Painful Neuropathy Research Articles

Retraction: Potamogeton perfoliatus L. extract attenuates neuroinflammation and neuropathic pain in sciatic nerve chronic constriction injury-induced peripheral neuropathy in rats

Retraction: Potamogeton perfoliatus L. extract attenuates neuroinflammation and neuropathic pain in sciatic nerve chronic constriction injury-induced peripheral neuropathy in rats

Paclitaxel alters the microvascular network in the central and peripheral nervous system of rats with chemotherapy-induced painful peripheral neuropathy.

Chemotherapy-induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose-limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN. We evaluated the severity of CIPN with neurophysiological, behavioural and neuropathological analysis together with the microvascular network in central and peripheral nervous systems of rats in order to correlate the features of the CIPN and the vascular abnormalities. The vascular network was quantitatively evaluated through synchrotron radiation-based X-ray phase-contrast micro-tomography imaging, measuring four specific parameters: vascular density, vessel diameter, vessel tortuosity and branching. Rats exposed to paclitaxel and affected by a severe painful sensory axonopathy showed an increased vascular density (putative sprouting angiogenesis) in the crucial districts of the central (somatosensory cortex and lumbar spinal cord) and peripheral nervous system (lumbar dorsal root ganglia). In addition, the complexity of the vascular network and the size of neo-formed vessels were significantly decreased in specific regions. On the other hand, less significant changes were observed in rats exposed to cisplatin, affected by a painless peripheral neuropathy, suggesting a specific involvement of neo-angiogenesis in the development of severe neurotoxicity and neuropathic pain. These new ground-breaking results can shed light on new pathogenetic mechanisms and potential novel therapeutic approaches for painful-CIPN.

Exploring the potential therapeutic benefits of 7-methoxy coumarin for neuropathy pain: an in vivo, in vitro, and in silico approach.

7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods. Vincristine (0.1mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitrostudies on phospholipase inhibition by 7-MC showed an IC50 of 27.08µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin. The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.

Observing nociceptive detection thresholds and evoked potentials in diabetic patients with and without painful neuropathy

Aim: Diabetic polyneuropathy is the most described complication in patients with diabetes mellitus. A significant percentage of these patients experience disabling neuropathic pain (painful diabetic polyneuropathy). Small nerve fibers are primarily responsible for peripheral nociception, but objectively assessing its function is challenging. The primary objective of this study was to explore the task execution and outcomes of intra-epidermal electrical stimulation technique that combines nociceptive detection thresholds (NDT) and evoked potentials (EPs) in patients with diabetes. We compared the results of diabetic patients, both with and without painful diabetic polyneuropathy, with those of healthy controls to explore potential clinically relevant information. Methods: The NDT-EP method was applied to 38 patients with diabetes (18 with and 20 without chronic painful neuropathy) and 38 age- and sex-matched healthy controls. Individual mean NDTs, psychometric slopes, EP amplitudes, and the effect of the stimuli on EP amplitudes were analyzed and compared between groups using linear regression. Results: The findings revealed significantly lower detection rates, higher NDTs, and lower psychometric slopes in patients with painful diabetic polyneuropathy than in healthy controls. Both patient groups significantly exhibited lower mean EP amplitudes than healthy controls, which were not linked to pulse amplitudes but influenced by stimulus detection. Conclusions: This study showed altered NDT-EP outcomes in patients with painful diabetic polyneuropathy. Whereas the task execution, NDTs, and psychometric slopes may provide valuable insights into small fiber dysfunction, pulse amplitudes seemed not differently encoded in neurophysiological responses to intra-epidermal electrical stimulation near the detection threshold compared to controls. Future studies should investigate whether the altered NDT-EP outcomes could quantify small fiber dysfunction in patients with diabetes mellitus. We recommend further exploration of NDT-EP measures in other patient groups with nociceptive dysfunction.

