The glossopharyngeal nerve (IX cranial nerve pair): anatomical considerations and neuralgia: literature review / O nervo glossofaringeo (IX par de nervo craniano): considerações anatômicas e neuralgia: revisão da literatura

The glossopharyngeal nerve (IX cranial nerve) is a mixed nerve, with both motor and sensory function. This relates to the tongue and pharynx. Glossopharyngeal neuralgia is a rare nervous neuropathy, with poristic, lancinating and paritary crises, usually unilateral. The aim of the study was to review the literature on glossopharyngeal neuralgia of the nerve (IX cranial nerve), highlighting the anatomical aspects of this nerve and the possible causes and complications of neuralgia as well as forms of treatment. A literature review was carried out in the international Pubmed database. The literature review included 72 articles from 2015 to 2021. The keywords used were: "anatomy of glossopharyngeal neuralgia". Of the 72 articles, 7 were used for this literature review. Uncommon as nervous/glossophingeal etiologies and pathologies are neurological abnormalities/neurovarises and pathologies are neurovascular/neurovariseal lesions. Pharmacological treatment approaches mentioned in the literature were therapy with antiepileptics and antidepressants such as carbamazepine and gabapentin; a microvascular decompression; and gamma knife radiosurgery(AU)

O nervo glossofaríngeo (IX par de nervo craniano) é um nervo misto, contendo função tanto motora como sensitiva. Este nervo relaciona-se com a língua e com a faringe. A neuralgia do nervo glossofaríngeo é uma neurapatia rara, sendo caracterizada por crises dolorosas, lancinantes e paroxísticas, geralmente unilaterais. O objetivo do estudo foi realizar uma revisão de literatura sobre a neuralgia do nervo glossofaríngeo (IX par de nervo craniano), destacando os aspectos anatômicos deste nervo e as possíveis causas e complicações da neuralgia bem como formas de tratamento. Foi realizada uma revisão da literatura na base de dados internacional Pubmed. A revisão da literatura incluiu 72 artigos no período de 2015 a 2021. As palavras-chave utilizadas foram: "anatomia da neuralgia do glossofaríngeo". Dos 72 artigos, 7 foram utilizados para esta revisão de literatura. Verificouse que a neuralgia do nervo glossofaríngeo é incomum e as etiologias mais encontradas foram compressão neurovascular/variações vasculares, patologias e traumas. As abordagens dos tratamentos mencionadas na literatura foram a terapia farmacológica da área com antiepilépticos e antidepressivos, como carbamazepina e gabapentina; a descompressão microvascular; e radiocirurgia com faca gama(AU)

Peripheral Nerve Stimulation for Chronic Intractable Neuropathic Pain Following a Brachial Plexus Avulsion Injury: A Case Report.

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.

High-voltage, Long-duration Pulsed Radiofrequency to the Dorsal Root Ganglion Provides Improved Pain Relief for Herpes Zoster Neuralgia in the Subacute Stage.

BACKGROUND: Postherpetic neuralgia (PHN) is pain persisting beyond 3 months from rash onset and is the most common complication of herpes zoster (HZ); it is commonly refractory to medication treatment. Available evidence indicates that high-voltage, long-duration pulsed radiofrequency (PRF) to the dorsal root ganglion (DRG) is a novel and effective treatment for this complication. Nevertheless, the effects of this intervention on refractory HZ neuralgia less than 3 months have not been evaluated. OBJECTIVE: The objective of this study was to assess the therapeutic efficacy and safety of high-voltage, long-duration PRF to the DRG for patients with subacute HZ neuralgia compared with that of patients with PHN. STUDY DESIGN: A retrospective comparative research. SETTING: Hospital department in China. METHODS: Sixty-four patients with HZ neuralgia in different stages receiving high-voltage, long-duration PRF to the DRG were included. According to the days from zoster onset to PRF implementation, they were divided into the subacute (one to 3 months) or PHN group (more than 3 months). The therapeutic effect was evaluated by pain relief using the Numeric Rating Scale at one day, one week, one month, 3 months, and 6 months post-PRF. The five-point Likert scale measured patient satisfaction. Post-PRF side effects were also recorded to determine the safety of the intervention. RESULTS: The intervention significantly reduced pain in all patients, but pain relief at one month, 3 months, and 6 months post-PRF was better in the subacute group than in the PHN group. Furthermore, the success rate of PRF was significantly increased in the subacute group compared with the PHN group (81.3% vs 56.3%, P = 0.031). There was no significant difference in patient satisfaction at 6 months between groups. LIMITATIONS: This is a single-center retrospective study with a small sample size. CONCLUSIONS: High-voltage, long-duration PRF to the DRG is effective and safe for HZ neuralgia in different stages, and can provide an improved pain relief for HZ neuralgia in the subacute stage.

