Platelet-rich plasma alleviates neuropathic pain in osteoarthritis by downregulating microglial activation.

BACKGROUND: The development of neuropathic pain (NP) is one of the reasons why the pain is difficult to treat, and microglial activation plays an important role in NP. Recently, platelet-rich plasma (PRP) has emerged as a novel therapeutic method for knee osteoarthritis (KOA). However, it's unclarified whether PRP has analgesic effects on NP induced by KOA and the underlying mechanisms unknown. PURPOSE: To observe the analgesic effects of PRP on NP induced by KOA and explore the potential mechanisms of PRP in alleviating NP. METHODS: KOA was induced in male rats with intra-articular injections of monosodium iodoacetate (MIA) on day 0. The rats received PRP or NS (normal saline) treatment at days 15, 17, and 19 after modeling. The Von Frey and Hargreaves tests were applied to assess the pain-related behaviors at different time points. After euthanizing the rats with deep anesthesia at days 28 and 42, the corresponding tissues were taken for subsequent experiments. The expression of activating transcription factor 3 (ATF3) in dorsal root ganglia (DRG) and ionized-calcium-binding adapter molecule-1(Iba-1) in the spinal dorsal horn (SDH) was detected by immunohistochemical staining. In addition, the knee histological assessment was performed by hematoxylin-eosin (HE) staining. RESULTS: The results indicated that injection of MIA induced mechanical allodynia and thermal hyperalgesia, which could be reversed by PRP treatment. PRP downregulated the expression of ATF3 within the DRG and Iba-1 within the SDH. Furthermore, an inhibitory effect on cartilage degeneration was observed in the MIA + PRP group only on day 28. CONCLUSION: These results indicate that PRP intra-articular injection therapy may be a potential therapeutic agent for relieving NP induced by KOA. This effect could be attributed to downregulation of microglial activation and reduction in nerve injury.

Neuropathic pain in cats: Mechanisms and multimodal management.

PRACTICAL RELEVANCE: Chronic pain is a significant welfare concern in cats, and neuropathic pain, which arises from aberrant processing of sensory signals within the nervous system, is a subcategory of this type of pain. To comprehend this condition and how multimodal pharmacotherapy plays a central role in alleviating discomfort, it is crucial to delve into the anatomy of nociception and pain perception. In addition, there is an intricate interplay between emotional health and chronic pain in cats, and understanding and addressing the emotional factors that contribute to pain perception, and vice versa, is essential for comprehensive care.Clinical approach:Neuropathic pain is suspected if there is abnormal sensation in the area of the distribution of pain, together with a positive response to trial treatment with drugs effective for neuropathic pain. Ideally, this clinical suspicion would be supported by confirmation of a lesion at this neurolocalisation using diagnostic modalities such as MRI and neuroelectrophysiology. Alternatively, there may be a history of known trauma at that site. A variety of therapies, including analgesic, anti-inflammatory and adjuvant drugs, and neuromodulation (eg, TENS or acupuncture), can be employed to address different facets of pain pathways.Aim:This review article, aimed at primary care/ general practitioners, focuses on the identification and management of neuropathic pain in cats. Three case vignettes are included and a structured treatment algorithm is presented to guide veterinarians in tailoring interventions.Evidence base:The review draws on current literature, where available, along with the author's extensive experience and research.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Research trends on acupuncture for neuropathic pain: A bibliometric analysis from 1979 to 2023.

