Occurrence Of Neuropathic Pain Research Articles

The correlation between vitamin D and the occurrence of peripheral neuropathy induced by paclitaxel chemotherapy.

Paclitaxel, a widely used chemotherapeutic agent for various cancers, induces peripheral neuropathy (PIPN) in approximately 80% of patients, severely affecting their quality of life. The role of vitamin D in pain perception has gained attention, but its correlation with PIPN remains unclear. This study included 129 cancer patients who received adjuvant paclitaxel chemotherapy from January to June 2023. Neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) questionnaire, and serum levels of vitamin D and glutathione (GSH) were measured to explore the correlation between vitamin D levels and neuropathic pain induced by paclitaxel chemotherapy. The results showed a negative correlation between vitamin D deficiency and the occurrence of neuropathic pain (Spearman correlation coefficient of -0.324, P < 0.001). The receiver operating characteristic (ROC) curve analysis revealed that the area under the vitamin D curve for neuropathic pain was 0.681. Furthermore, after paclitaxel chemotherapy, there was a significant decrease in GSH levels in the serum of patients, with a more pronounced decline in the vitamin D-deficient group. The findings of this study indicate that higher levels of vitamin D are negatively associated with the occurrence of paclitaxel-induced neuropathic pain, suggesting that vitamin D might protect against oxidative stress. This discovery is significant for clinical treatment as it may help physicians better understand the mechanisms of pain during paclitaxel therapy and provide new strategies for the prevention and treatment of such pain. It also suggests that modulating vitamin D levels could reduce the neurotoxicity of paclitaxel, thereby improving patients' quality of life and treatment compliance.

Silencing of FTO inhibits oxidative stress to relieve neuropathic pain by m6A modification of GPR177.

Neuropathic pain (NP) is a challenging health condition owing to its complex nature and associated multiple etiologies. The occurrence of NP involves the abnormal activity of neurons mediated by oxidative stress (OS). Previous research has demonstrated that m6A methylation plays a role in the regulatory pathway of NP. This study aimed to investigate the specific molecular pathways through which m6A methylation modifiers alleviate NP. For this purpose, an NO rat model was developed via spared nerve injury (SNI), followed by quantifying the animal's pain assessment via paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The OS in SNI rats was evaluated by measuring reactive oxygen species, superoxide dismutase, and catalase (CAT) in spinal cord tissues. Moreover, quantitative-real-time polymerase chain reaction and western blot analysis were employed for detecting fat mass and obesity-associated (FTO) and GPR177 levels, while m6A levels of GPR117 were analyzed via MeRIP. The results indicated an enhanced OS with highly expressed FTO in spinal cord tissue samples, where knocking down Fto effectively relieved NP and OS in SNI rats. Mechanistic investigations revealed that Fto-mediated reduction of Grp177 m6A modification was involved in the WNT5a/TRPV1 axis-mediated OS remission of NP. Moreover, in vitro experiment results indicated that YTHDF2 was an important m6A methylated reading protein for this process. Fto silencing leads to increased m6A methylation of Grp177 through a YTHDF2-dependent mechanism, resulting in decreased Grp177 stability and ultimately reducing NP in rats by OS suppression.

Postoperative Dexmedetomidine Infusion and Chronic Postsurgical Pain in Thoracoscopic Pulmonary Nodule Surgery: A Retrospective Study with Propensity-Score-Matched Analysis.

Patients frequently suffer from debilitating chronic postsurgical pain (CPSP) subsequent to thoracoscopic surgery. The impact of postoperative dexmedetomidine infusion on CPSP remains elusive. This study aimed to scrutinize the effect of dexmedetomidine on both 1-year incidence of CPSP and the quality of recovery after thoracoscopic pulmonary nodule surgery. This retrospective analysis encompassed clinical and follow-up data from 1148 patients undergoing thoracoscopic pulmonary nodule surgery at our institution between September 2021 and August 2022. Depending on whether dexmedetomidine was infused intravenously or not on the first night after surgery, patients were stratified into the dexmedetomidine group or the control group, with propensity score matching applied to harmonize baseline characteristics. Comparative analysis sought to delineate distinctions of CPSP and recovery quality 1year after surgery. Following propensity score matching, a cohort of 258 patients in each group underwent analysis. Comparisonsafter matching revealed no statistically significant disparities in 1-year CPSP incidence [76/258 (29.5%) versus 78/258 (30.2%), P = 0.847], moderate-to-severe pain occurrence [17/76 (22.4%) versus 22/78 (28.2%), P = 0.405], neuropathic painoccurrence [11/76 (14.5%) versus 11/78 (14.1%), P = 0.948], and postoperative recovery quality assessed by 12-Item Short Form Health Survey (SF-12) score (113.1 [107.2, 116.0] versus 113.0 [107.4, 116.0], P = 0.328). Multivariate logistic regression analysis encompassing the entire cohort identified being female [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.59-2.79, P < 0.001) and postoperative rescue analgesia (OR 1.47, 95% CI 1.09-1.96, P = 0.010) as risk factors for CPSP, while intraoperative fentanyl dosage (OR 0.92, 95% CI 0.87-0.98, P = 0.006) emerged as a protective factor. The prolonged administration of dexmedetomidine did not yield discernible amelioration in either 1-year CPSP or the recovery quality after thoracoscopic surgery. Noteworthy risk factors for CPSP encompassed female sex, postoperative rescue analgesia, and diminished fentanyl dosage intraoperatively.