Electroacupuncture with different frequencies for paclitaxel-induced peripheral neuropathy: a randomized controlled trial

To observe the clinical efficacy of electroacupuncture (EA) at frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz for chemotherapy-induced peripheral neuropathy (CIPN). One hundred and sixty female breast cancer patients with CIPN induced by paclitaxel were randomly divided into a 2 Hz EA group (40 cases, 1 case dropped out), a 100 Hz EA group (40 cases, 2 cases dropped out), a 2 Hz/100 Hz EA group (40 cases, 3 cases dropped out), and a medication group (40 cases, 2 cases dropped out). The three EA groups received acupuncture at bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Zusanli (ST 36), and Yanglingquan (GB 34). Electrodes of the HANS-200E acupoint nerve stimulator were connected to the same side Hegu (LI 4) and Waiguan (TE 5), and Zusanli (ST 36) and Sanyinjiao (SP 6), with EA stimulation frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz, respectively. Each session lasted 30 min, once every other day, three times a week. The medication group received oral mecobalamin tablets, 0.5 mg per dose, three times a day. All groups were treated for four weeks. The functional assessment of cancer therapy/gynaecologic oncology group-neurotoxicity (FACT/GOG-Ntx), peripheral neurotoxicity grading based on the National Cancer Institute-common terminology criteria for adverse events Version 5.0 (NCI-CTCAE V5.0), and peripheral neuropathy pain visual analogue scale (VAS) scores were observed before and after treatment, and at follow-up after 4 weeks of treatment completion, and clinical efficacy was evaluated after theatment. Compared before treatment, FACT/GOG-Ntx scores in all groups were decreased after treatment and during follow-up (P<0.01). The score reduction between before and after treatment in the three EA groups was greater than the medication group (P<0.01, P<0.05), with the 2 Hz and 2 Hz/100 Hz EA groups showing a greater reduction than the 100 Hz EA group (P<0.05). The reduction of FACT/GOG-Ntx score between before treatment and follow-up in the 2 Hz and 2 Hz/100 Hz EA groups was greater than the medication group (P<0.01). Peripheral neurotoxicity grading in the three EA groups were improved after treatment (P<0.01). Compared before treatment, the peripheral neurotoxicity grading in the 2 Hz and 2 Hz/100 Hz EA groups was improved at follow-up (P<0.01, P<0.05). The VAS scores for peripheral neuropathy pain in the three EA groups were decreased after treatment (P<0.01, P<0.05). At follow-up, VAS scores in the 2 Hz, 2 Hz/100 Hz, and medication groups were decreased (P<0.01, P<0.05), with a greater reduction in the 2 Hz/100 Hz EA group than the medication group after treatment and follow-up (P<0.01, P<0.05). The overall effective rates for the 2 Hz, 100 Hz, 2 Hz/100 Hz, and medication groups were 79.5% (31/39), 68.4% (26/38), 81.1% (30/37), and 47.4% (18/38), respectively, with the 2 Hz and 2 Hz/100 Hz groups showing higher effective rates than the medication group (P<0.05). EA is effective in treating paclitaxel-induced CIPN. While there is no overall difference in efficacy among the different frequencies, 2 Hz and 2 Hz/100 Hz EA showing potential advantages. For patients with concurrent peripheral neuropathy pain, 2 Hz/100 Hz electroacupuncture is recommended.

Effect of Contrast Bath on Level of Neuropathic Pain among Patients with Type 2 Diabetes Mellitus

Diabetic neuropathy is a chronic sequela of DM and contrast bath is a non-pharmacological treatment modality which can reduce neuropathic pain among them. The present study was intended to assess the effect of contrast bath on level of neuropathic pain among patients with T2DM. The main objectives of the study were to assess the level of neuropathic pain among patients with T2DM, assess the effect of contrast bath on level of neuropathic pain and to determine the association between the neuropathic pain and socio demographic and clinical variables. The research approach was quantitative and the design adopted was quasi experimental. Sample consists of 60 patients with T2DM having neuropathic pain attending OPDs of Ananthapuri hospital selected by consecutive sampling technique. The conceptual framework adopted for the study was Wiedenbach’s Prescriptive theory. A structured interview schedule was used to collect socio demographic and clinical variables and Galer Neuropathy Pain Scale for assessing the neuropathic pain. Pre-test was done for both groups. After explanation and ensuring safety contrast bath was administered to experimental group for 20 minutes. Post-test was done by using the same tool for both experimental and control group. Mean, frequency, percentage were used to describe the data. Independent t test was used to assess the effect of contrast bath and association of level of neuropathic pain with socio demographic and clinical variables. The results revealed statistically significant (p&lt;0.01) difference in the mean score of neuropathic pain in the experimental and control group after intervention. There was no significant association between level of neuropathic pain and socio demographic and clinical variables. The study infers that contrast bath is a simple non pharmacological home-based cost-effective intervention which can improve the daily functional abilities of patients with DM and thereby enhancing their quality of life.