BACKGROUND: Acupuncture has drawn increasing attention as a complementary and alternative therapy for neuropathic pain (NP). The present study aimed to summarize the current status and research trends on acupuncture for NP over the past several decades. METHODS: The publications on acupuncture for NP in the database of Web of Science Core Collection from 1979 to 2023 were searched. VOSviewer (1.6.15) and CiteSpace software (5.5.R2) were applied to identify active authors, journals, countries and institutions, co-cited references and hot keywords. RESULTS: A total of 642 publications were finally included, and the quantitative trend of annual publications on acupuncture for NP have shown overall upward from 1979 to 2023. Peoples R China was the most productive and influential country, while Kyung Hee University from South Korea was both the first in publications and citations. Fang JQ ranked the first productive author and Han JS was the first 1 among the co-cited authors. The first productive journal was Evidence-based Complementary and Alternative Medicine, while the first co-cited journal was Pain. The high-frequency keywords were divided into 9 clusters, and the frontier topic focused on "Chronic pain". CONCLUSION: This present study visually showed the research status and trends of acupuncture for NP from 1979 to 2023 on the basis of bibliometric analysis, which may in some way help researcher discovery and explore some new research directions and ideas in the future.

Radiofrequency regulation of the sphenopalatine ganglion in managing herpes zoster ophthalmicus neuralgia: A case series.

INTRODUCTION: Trigeminal herpes zoster, which comprises 10% to 20% of cases of herpes zoster, often leads to severe pain in the ophthalmic branches. Current treatments, including drug therapy and minimally invasive interventions, have limitations; accordingly, there is a need to explore alternative approaches. This study aimed to evaluate the efficacy and safety of computerized tomography (CT)-guided pulsed radiofrequency of the sphenopalatine ganglion in patients with intractable trigeminal herpetic pain. PATIENT CONCERNS: Three patients with intractable trigeminal ophthalmic zoster neuralgia were studied. All patients complained of bursts of headache, which occurred at least 10 times a day, usually in the periorbital and frontal regions. Conventional treatments, including oral medications and radiofrequency therapy targeting the trigeminal-semilunar ganglion and supraorbital nerve, could not sufficiently provide relief. DIAGNOSIS: Two patients were diagnosed with herpes zoster in the ocular branch of the trigeminal nerve with conjunctivitis, while one patient was diagnosed with postherpetic neuralgia in the ocular branch of the trigeminal nerve. INTERVENTIONS: This study employed a novel approach that involved CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion. OUTCOMES: In all three patients, pain relief was achieved within 1 to 3 days after treatment. During the follow-up, one patient had pain recurrence; however, its severity was ≈ 40% lower than the pretreatment pain severity. The second patient had sustained and effective pain relief. However, the pain of the third patient worsened again after 2 months. The average follow-up duration was 3 months. None of the enrolled patients showed treatment-related adverse reactions or complications. CONCLUSION: Our findings indicated that CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion was a safe and effective intervention for pain in patients with trigeminal ophthalmic zoster neuralgia, suggesting that it may be a therapeutic option if other treatments fail.

Cranial Neuralgias.

OBJECTIVE: The cranial neuralgias are relatively rare, but recognizing these syndromes and distinguishing among them is critical to reducing unnecessary pain and disability for affected patients. Despite their distinctive features, cranial neuralgias may go undiagnosed or misdiagnosed for several years. A notable proportion of cranial neuralgia presentations are due to secondary causes and require targeted treatment. The purpose of this article is to review the diagnosis and management of cranial neuralgias encountered in clinical practice. LATEST DEVELOPMENTS: In 2020, the International Classification of Orofacial Pain was released for the first time. Modeled after the International Classification of Headache Disorders, it includes updated terminology for cranial neuralgias. The underlying pathophysiology of the cranial neuralgias is currently believed to be rooted in both peripheral and central nociceptive systems. In addition, a growing number of familial cases are being identified. Recent therapeutic advancements include a better understanding of how to utilize older therapies and procedures more effectively as well as the development of newer approaches. ESSENTIAL POINTS: Cranial neuralgia syndromes are rare but important to recognize due to their debilitating nature and greater likelihood of having potentially treatable underlying causes. While management options have remained somewhat limited, scientific inquiry is continually advancing the understanding of these syndromes and how best to address them.

Peripheral nerve stimulation (PNS): A valid and definitive therapeutical option for a case of anterior cutaneous nerve entrapment syndrome (ACNES).