Neuropathic Pain Was Associated with Central Sensitivity Syndrome in Patients with Preoperative Lumbar Spinal Stenosis Using the painDETECT and Central Sensitization Inventory Questionnaires: A Cross-Sectional Study.

Background: Lumbar spinal stenosis (LSS) patients have been reported to have neuropathic pain and central sensitivity syndrome (CSS). These associations have been reported in other diseases but are unknown in preoperative LSS patients. We aimed to investigate the association between neuropathic pain and CSS in preoperative LSS patients using the painDETECT and the Central Sensitization Inventory (CSI) questionnaires. Methods: This cross-sectional study was conducted from November 2021 to March 2022. The data were collected regarding demographics and pain, including neuropathic pain, numbness, LSS severity, physical function, quality of life, and CSS. Patients were divided into two groups, patients with acute and chronic pain, and further classified into three categories based on the clinical phenotype of patients in each group. Independent variables included age, gender, type of LSS (bilateral or unilateral symptoms), Numerical Rating Scale of leg pain, CSI, and the Zurich Claudication Questionnaire (ZCQ) for symptom severity and physical function. The dependent variable was painDETECT. Multiple regression analysis using the forced entry method examined the association between painDETECT and CSI. Results: Of the 119 patients with preoperative LSS, 106 were included. The mean age of the participants was 69.9 years, and 45.3% were female. Neuropathic pain was present in 19.8%, and CSS was present in 10.4%. The CSI (ß = 0.468, p < 0.001) and ZCQ for symptom severity (ß = 0.304, p < 0.01) were significantly associated with the painDETECT, explaining 47.8% of the variance in the painDETECT score. Conclusions: There is an association between neuropathic pain and CSS in patients with preoperative LSS using the painDETECT and CSI questionnaires.

Repetitive transcranial magnetic stimulation regulates neuroinflammation in neuropathic pain.

Neuropathic pain (NP) is a frequent condition caused by a lesion in, or disease of, the central or peripheral somatosensory nervous system and is associated with excessive inflammation in the central and peripheral nervous systems. Repetitive transcranial magnetic stimulation (rTMS) is a supplementary treatment for NP. In clinical research, rTMS of 5-10 Hz is widely placed in the primary motor cortex (M1) area, mostly at 80%-90% RMT, and 5-10 treatment sessions could produce an optimal analgesic effect. The degree of pain relief increases greatly when stimulation duration is greater than 10 days. Analgesia induced by rTMS appears to be related to reestablishing the neuroinflammation system. This article discussed the influences of rTMS on the nervous system inflammatory responses, including the brain, spinal cord, dorsal root ganglia (DRG), and peripheral nerve involved in the maintenance and exacerbation of NP. rTMS has shown an anti-inflammation effect by decreasing pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, and increasing anti-inflammatory cytokines, including IL-10 and BDNF, in cortical and subcortical tissues. In addition, rTMS reduces the expression of glutamate receptors (mGluR5 and NMDAR2B) and microglia and astrocyte markers (Iba1 and GFAP). Furthermore, rTMS decreases nNOS expression in ipsilateral DRGs and peripheral nerve metabolism and regulates neuroinflammation.

A randomized, active-controlled, parallel, open-label, multicenter, phase 4 study to compare the efficacy and safety of pregabalin sustained release tablet and pregabalin immediate release capsule in type II diabetic patients with peripheral neuropathic pain.