A review on food Safety challenges in Chilli (Capsicum annuum L) and mitigation measures

Capsicum annuum L., often known as hot pepper or chilly pepper, is a vital vegetable crop and spice in the Solanaceae family. Since ancient times, people have used chilies as a flavoring, ingredient in food, and family medicine for a variety of illnesses, such as high blood pressure, arthritis, skin problems, and high cholesterol. They have also been used as a carminative, snack, stomachic, and refreshment, as well as a means of relieving pain in neuropathy and as a counterirritant in the treatment of lumbago and stiffness. Its organic design is to stop herbivorous creatures, parasites, and different microorganisms. The expression "capsicum" comes from the Greek word "kapsimo," and that signifies "to chomp". Dried chilly is susceptible to contaminants such as mould dirt and pesticides that must be removed to maintain the safety and quality of products.

The single-cell transcriptomic atlas iPain identifies senescence of nociceptors as a therapeutical target for chronic pain treatment

Chronic pain remains a significant medical challenge with complex underlying mechanisms, and an urgent need for new treatments. Our research built and utilized the iPain single-cell atlas to study chronic pain progression in dorsal root and trigeminal ganglia. We discovered that senescence of a small subset of pain-sensing neurons may be a driver of chronic pain. This mechanism was observed in animal models after nerve injury and in human patients diagnosed with chronic pain or diabetic painful neuropathy. Notably, treatment with senolytics, drugs that remove senescent cells, reversed pain symptoms in mice post-injury. These findings highlight the role of cellular senescence in chronic pain development, demonstrate the therapeutic potential of senolytic treatments, and underscore the value of the iPain atlas for future pain research.

NaV1.8/NaV1.9 double deletion mildly affects acute pain responses in mice.

The 2 tetrodotoxin-resistant (TTXr) voltage-gated sodium channel subtypes NaV1.8 and NaV1.9 are important for peripheral pain signaling. As determinants of sensory neuron excitability, they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and the release of neurotransmitters from sensory neuron terminals. NaV1.8 and NaV1.9, which are encoded by SCN10A and SCN11A, respectively, are predominantly expressed in pain-sensitive (nociceptive) neurons localized in the dorsal root ganglia (DRG) along the spinal cord and in the trigeminal ganglia. Mutations in these genes cause various pain disorders in humans. Gain-of-function missense variants in SCN10A result in small fiber neuropathy, while distinct SCN11A mutations cause, i. a., congenital insensitivity to pain, episodic pain, painful neuropathy, and cold-induced pain. To determine the impact of loss-of-function of both channels, we generated NaV1.8/NaV1.9 double knockout (DKO) mice using clustered regularly interspaced short palindromic repeats/Cas-mediated gene editing to achieve simultaneous gene disruption. Successful knockout of both channels was verified by whole-cell recordings demonstrating the absence of NaV1.8- and NaV1.9-mediated Na+ currents in NaV1.8/NaV1.9 DKO DRG neurons. Global RNA sequencing identified significant deregulation of C-LTMR marker genes as well as of pain-modulating neuropeptides in NaV1.8/NaV1.9 DKO DRG neurons, which fits to the overall only moderately impaired acute pain behavior observed in DKO mice. Besides addressing the function of both sodium channels in pain perception, we further demonstrate that the null-background is a very valuable tool for investigations on the functional properties of individual human disease-causing variants in NaV1.8 or NaV1.9 in their native physiological environment.

ID: 330248 High Cervical Spinal Cord Stimulation for the Treatment of Chronic Postoperative Painful Trigeminal Neuropathy

ID: 330248 High Cervical Spinal Cord Stimulation for the Treatment of Chronic Postoperative Painful Trigeminal Neuropathy

ID: 316704 Spinal Cord Stimulation in the Treatment of Painful Length-dependent Peripheral Neuropathy: A Systematic Review

ID: 316704 Spinal Cord Stimulation in the Treatment of Painful Length-dependent Peripheral Neuropathy: A Systematic Review

Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy.

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.

Glycemic variability’s impact on painful diabetic peripheral neuropathy in type 2 diabetes patients

Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN.

Neurologic Clinical, Electrophysiologic, and Pathologic Characteristics of Primary vs Secondary Neurolymphomatosis.

Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups. This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020. Patient clinical characteristics, neurologic examination, imaging studies, EMG, and nerve biopsy data were collected, analyzed, and compared between PNL and SNL. A total of 58 patients were identified (34 PNL and 24 SNL). Time from neurologic symptom onset to diagnosis was longer in PNL at 18.5 months compared with 5.5 months in SNL (p = 0.01). Neurologic symptoms were similar in both patient groups and included primarily sensory loss (98%), severe pain (76%), and asymmetric weakness (76%). A wide spectrum of EMG-confirmed different neuropathy patterns were observed, but patients with SNL had increased numbers of mononeuropathies (n = 8) compared with PNL (n = 1, p = 0.01). MRI studies detected NL more frequently (86%) compared with fluorodeoxyglucose (FDG)-PET CT imaging studies (60%) (p = 0.007). Nerve biopsies revealed B-cell lymphoma (PNL n = 32, SNL n = 22), followed by T-cell lymphoma (PNL n = 2, SNL n = 2), with increased demyelination in both groups and increased axonal degeneration (p = 0.01) and multifocal myelinated fiber loss (p = 0.04) significant in SNL vs PNL. Identifying SNL resulted in patient treatment modifications but a worse prognosis compared with PNL (p = 0.025). While PNL and SNL are both primarily painful and asymmetric neuropathies with axonal and demyelinating features on EMG and nerve biopsy, SNL presents somewhat differently than PNL with fulminant, asymmetric often mononeuropathies better detected on MRI than FDG-PET/CT. The focal pattern of SNL is likely a result of residual cancer cells that evaded initial chemotherapy, which does not cross the blood-nerve barrier, and these cells can later recur and result in fulminant disease. Although still resulting in a poorer prognosis, identifying SNL is important because this changed treatment and management in every SNL case.

A retrospective study to assess the complications associated with surgical management of distal radius fracture by ligamentotaxis

Background: Fractures of the distal radius are the most common upper limb fractures encountered by orthopedic surgeons. It constitutes about 75% of all the forearm fractures. There is steady increase in this type of fracture in all age groups but is the highest in children and elderly. There are multiple modalities of treatment available for distal end radius fractures, among which ligamentotaxis is one of the modalities, where the ligaments, retinaculum, tendons and periosteum that envelope the fracture serves as barrier during open reduction, helps achieve the reduction of the fracture. The objective is to study the most common complication associated with distal radius fractures treated by ligamentotaxis in this institution. Methods: This hospital based retrospective study was conducted at MVJMC and RH after receiving ethical clearance from the institutional ethical committee. The study population contained 50 patients that met the inclusion criteria over a period of 4 years from March 2019 to March 2024.The administrative health data was collected from OPD and OT registers, and the collected data was entered in Microsoft excel and results were calculated and tabulated at the end of the period. All the patients with distal end radius fractures treated by ligamentotaxis over a period of 4 years were included Results: According to the study distal end radius fracture was more prevalent among males than females and the highest percentage with 30% was seen among the age group of 31-40 years. The most common complication encountered was neuropathy and residual wrist pain which accounted for 14%. Conclusions: The study concludes that most of the fractures and its complications are note among the active age group. The study helps understand the complications and find strategies to reduce the complication percentage.

Mu-Opioid Receptor (MOR) Dependence of Pain in Chemotherapy-Induced Peripheral Neuropathy.