Anterior cutaneous nerve entrapment syndrome (ACNES) is a cause of moderate to severe chronic pain, hyperesthesia/hypoesthesia, and altered perception of heat/cold in a specific region of the anterior abdominal wall, referable to the territory of innervation of one or more anterior branches of the intercostal nerves. None of the therapeutic options currently available has proved to be effective in the long term or decisive. In recent years, we have begun to treat purely sensory neuropathies, such as this, with the implantation of wireless peripheral nerve stimulators (PNS), achieving the safety of modular and personalized analgesia. We report the case of a 41-year-old man suffering from ACNES of the 8th intercostal nerve for two years. We first performed two consecutive ultrasound-guided diagnostic blocks of the anterior cutaneous branch of the 8th intercostal right nerve and then elected the patient for ultrasound-guided nerve decompression followed by neuromodulation and pulsed-radiofrequency (PRF). Taking into account full employment, young age, and the likelihood of having to repeat the treatment several times, we considered him for Peripheral Nerve Stimulation (PNS) implantation under ultrasound guidance, and we implanted the wireless lead at the anterior branch of the right 8th intercostal nerve, and programmed tonic stimulation 100 Hz PW 200 ms. The patient reported immediate pain relief and never took medication for this problem again, at two years follow-up. PNS has had an increasing role in the management of chronic neuropathic pain, especially in merely sensitive neuropathies like ACNES. We support future research on this theme.

Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway.

The role of circular RNAs (circRNAs) in neuropathic pain is linked to the fundamental physiological mechanisms involved. However, the exact function of circRNAs in the context of neuropathic pain is still not fully understood. The functional impact of circGRIN2B on the excitability of dorsal root ganglion (DRG) neurons was investigated using siRNA or overexpression technology in conjunction with fluorescence in situ hybridization and whole-cell patch-clamp technology. The therapeutic efficacy of circGRIN2B in treating neuropathic pain was confirmed by assessing the pain threshold in a chronic constrictive injury (CCI) model. The interaction between circGRIN2B and NF-κB was examined through RNA pulldown, RIP, and mass spectrometry assays. CircGRIN2B knockdown significantly affected the action potential discharge frequency and the sodium-dependent potassium current flux (SLICK) in DRG neurons. Furthermore, knockdown of circGRIN2B dramatically reduced the SLICK channel protein and mRNA expression in vivo and in vitro. Our research confirmed the interaction between circGRIN2B and NF-κB. These findings demonstrated that circGRIN2B promotes the transcription of the SLICK gene by binding to NF-κB. In CCI rat models, the overexpression of circGRIN2B has been shown to hinder the progression of neuropathic pain, particularly by reducing mechanical and thermal hyperalgesia. Additionally, this upregulation significantly diminished the levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α in the DRG. Upon reviewing these findings, it was determined that circGRIN2B may mitigate the onset of neuropathic pain by modulating the NF-κB/SLICK pathway.

The effect of COVID-19 on pain control in patients with a neurostimulator in situ- a retrospective study.

BACKGROUND: De-novo chronic neuropathic pain following COVID-19 is widely recognised. However, there are currently no published studies investigating the effect of SARS-CoV-2 infection on patients with pre-existing neuropathic pain who have required spinal cord stimulator (SCS) implantation. Here, the authors aimed to analyse outcomes in their institution's patients who had spinal cord stimulator (SCS) implantation or revision procedures to the system over a 5-year period. Specifically, the short-term and long-term outcomes of patients who contracted COVID-19 during the follow-up period were compared to the control group of patients who did not. METHOD: Patients included in this study had spinal cord stimulator implantation (de-novo and revision procedures) between 1 January 2017 and 31 January 2022, for neuropathic pain of any aetiology. Patients deemed eligible for the study were invited to participate in a telephone survey through which clinical outcome data were collected. Pain scores were assessed with a modified form of the Brief Pain Inventory (BPI). RESULTS: Of 91 patients, 48 (52.7%) had contracted COVID-19 by the time of the survey. Patients who contracted COVID-19 had significantly worse BPI scores in the 'Least pain' domain following their infection and at time of the survey, when compared to their score 6 months after the operation. 22.9% (n = 11) of the patients who contracted COVID-19 experienced a change in their symptoms following their infection. Within this sub-group, there was a statistically significant deterioration in BPI scores in 10/11 domains following their infection and in 2/11 domains at time of the survey. Worsening severity of COVID-19 symptoms was not associated with worse BPI scores. CONCLUSIONS: Infection with SARS-CoV-2, in a significant proportion of patients with an SCS in situ, causes at least a transient deterioration in pain control. Further prospective multicentre studies are indicated to establish the prevalence of this phenomenon.