BACKGROUND: Diabetic peripheral polyneuropathy is the most common chronic complication of type 2 diabetes. Neuropathic pain is challenging to manage, and various drugs are required to control it, decreasing treatment adherence. Pregabalin, a ligand that binds to alpha-2-delta subunits of the presynaptic calcium channel, has been approved by the Food and Drug Administration for the treatment of diabetic neuropathic pain. In this study, we will compare the efficacy, safety, treatment satisfaction, and compliance between pregabalin sustained-release (SR) tablets and pregabalin immediate-release (IR) capsules in type 2 diabetic patients with peripheral neuropathic pain. METHODS: This study is a randomized, active-controlled, parallel, open-label, multicenter, phase 4 clinical trial (trial registration NCT05624853). Type 2 diabetic patients with glycosylated hemoglobin below 10% and peripheral neuropathic pain who have been taking pregabalin 150 mg/d or more for more than 4 weeks will be randomly assigned to pregabalin SR tablet (150 mg once a day, n = 65) or pregabalin IR capsule (75 mg twice a day, n = 65) therapy for 8 weeks. The primary outcome will be the efficacy of SR pregabalin after 8 weeks of treatment, which will be assessed by visual analog scale measurements. The secondary outcomes will include changes in several parameters, such as quality of life, treatment satisfaction, quality of sleep, and drug compliance. DISCUSSION: In thus study, we aim to demonstrate that pregabalin SR tablets are associated with better compliance and satisfaction compared with pregabalin IR capsules, despite similar efficacy.

A Pilot Study of Autonomic Function Screening Tests for Differentiating Complex Regional Pain Syndrome Type II and Traumatic Neuropathic Pain.

Background and Objectives: One of the most challenging tasks in a clinical setting is to differentiate between complex regional pain syndrome (CRPS) type II and traumatic neuropathic pain (NeP). CRPS is characterized by several dysautonomic manifestations, such as edema, hyper/hypohidrosis, skin color change, and tachycardia. This study compared the outcomes of autonomic function screening tests in patients with CRPS type II and traumatic NeP for diagnostic differentiation. Materials and Methods: CRPS type II was diagnosed according to the Budapest research criteria, while NeP was diagnosed according to the updated grading system suggested by the International Association for the Study of Pain Special Interest Group on Neuropathic Pain in 2016. Twenty patients with CRPS type II and twenty-five with traumatic NeP were investigated. Results: Twelve patients with CRPS type II presented abnormal results for the quantitative sudomotor axon reflex test (QSART). Abnormal QSART results were more common in the CRPS type II group. Conclusions: Analysis of QSART combined with other ancillary tests can help in the differential diagnosis of CRPS type II and traumatic NeP if factors influencing abnormal QSART are sufficiently controlled.

Anti-Inflammatory Activity of Synaptamide in the Peripheral Nervous System in a Model of Sciatic Nerve Injury.

N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the present study, we examine the effect of synaptamide on the peripheral nervous system in a neuropathic pain condition. The dynamics of ionized calcium-binding adapter molecule 1 (iba-1), CD68, CD163, myelin basic protein, and the production of interleukin 1ß and 6 within the sciatic nerve, as well as the neuro-glial index and the activity of iba-1, CD163, glial fibrillary acidic protein (GFAP), neuronal NO synthase (nNOS), substance P (SP), activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), are studied. According to our results, synaptamide treatment (4 mg/kg/day) (1) decreases the weight-bearing deficit after nerve trauma; (2) enhances the remyelination process in the sciatic nerve; (3) shows anti-inflammatory properties in the peripheral nervous system; (4) decreases the neuro-glial index and GFAP immunoreactivity in the DRG; (5) inhibits nNOS- and SP-ergic activity in the DRG, which might contribute to neuropathic pain attenuation. In general, the current study demonstrates the complex effect of synaptamide on nerve injury, which indicates its high potential for neuropathic pain management.