We recently demonstrated that transient attenuation of Toll-like receptor 4 (TLR4) in dorsal root ganglion (DRG) neurons, can both prevent and reverse pain associated with chemotherapy-induced peripheral neuropathy (CIPN), a severe side effect of cancer chemotherapy, for which treatment options are limited. Given the reduced efficacy of opioid analgesics to treat neuropathic, compared to inflammatory, pain, the crosstalk between nociceptor TLR4 and mu-opioid receptors (MOR), and that MOR and TLR4 agonists induce hyperalgesic priming (priming), which also occurs in CIPN, we determined, using male rats, whether: i ) antisense knockdown of nociceptor MOR attenuates CIPN, ii ) and attenuates the priming associated with CIPN, and iii ) CIPN also produces opioid-induced hyperalgesia (OIH). We found that intrathecal MOR antisense prevents and reverses hyperalgesia induced by oxaliplatin and paclitaxel, two common clinical chemotherapy agents. Oxaliplatin induced-priming was also markedly attenuated by MOR antisense. Additionally, intradermal morphine, at a dose that does not affect nociceptive threshold in controls, exacerbates mechanical hyperalgesia (OIH) in rats with CIPN, suggesting the presence of OIH. This OIH associated with CIPN is inhibited by interventions that reverse Type II priming (the combination of an inhibitor of Src and mitogen-activated protein kinase (MAPK)), a MOR antagonist, as well as a TLR4 antagonist. Our findings support a role of nociceptor MOR in oxaliplatin-induced pain and priming. We propose that priming and OIH are central to the symptom burden in CIPN, contributing to its chronicity and the limited efficacy of opioid analgesics to treat neuropathic pain.Significance Statement It remains unknown why opioid analgesics are less effective against neuropathic pain, including that induced by cancer chemotherapy. Here we demonstrate a crucial role of nociceptor mu-opioid receptors (MOR) in chemotherapy-induced peripheral neuropathy (CIPN) pain and hyperalgesic priming (priming), the latter a mechanism involved in the transition from acute to chronic pain. In addition to neuropathic pain and priming, opioid-induced hyperalgesia (OIH) also develops in chemotherapy-treated rats, which is reversed by inhibitors of second messengers that also reverse Type II priming, as well as by MOR and TLR4 antagonists. Taken together our results support the suggestion that priming and OIH contribute to CIPN and its limited responsiveness to opioid analgesics.

Yiqi Huoxue Tongluo formula-containing serum attenuates high glucose-induced injury in microglia via MAPK pathways: Network pharmacology-based analysis and biological validation

IntroductionThe Yiqi Huoxue Tongluo formula (YQHX), containing Astragalus mongholicus Bunge, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa Libosch., Pueraria lobata (Willd.) Ohwi, Corydalis yanhusuo W.T.Wang, Spatholobus suberectus Dunn, Clematis chinensis Osbeck, is a proprietary formula of the First Affiliated Hospital of Anhui University of Chinese Medicine, and can attenuate diabetic neuropathy pain (DNP). This study aimed to explore the mechanisms underlying YQHX-mediated DNP alleviation. Additionally, the effects of YQHX on BV2 microglia injured by high glucose via the mitogen-activated protein kinase (MAPK) signaling pathways were investigated. MethodsLiquid chromatography tandem mass spectroscopy (LC-MS/MS) was performed to identify the chemical compounds in YQHX. The potential mechanism of YQHX for treating DNP was explored through network pharmacology analysis. The established glucose-induced BV2 cell injury model was treated with varying concentrations of YQHX-containing serum. The effects of YQHX-containing serum and MAPK pathway inhibitors on microglial cells were assessed by Cell Counting Kit-8 and enzyme-linked immunosorbent assays. The messenger RNA (mRNA) and protein levels of microglial marker OX42 were measured. Additionally, phosphorylated-p38, -c-Jun-terminal kinase, and -extracellular signal-regulated kinase and downstream nuclear factor-κB/p65 and phosphorylated-activating transcription factor 2 (ATF2) proteins were detected by western blotting. ResultsIn total, 503 chemical components were identified in YQHX by LC-MS/MS analysis. Network pharmacology results showed 203 active ingredients and 363 overlapping targets, respectively, as potential therapeutic candidates for YQHX-mediated DNP treatment. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded a total of 105 signal pathways. Notably, YQHX considerably improved the cell viability of BV2 cells (P < 0.01), remarkably reduced the production of proinflammatory factors (P < 0.01), significantly increased the production of anti-inflammatory factors (P < 0.01), and markedly inhibited the mRNA and protein levels of OX42 (P < 0.01). Furthermore, YQHX treatment inhibited MAPK activation and ATF2 expression. ConclusionsYQHX may protect against high-glucose-induced BV2 microglial cell injury by inhibiting the activation of MAPKs and downstream ATF2, thus, reducing microglial activation and proinflammatory cytokine release. These results provide a foundational theoretical basis for exploring the further mechanism of YQHX in treating DNP, and they provide a novel target for the application of traditional Chinese medicine.

Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK

ObjectiveThe chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS...

ART26.12, a novel fatty acid-binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models.

Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy. In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity. ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment. Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy. This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.

Nageotte nodules in human DRG reveal neurodegeneration in painful diabetic neuropathy.

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invaded Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings solve a 100-year mystery of the nature of Nageotte nodules linking these pathological structures to pain and sensory loss in DPN.