Use of a Sheath and Stylet for a Difficult Dorsal Root Ganglion Stimulation Lead Extraction: A Case Report.

Dorsal root ganglion stimulation (DRG-S) is a relatively new neuromodulation technique that has shown promising results in the treatment of chronic pain conditions. We present a case of a difficult lead extraction during the explantation of a DRG-S device. The lead was unable to be removed despite multiple attempts until a sheath and stylet were used to facilitate extraction. As DRG-S utilization becomes more widespread, DRG-S device explantation will inevitably become more common. The technique described in this report may be beneficial in certain cases of difficult DRG-S lead extraction.

Insular cortex stimulation alleviates neuropathic pain through changes in the expression of collapsin response mediator protein 2 involved in synaptic plasticity.

In recent studies, brain stimulation has shown promising potential to alleviate chronic pain. Although studies have shown that stimulation of pain-related brain regions can induce pain-relieving effects, few studies have elucidated the mechanisms of brain stimulation in the insular cortex (IC). The present study was conducted to explore the changes in characteristic molecules involved in pain modulation mechanisms and to identify the changes in synaptic plasticity after IC stimulation (ICS). Following ICS, pain-relieving behaviors and changes in proteomics were explored. Neuronal activity in the IC after ICS was observed by optical imaging. Western blotting was used to validate the proteomics data and identify the changes in the expression of glutamatergic receptors associated with synaptic plasticity. Experimental results showed that ICS effectively relieved mechanical allodynia, and proteomics identified specific changes in collapsin response mediator protein 2 (CRMP2). Neuronal activity in the neuropathic rats was significantly decreased after ICS. Neuropathic rats showed increased expression levels of phosphorylated CRMP2, alpha amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR), and N-methyl-d-aspartate receptor (NMDAR) subunit 2B (NR2B), which were inhibited by ICS. These results indicate that ICS regulates the synaptic plasticity of ICS through pCRMP2, together with AMPAR and NR2B, to induce pain relief.

Peripheral neuropathic pain: supporting patients with self-management.

Peripheral neuropathic pain is a complex condition that can adversely affect people's quality of life. Alongside pharmacological interventions, nurses can support patients to self-manage their pain using non-pharmacological interventions such as lifestyle changes and exercise. To do this effectively, nurses should be able to recognise the signs and symptoms of peripheral neuropathic pain and be able to educate patients on appropriate self-management approaches. It is important that nurses provide education, advice and information in a way that patients can understand and check this understanding. This article provides an overview of how nurses can support patients to self-manage peripheral neuropathic pain by using various non-pharmacological interventions.

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.

High-Frequency Spinal Stimulation Suppresses Microglial Kaiso-P2X7 Receptor Axis-Induced Inflammation to Alleviate Neuropathic Pain in Rats.