Lesional Antibody Synthesis and Complement Deposition Associate With De Novo Antineuronal Antibody Synthesis After Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Spinal cord injury (SCI) disrupts the fine-balanced interaction between the CNS and immune system and can cause maladaptive aberrant immune responses. The study examines emerging autoantibody synthesis after SCI with binding to conformational spinal cord epitopes and surface peptides located on the intact neuronal membrane. METHODS: This is a prospective longitudinal cohort study conducted in acute care and inpatient rehabilitation centers in conjunction with a neuropathologic case-control study in archival tissue samples ranging from acute injury (baseline) to several months thereafter (follow-up). In the cohort study, serum autoantibody binding was examined in a blinded manner using tissue-based assays (TBAs) and dorsal root ganglia (DRG) neuronal cultures. Groups with traumatic motor complete SCI vs motor incomplete SCI vs isolated vertebral fracture without SCI (controls) were compared. In the neuropathologic study, B cell infiltration and antibody synthesis at the spinal lesion site were examined by comparing SCI with neuropathologically unaltered cord tissue. In addition, the CSF in an individual patient was explored. RESULTS: Emerging autoantibody binding in both TBA and DRG assessments was restricted to an SCI patient subpopulation only (16%, 9/55 sera) while being absent in vertebral fracture controls (0%, 0/19 sera). Autoantibody binding to the spinal cord characteristically detected the substantia gelatinosa, a less-myelinated region of high synaptic density involved in sensory-motor integration and pain processing. Autoantibody binding was most frequent after motor complete SCI (grade American Spinal Injury Association impairment scale A/B, 22%, 8/37 sera) and was associated with neuropathic pain medication. In conjunction, the neuropathologic study demonstrated lesional spinal infiltration of B cells (CD20, CD79a) in 27% (6/22) of patients with SCI, the presence of plasma cells (CD138) in 9% (2/22). IgG and IgM antibody syntheses colocalized to areas of activated complement (C9neo) deposition. Longitudinal CSF analysis of an additional single patient demonstrated de novo (IgM) intrathecal antibody synthesis emerging with late reopening of the blood-spinal cord barrier. DISCUSSION: This study provides immunologic, neurobiological, and neuropathologic proof-of-principle for an antibody-mediated autoimmunity response emerging approximately 3 weeks after SCI in a patient subpopulation with a high demand of neuropathic pain medication. Emerging autoimmunity directed against specific spinal cord and neuronal epitopes suggests the existence of paratraumatic CNS autoimmune syndromes.

[Post-traumatic pain mononeuropathies]. / Posttravmaticheskie bolevye mononeiropatii.

Neuropathic pain syndrome (NPS) caused by peripheral nerve (PN) injury is a serious clinical problem due to its prevalence, complexity of pathogenesis, significant impact on the quality of life of patients. The issues of epidemiology, pathogenesis and treatment of patients with NBS with PN injury are considered. Modern possibilities of invasive treatment of such patients are discussed.

Preparation of Primary Mixed Glial Cell Cultures from Adult Mouse Spinal Cord Tissue.

Central nervous system glial cells are known to mediate many neurocognitive/neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Similar glial responses have been recognized as critical factors contributing to the development of diseases in the peripheral nervous system, including various types of peripheral neuropathies, such as peripheral nerve injury-induced neuropathic pain, diabetic neuropathy, and HIV-associated sensory neuropathy. Investigation of the central mechanisms of these peripherally-manifested diseases often requires the examination of spinal cord glial cells at cellular/molecular levels in vitro. When using rodent models to study these diseases, many investigators have chosen to use neonatal cerebral cortices to prepare glial cultures or immortalized cell lines in order to obtain sufficient numbers of cells for assessment. However, differences in responses between cell lines versus primary cultures, neonatal vs. adult cells, and brain vs. spinal cord cells may result in misleading data. Here, we describe a protocol for preparing mixed glial cells from adult mouse spinal cord that can be used for direct in vitro evaluations or further preparation of microglia-enriched and microglia-depleted cells. In this protocol, spinal cord tissue is enzymatically dissociated and adult mixed glial cells are ready to be used between 12 and 14 days after the establishment of the culture. This protocol may be further refined to prepare spinal cord glial cells from spinal cord tissues of adult rats and potentially other species. Mixed glial cultures can be prepared from animals of different strains or post-in vivo manipulations and therefore are suitable for studying a variety of diseases/disorders that involve spinal cord pathological changes, such as amyotrophic lateral sclerosis and multiple sclerosis, as well as toxin-induced changes. © 2023 Wiley Periodicals LLC. Basic Protocol: Preparation of primary mixed glial cell cultures from adult mouse spinal cord tissue.

Considerations on the Obstacles That Lead to Slow Recruitment in a Pain Management Clinical Trial: Experiences from the Belgian PELICAN (PrEgabalin Lidocaine Capsaicin Neuropathic Pain) Pragmatic Study.