LPAR6 Participates in Neuropathic Pain by Mediating Astrocyte Cells via ROCK2/NF-κB Signal Pathway.

Neuropathic pain (NPP) is a common type of chronic pain. Glial cells, including astrocytes (AS), are believed to play an important role in the progression of NPP. AS cells can be divided into various types based on their expression profiles, among which A1 and A2 types have clear functions. A1-type AS cells are neurotoxic, while A2-type AS cells exert neuroprotective functions. Some types of lysophosphatidic acid receptors (LPAR) have been shown to play a role in NPP. However, it remains unclear how AS cells and LPAR6 affect the occurrence and progression of NPP. In this study, we established a mouse model of chronic constriction injury (CCI) to simulate NPP. It was found that the expression of LPAR6 in AS cells of the spinal dorsal horn was increased in the CCI model, and the thresholds of mechanical and thermal pain were elevated after knocking out LPAR6, indicating that LPAR6 and AS cells participated in the occurrence of NPP. The experiment involved culturing primary AS cells and knocking down LPAR6 by Lentivirus. The results showed that the NF-κB signal pathway was activated and the number of A1-type AS cells increased in the CCI model. However, LPAR6 knockdown inhibited the NF-κB signal pathway and A1-type AS cells. The results of the mRNA sequencing and immunoprecipitation test indicate an interaction between LPAR6 and ROCK2. Inhibiting ROCK2 by Y-27632 increased mechanical and thermal pain thresholds and alleviated NPP at the molecular level. The study presents evidence that LPAR6 activates the NF-κB pathway through ROCK2 and contributes to the progression of NPP by increasing A1-type AS and decreasing A2-type AS. This suggests that LPAR6 could be a potential therapeutic target for alleviating NPP. Clinical applications that are successful can offer new therapeutic options, enhance the quality of life for patients, and potentially uncover new mechanisms for pain modulation.

Neuroprotective Effect of Polyvalent Immunoglobulins on Mouse Models of Chemotherapy-Induced Peripheral Neuropathy.

The occurrence of neuropathic pain in chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting effect of many commonly-used anticancer agents. Polyvalent human immunoglobulins (hIg), used in the treatment of several peripheral neuropathies, may alleviate neuropathic pain. The aim of this project was to investigate the preventive effect of hIg in two mouse models of CIPN, induced by vincristine (VCR, 100 µg/kg/d) and oxaliplatin (OXP, 6 mg/kg/3d). Human Ig were administered one day before the first injection of chemotherapy. The onset of CIPN and effects of hIg were assessed via functional tests and morphological analyses of sensory nerves. To evaluate the effect of hIg on chemotherapy cytotoxicity, viability assays were performed using hIg (0 to 12 mg/mL) combined with anticancer agents on human cancer cell lines. The preventive treatment with hIg alleviated tactile hypersensitivity and nerve injuries induced by VCR. It also alleviated tactile/cold hypersensitivities and nerve injuries induced by OXP. Treatment with hIg did not affect the cytotoxicity of either chemotherapy. Furthermore, in combination with VCR, hIg potentiated chemo-induced cell death. In conclusion, hIg is a promising therapy to prevent the onset of CIPN and potentiate chemotherapy effect on cancer, reinforcing the interest in hIg in the management of CIPN.

Dock4 contributes to neuropathic pain by regulating spinal synaptic plasticity in mice.