OBJECTIVE: Neuropathic pain poses a persistent challenge in clinical management. Neuromodulation has emerged as a last-resort therapy. Conventional spinal cord stimulation (Con SCS) often causes abnormal sensations and provides short analgesia, whereas high-frequency spinal cord stimulation (HF SCS) is a newer therapy that effectively alleviates pain without paresthesia. However, the modes of action of 10kHz HF SCS (HF10 SCS) in pain relief remain unclear. To bridge this knowledge gap, we employed preclinical models that mimic certain features of clinical SCS to explore the underlying mechanisms of HF10 SCS. Addressing these issues would provide the scientific basis for improving and evaluating the effectiveness, reliability, and practicality of different frequency SCS in clinical settings. METHODS: We established a preclinical SCS model to examine its effects in a neuropathic pain rat model. We conducted bulk and single-cell RNA sequencing in the spinal dorsal horn (SDH) to examine cellular and molecular changes under different treatments. We employed genetic manipulations through intrathecal injection of a lentiviral system to explore the SCS-mediated signaling axis in pain. Various behavioral tests were performed to evaluate pain conditions under different treatments. RESULTS: We found that HF10 SCS significantly reduces immune responses in the SDH by inactivating the Kaiso-P2X7R pathological axis in microglia, promoting long-lasting pain relief. Targeting Kaiso-P2X7R in microglia dramatically improved efficacy of Con SCS treatment, leading to reduced neuroinflammation and long-lasting pain relief. INTERPRETATION: HF10 SCS could improve the immunopathologic state in the SDH, extending its benefits beyond symptom relief. Targeting the Kaiso-P2X7R axis may enhance Con SCS therapy and offer a new strategy for pain management. ANN NEUROL 2024;95:966-983.

Ultrahigh frequency transcutaneous electrical nerve stimulation for neuropathic pain alleviation and neuromodulation.

A challenging complication in patients with peripheral compressive neuropathy is neuropathic pain. Excessive neuroinflammation at the injury site worsens neuropathic pain and impairs function. Currently, non-invasive modulation techniques like transcutaneous electrical nerve stimulation (TENS) have shown therapeutic promise with positive results. However, the underlying regulatory molecular mechanism for pain relief remains complex and unexplored. This study aimed to validate the therapeutic effect of ultrahigh frequency (UHF)-TENS in chronic constriction injury of the rat sciatic nerve. Alleviation of mechanical allodynia was achieved through the application of UHF-TENS, lasting for 3 days after one session of therapy and 4 days after two sessions, without causing additional damage to the myelinated axon structure. The entire tissue collection schedule was divided into four time points: nerve exposure surgery, 7 days after nerve ligation, and 1 and 5 days after one session of UHF therapy. Significant reductions in pain-related neuropeptides, MEK, c-Myc, c-FOS, COX2, and substance P, were observed in the injured DRG neurons after UHF therapy. RNA sequencing of differential gene expression in sensory neurons revealed significant downregulation in Cables, Pik3r1, Vps4b, Tlr7, and Ezh2 after UHF therapy, while upregulation was observed in Nfkbie and Cln3. UHF-TENS effectively and safely relieved neuropathic pain without causing further nerve damage. The decreased production of pain-related neuropeptides within the DRG provided the therapeutic benefit. Possible molecular mechanisms behind UHF-TENS may result from the modulation of the NF-κB complex, toll-like receptor-7, and phosphoinositide 3-kinase/Akt signaling pathways. These results suggest the neuromodulatory effects of UHF-TENS in rat sciatic nerve chronic constriction injury, including alleviation of neuropathic pain, amelioration of pain-related neuropeptides, and regulation of neuroinflammatory gene expression. In combination with the regulation of related neuroinflammatory genes, UHF-TENS could become a new modality for enhancing the treatment of neuropathic pain in the future.

Effects of swimming exercise on neuropathic pain in a rat model: role of glutamate.

OBJECTIVE: The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it. METHODS: In the present study 104 male Wistar rats weighing 180-220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography. RESULTS: Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it. IN CONCLUSION: The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission.

Cognitive, behavioral, and psychological phenotypes in small fiber neuropathy: A case-control study.