Background: A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life. Objective: Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome. Methods: A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment. Results: Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified. Conclusion: The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase. Clinical Trials. This trial is registered with NCT03348735. EUDRACT number 2018-003617-17.

Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain.

Pain, although unpleasant, is an essential warning mechanism against injury and damage of the organism. An intricate network of specialised sensors and transmission systems contributes to reception, transmission and central sensitization of pain. Here, we briefly introduce some of the main aspects of pain signal transmission, including nociceptors and nociceptive signals, mechanisms of inflammatory and neuropathic pain, and the situation of diabetes-associated neuropathic pain. The role of glia-astrocytes, microglia, satellite glia cells-and their specific channels, transporters and signaling pathways is described. A focus is on the contribution of inhibitory synaptic signaling to nociception and a possible role of glycine receptors in glucose-mediated analgesia and treatment-induced diabetic neuropathy. Inhibitory receptors such as GABAA- and glycine receptors are important contributors to nociceptive signaling; their contribution to altered pain sensation in diabetes may be of clinical relevance, and they could be promising therapeutic targets towards the development of novel analgesics.

ATP-releasing SWELL1 channel in spinal microglia contributes to neuropathic pain.

Following peripheral nerve injury, extracellular adenosine 5'-triphosphate (ATP)-mediated purinergic signaling is crucial for spinal cord microglia activation and neuropathic pain. However, the mechanisms of ATP release remain poorly understood. Here, we show that volume-regulated anion channel (VRAC) is an ATP-releasing channel and is activated by inflammatory mediator sphingosine-1-phosphate (S1P) in microglia. Mice with microglia-specific deletion of Swell1 (also known as Lrrc8a), a VRAC essential subunit, had reduced peripheral nerve injury-induced increase in extracellular ATP in spinal cord. The mutant mice also exhibited decreased spinal microgliosis, dorsal horn neuronal hyperactivity, and both evoked and spontaneous neuropathic pain-like behaviors. We further performed high-throughput screens and identified an FDA-approved drug dicumarol as a novel and potent VRAC inhibitor. Intrathecal administration of dicumarol alleviated nerve injury-induced mechanical allodynia in mice. Our findings suggest that ATP-releasing VRAC in microglia is a key spinal cord determinant of neuropathic pain and a potential therapeutic target for this debilitating disease.

Diagnosis, management and impact of painful diabetic peripheral neuropathy: A patient survey in four European countries.

AIMS: The aim of this study was to assess patient perspectives and experiences of the impact of neuropathic pain, painful diabetic neuropathy (pDPN) diagnosis and treatment, and the patient-healthcare professional (HCP) relationship. METHODS: We conducted a quantitative online survey in Germany, the Netherlands, Spain, and the UK among adults with diabetes who responded "yes" to at least four of ten questions of in the Douleur Neuropathique en 4 Questions (DN4) questionnaire. RESULTS: Of 3626 respondents, 576 met the eligibility criteria. Daily pain was rated as moderate or severe by 79 % of respondents. Most participants reported a negative impact of their pain on sleep (74 %), mood (71 %), exercise (69 %), concentration (64 %) and daily activities (62 %), and 75 % of those in employment had missed work because of their pain in the past year. Overall, 22 % of respondents avoided discussing pain with their HCP, 50 % had not received formal pDPN diagnosis, and 56 % had not used prescribed pain medications. Although two-thirds (67 %) of respondents reported feeling satisfied or very satisfied with treatment, 82 % of these patients still experienced daily moderate or severe pain. CONCLUSIONS: Neuropathic pain in people with diabetes affects daily life and remains underdiagnosed and undertreated in clinical practice.

Pain assessment 3 × 3: a clinical reasoning framework for healthcare professionals.

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.

