a case of a 62-year-old male who presented with burning pain and redness in the perineum and gluteal cleft. Initially, the patient was treated for dermatologic symptoms, resulting in the resolution of erythema. However, the pain persisted, prompting a neurologic workup. Despite the improvement of skin symptoms, the patient's pain persisted, prompting a neurological workup. Diagnostic imaging revealed significant degenerative changes in the lumbar spine, supporting a neuropathic etiology. This case highlights the importance of considering neurologic disorders in dermatologic practice, especially when cutaneous symptoms persist despite appropriate dermatological treatments.

Single simple question in axonal polyneuropathy.

INTRODUCTION/AIMS: The single simple question (SSQ), "What percentage of normal (0%-100%) do you feel regarding your disease?" has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes. METHODS: A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch-built Overall Disability Scale (RODS). RESULTS: The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = -.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%-70%, and 34% with SSQ >70%). DISCUSSION: The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length-dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP.

Resting-state electroencephalography delta and theta bands as compensatory oscillations in chronic neuropathic pain: a secondary data analysis.

Chronic neuropathic pain (CNP) remains a significant clinical challenge, with complex neurophysiological underpinnings that are not fully understood. Identifying specific neural oscillatory patterns related to pain perception and interference can enhance our understanding and management of CNP. To analyze resting electroencephalography data from individuals with chronic neuropathic pain to explore the possible neural signatures associated with pain intensity, pain interference, and specific neuropathic pain characteristics. We conducted a secondary analysis from a cross-sectional study using electroencephalography data from a previous study, and Brief Pain Inventory from 36 patients with chronic neuropathic pain. For statistical analysis, we modeled a linear or logistic regression by dependent variable for each model. As independent variables, we used electroencephalography data with such brain oscillations: as delta, theta, alpha, and beta, as well as the oscillations low alpha, high alpha, low beta, and high beta, for the central, frontal, and parietal regions. All models tested for confounding factors such as age and medication. There were no significant models for Pain interference in general activity, walking, work, relationships, sleep, and enjoyment of life. However, the model for pain intensity during the past four weeks showed decreased alpha oscillations, and increased delta and theta oscillations were associated with decreased levels of pain, especially in the central area. In terms of pain interference in mood, the model showed high oscillatory Alpha signals in the frontal and central regions correlated with mood impairment due to pain. Our models confirm recent findings proposing that lower oscillatory frequencies, likely related to subcortical pain sources, may be associated with brain compensatory mechanisms and thus may be associated with decreased pain levels. On the other hand, higher frequencies, including alpha oscillations, may disrupt top-down compensatory mechanisms.

H-coil repetitive transcranial magnetic stimulation does not improve executive function in patients with chronic peripheral neuropathic pain: a randomized sham-controlled crossover study.

Introduction: Deep rTMS is an increasingly popular noninvasive brain stimulation technique which has shown promise for treating cognitive impairments. However, few studies have investigated the cognitive effects it could exert in patients with chronic peripheral neuropathic pain. Therefore, we aimed to assess the effects of deep rTMS on executive functioning in patients with peripheral neuropathic pain, in a randomized, double-blind crossover trial. Methods: In total, 17 patients were randomly assigned to receive both active and sham deep H-coil rTMS targeting the primary motor cortex. Each treatment period consisted of five daily rTMS sessions. Selected tests of executive functioning from the CANTAB test battery (paired associates learning, stop signal task, spatial working memory and multitasking test) were performed at baseline, and at 1 week and 3 weeks follow-ups. Results: We did not find any significant interactions between time and treatment for the measures of executive functioning for the patient group, or for patients with reduced cognition compared to normative means. Conclusion: High-frequency deep H-coil rTMS targeting the hand area of the primary motor cortex and delivered over 5 consecutive days did not improve executive functioning in patients with chronic peripheral neuropathic pain. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05488808.

Temporary Gasserian ganglion stimulation utilizing SNM electrode in subacute herpetic trigeminal neuralgia.

Objective: Gasserian ganglion stimulation (GGS) is a neuromodulation technique that has been extensively applied in treating postherpetic trigeminal neuralgia. However, permanent implantation of GGS was preferred in most treatment approaches. Few studies have investigated temporary GGS for the treatment of acute/subacute herpetic trigeminal neuralgia. Moreover, previous research has reported lead dislocation when utilizing traditional electrodes, which was associated with poor pain relief. In GGS research, preventing the accidental displacement of lead following implantation has consistently been a primary objective. Methods: We report a case of a 70-year-old woman with subacute herpetic trigeminal neuralgia who underwent temporary GGS for 14 days utilizing a sacral neuromodulation (SNM) quadripolar-tined lead. Computed tomography-guided percutaneous foramen ovale (FO) puncture and temporary SNM electrode implantation were performed during the surgery. A telephone interview was conducted to record a 12-month follow-up. Results: At admission, zoster-related trigeminal pain severity was assessed to be 9/10 on the visual analog scale (VAS). After a 14-day GGS treatment, the pain assessed on the VAS score reduced to 1/10 at discharge but increased to 4/10 at the 12-month follow-up after surgery. Additionally, the anxiety level improved from 58 points to 35 points on the Self-Rating Anxiety Scale (SAS), and the depression level improved from 62 points to 40 points on the Self-Rating Depression Scale (SDS). The Physical Component Summary score of the 12-item Short-Form Health Survey (SF-12) increased from 33.9 to 47.0, and the Mental Component Summary (MCS) score of the SF-12 increased from 27.4 to 41.9. Conclusion: Temporary GGS might be a potentially effective treatment for subacute herpetic trigeminal neuralgia, and an SNM electrode might be a good choice for reducing the risk of dislocation.

Clinical Benefits and Safety of Medical Cannabis Products: A Narrative Review on Natural Extracts.

Interest in medical cannabis and cannabis-based medicinal products (CBMPs) has increased greatly in recent years. Two cannabinoids are of principal importance; delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive component, and also cannabidiol (CBD), considered non-intoxicating. Each has distinct mechanisms of action and different therapeutic potentials. CBMPs differ in their ∆9-THC and CBD components; predominantly ∆9-THC, balanced formulations with equivalent ∆9-THC and CBD elements, and CBD-predominant products. In this narrative review, we evaluate the published evidence for the clinical benefits of CBMPs and overall benefits in well-being. We also review the overall safety profile and discuss the potential for dependence with CBMPs. Evidence can be drawn from a wide range of randomized and other controlled studies and from observational real-world studies. Most data from observational registry studies are supportive of ∆9-THC-based products (∆9-THC-predominant or balanced CBMPs) in the management of chronic neuropathic pain. Balanced products are also effective in reducing spasticity in multiple sclerosis. Most CBMPs show benefit in providing symptomatic benefits in reducing anxiety, nausea, and in improving sleep, but the place of specific products is more subtle, and choice guided by specific circumstances. Symptomatic improvements are accompanied by improved quality of life and well-being. Safety data indicate that CBMPs are generally well tolerated in most patients without specific contraindications. The majority of adverse effects are non-serious, and transient; most are principally associated with ∆9-THC and are dose-dependent. In contrast to recreational cannabis use, there is little evidence from clinical studies that CBMPs have any potential for dependence.