OBJECTIVE: Small fiber neuropathy (SFN) is a well-defined chronic painful condition causing severe individual and societal burden. While mood disorders have been described, cognitive and behavioral profiles of SFN patients has not been investigated. METHODS: Thirty-four painful SFN patients underwent comprehensive cognitive, behavioral, psychological, quality of life (QoL), and personality assessment using validated questionnaires. As control samples, we enrolled 36 patients with painful peripheral neuropathy (PPN) of mixed etiology and 30 healthy controls (HC). Clinical measures of neuropathic pain, duration, frequency, and intensity of pain at the time of assessment were recorded. Between-group and correlation analyses were performed and corrected for multiple comparisons. RESULTS: No differences in clinical measures were found between SFN and PPN, and all groups had similar cognitive profiles. SFN patients showed higher levels of anxiety and alexithymia (p < .005) compared to PPN and HC, considering also pain intensity. Maladaptive coping strategies characterized both patient groups, but only SFN revealed higher levels of acceptance of pain (p < .05). Pain intensity and neuropathic symptoms were associated with mood, low QoL and catastrophism (p < .001), particularly, the higher the perceived pain intensity, the higher the use of maladaptive coping strategies (p < .001). The personality assessment revealed significant feelings of worthlessness and somatization traits both in SFN and PPN (p < .002 vs HC). DISCUSSIONS: our results suggest that SFN patients had a normal-like cognitive profile, while their behavioral profile is characterized by mood disorders, alexithymia, maladaptive coping strategies, and poor QoL, as other chronic pain conditions, possibly related to pain intensity. Personality assessment suggests that somatization and feelings of worthlessness, which may worsen the neuropsychological profile, deserve clinical attention when considering patients' therapeutic approaches. At the same time, the high level of acceptance of pain is promising for therapeutic approaches based on psychological support.

High-voltage pulsed radiofrequency improves ultrastructure of DRG and enhances spinal microglial autophagy to ameliorate neuropathic pain induced by SNI.

Neuropathic pain (NeP) is intractable for which many therapies are ineffective. High-voltage pulsed radiofrequency (HVPRF) on dorsal root ganglion (DRG) is considered an effective treatment for NeP. The aim of this study is to explore the therapeutic voltage for the optimal efficacy of PRF and the underlying mechanisms. The radiofrequency electrode was placed close to the L5 DRG of rats with spared nerve injury (SNI) and emitted current by the corresponding voltage in different groups. Four different voltages (45 V, 65 V, 85 V, and 100 V) of PRF on DRG significantly alleviated the SNI-induced NeP, reduced the levels of activating transcription factor 3 (ATF3) in DRG, improved the ultrastructure of DRG, and promoted autophagy in spinal microglia to varying degrees and partially reversed the increased expression of TNF-α and the reduced expression of IL-10 in spinal cord dorsal horn (SCDH). The beneficial effect of 85V-PRF was superior to those of other three PRF treatments. The underlying mechanisms may be related to repairing the DRG damage and improving the DRG ultrastructure while regulating spinal microglial autophagy and thereby alleviating neuroinflammation.

Impact of inflammation and Treg cell regulation on neuropathic pain in spinal cord injury: mechanisms and therapeutic prospects.

Spinal cord injury is a severe neurological trauma that can frequently lead to neuropathic pain. During the initial stages following spinal cord injury, inflammation plays a critical role; however, excessive inflammation can exacerbate pain. Regulatory T cells (Treg cells) have a crucial function in regulating inflammation and alleviating neuropathic pain. Treg cells release suppressor cytokines and modulate the function of other immune cells to suppress the inflammatory response. Simultaneously, inflammation impedes Treg cell activity, further intensifying neuropathic pain. Therefore, suppressing the inflammatory response while enhancing Treg cell regulatory function may provide novel therapeutic avenues for treating neuropathic pain resulting from spinal cord injury. This review comprehensively describes the mechanisms underlying the inflammatory response and Treg cell regulation subsequent to spinal cord injury, with a specific focus on exploring the potential mechanisms through which Treg cells regulate neuropathic pain following spinal cord injury. The insights gained from this review aim to provide new concepts and a rationale for the therapeutic prospects and direction of cell therapy in spinal cord injury-related conditions.