Prevalence of polyneuropathies among systemic sclerosis patients and impact on health-related quality of life.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic rheumatic disease that affects multiple organ systems, including the peripheral nervous system. However, studies into the involvement of polyneuropathies (PNP) have shown inconsistent results. The aim of this study was to determine the prevalence of small (SFN) and large (LFN) fibre neuropathy among SSc patients and the impact on health-related quality of life (HRQoL). MATERIAL AND METHODS: The study enrolled 67 patients with diagnosed SSc. The severity of neuropathic symptoms was evaluated using shortened and revised total neuropathy scoring criteria. Nerve conduction studies were used for LFN, and quantitative sensory testing was used to evaluate SFN. Neuropathic pain was evaluated using a Douleur Neuropathique en 4 questionnaire, and the severity of anxiety symptoms was assessed using a Generalised Anxiety Disorder-7 scale. The Health Assessment Questionnaire-Disability Index was used to assess HRQoL. Previous data on antinuclear autoantibodies (ANA) test results was obtained. Statistical analysis was performed using SPSS software. RESULTS: LFN was diagnosed in 47.8% (n = 32/67) and SFN in 40.3% (n = 27/67) of the subjects. ANA positivity was not associated with the presence of LFN/SFN. The severity of neuropathic pain had a significant correlation with anxiety symptoms (r = 0.61, p < 0.001), the severity of neuropathy symptoms (r = 0.51, p < 0.001) and HRQoL (r = 0.45, p < 0.001). The severity of neuropathy symptoms correlated with HRQoL (r = 0.39, p = 0.001). CONCLUSIONS: We demonstrated that PNP are found in almost all SSc patients. Also, SFN is as common as LFN. Additionally, we found that the severity of neuropathy symptoms and neuropathic pain are both associated with a worse HRQoL.

The Downregulation of Opioid Receptors and Neuropathic Pain.

Neuropathic pain (NP) refers to pain caused by primary or secondary damage or dysfunction of the peripheral or central nervous system, which seriously affects the physical and mental health of 7-10% of the general population. The etiology and pathogenesis of NP are complex; as such, NP has been a hot topic in clinical medicine and basic research for a long time, with researchers aiming to find a cure by studying it. Opioids are the most commonly used painkillers in clinical practice but are regarded as third-line drugs for NP in various guidelines due to the low efficacy caused by the imbalance of opioid receptor internalization and their possible side effects. Therefore, this literature review aims to evaluate the role of the downregulation of opioid receptors in the development of NP from the perspective of dorsal root ganglion, spinal cord, and supraspinal regions. We also discuss the reasons for the poor efficacy of opioids, given the commonness of opioid tolerance caused by NP and/or repeated opioid treatments, an angle that has received little attention to date; in-depth understanding might provide a new method for the treatment of NP.

Curcumin promotes microglial M2 polarization and suppresses chronic constriction: Injury-induced neuropathic pain in a rat model of peripheral neuropathy.

OBJECTIVES: Glia (i.e., astrocyte and microglia) activation in the central nervous system plays a critical role in developing neuropathic pain. Microglia can be activated into proinflammatory (M1) and anti-inflammatory (M2) phenotypes. Switching microglial polarization from M1 to M2 phenotypes represents a novel therapeutic strategy for neuropathic pain. Curcumin has been widely used for its anti-inflammatory and immunomodulatory effects. This study investigated effects of curcumin on astrocyte activation and microglia polarization in the cuneate nucleus (CN) and development of neuropathic pain behavior after chronic constriction injury (CCI) of the median nerve. METHODS: Rats were fed with curcumin once daily at a dose of 40, 80, or 120 mg/kg 30 min before and until 7 d after median nerve CCI. Subsequently, mechanical allodynia and thermal hyperalgesia were evaluated using von Frey filaments and plantar tests, respectively. The levels of astrocyte marker, monoclonal glial fibrillary acidic protein; microglia marker, ionized calcium-binding adapter molecule 1; M1 marker, CD86; and M2 marker, CD206 in the cuneate nucleus were determined. Enzyme-linked immunosorbent assay was applied to measure cytokine concentrations. RESULTS: Curcumin administration dose-dependently reduced mechanical allodynia and thermal hyperalgesia and decreased monoclonal glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 immunoreactivity in the ipsilateral cuneate nucleus after CCI. On ultrastructural observation, curcumin treatment was associated with fewer features of activated astrocytes and microglia. Furthermore, CCI rats given curcumin exhibited a decline in CD86 immunoreactivity and proinflammatory cytokine levels but an increase in CD206 immunoreactivity and release of anti-inflammatory cytokines. CONCLUSIONS: In our findings, curcumin switches microglial phenotypes from M1 to M2 by suppressing astrocytic activation, reducing proinflammatory cytokine release, promoting anti-inflammatory cytokine production, and contributing to relief of neuropathic pain.