Neuropathic pain (NP) conditions arising from injuries to the nervous system due to trauma, disease, or neurotoxins are chronic, severe, debilitating, and exceedingly difficult to treat. However, the mechanisms of NP are not yet clear. Here we explored the role of Dock4, an atypical Rac1 GEF, in the development of NP. Mechanical allodynia was assessed as paw withdrawal threshold by a dynamic plantar aesthesiometer. Immunofluorescence staining was conducted to investigate the expression and localization of Dock4, Rac1 and GluN2B. Quantitative analysis of Dock4, Rac1 and GluN2B were determined by qRT-PCR and Western blot assay. Spontaneous excitatory and inhibitory postsynaptic currents in spinal cord slices were examined using whole cell patch clam. Dendritic spine remodeling and synaptogenesis were detected in cultured dorsal spinal neurons. We found that SNL caused markedly mechanical allodynia accompanied by increase of Dock4, GTP-Rac1and GluN2B, which was prevented by knockdown of Dock4. Electrophysiological tests showed that SNL facilitated excitatory synaptic transmission, however, this was also inhibited by Dock RNAi-LV. Moreover, knockdown of Dock4 prevented dendritic growth and synaptogenesis. In summary, our data indicated that Dock4 facilitated excitatory synaptic transmission by promoting the expression of GluN2B at the synaptic site and synaptogenesis, leading to the occurrence of NP.

Relationship between Nontraumatic Shoulder Disorders and Neuropathic Pain: Retrospective Observational Analyses of Clinical Features and Background Factors.

Accurate identification of neuropathic pain is necessary for appropriate treatment; however, the relationship between nontraumatic shoulder disorders and neuropathic pain remains unknown. Therefore, this retrospective observational study aimed to investigate the relationship, features, background factors, and prevalence of neuropathic pain among patients with nontraumatic shoulder disorders. We evaluated 198 patients who visited our outpatient clinic, which specializes in shoulder disorders, from April 2015 to March 2016. The patients' age, sex, affected side, diagnosis, and pain duration were recorded, and the results of physical examination, including passive range of motion, impingement sign, and muscular strength assessments, were analyzed. The presence of neuropathic pain was assessed using the painDETECT questionnaire. Participants were divided into two groups according to the presence of neuropathic pain. Pain intensity was assessed using a visual analog scale, and the patient's mental status was assessed using the short-form McGill Pain Questionnaire and Hospital Anxiety and Depression Scale. The scores were compared between the groups. Neuropathic pain was observed in 7.6% of patients. The visual analog scale score for pain, short-form McGill Pain Questionnaire score, and Hospital Anxiety and Depression Scale score were significantly associated with the presence of neuropathic pain in the univariate analysis. Patient background factors and physical function were not associated with the presence of neuropathic pain. The prevalence of neuropathic pain in patients with frozen shoulder was 33.3%, which was significantly higher than that in patients with other shoulder disorders. The occurrence of neuropathic pain may aggravate pain in patients with nontraumatic shoulder disorders. Neuropathic pain was not a rare condition in patients with nontraumatic shoulder disorders, particularly in those with frozen shoulder. The coexistence of neuropathic pain cannot be determined from background factors or physical function. Accurate diagnosis of neuropathic pain is essential in patients with nontraumatic shoulder disorders.

Long non-coding RNA Snhg16 Lessens Ozone Curative Effect on Chronic Constriction Injury mice via microRNA-719/SCN1A axis.

We investigated the function and molecular mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (Snhg16) in modifying ozone treatment for neuropathic pain (NP) in a mouse model of chronic constriction injury (CCI). Pain-related behavioral responses were evaluated using paw withdrawal threshold (PWT), paw lifting number (PLN), and paw withdrawal latency (PWL) tests. Interleukin (IL)-1β, IL-10, IL-6, and tumor necrosis factor-alpha (TNF-α) were measured by ELISA and qRT-PCR to evaluate neuroinflammation. qRT-PCR was performed to detect expressions of Snhg16, microRNA (miR)-719, sodium voltage-gated channel alpha subunit 1 (SCN1A), and inflammatory factors. Bioinformatics, dual-luciferase reporter assay, and RNA pull-down verified the underlying molecular mechanisms. Snhg16 expression increased in CCI mice. Snhg16 overexpression retarded the curative effect of ozone and induced NP. miR-719 was sponged by Snhg16. SCN1A was a target of miR-719. Inhibition of miR-719 markedly reversed the effects of Snhg16 on pain-related behavioral responses and neuroinflammation. Upregulation of SCN1A partly abrogated the effects of elevated miR-719 levels on the occurrence of NP. The findings demonstrate that lncRNA Snhg16 promotes NP progression in CCI mice by binding to miR-719 to increase SCN1A expression. The Snhg16/miR-719/SCN1A axis may influence the curative effects of ozone therapy in treating NP.

Occurrence of neuropathic pain and its characteristics in patients with traumatic spinal cord injury

Objectives Assess the occurrence of neuropathic pain in spinal cord injured persons (SCIP) and define the relationship between neuropathic pain with demographic and clinical characteristics in SCIPs. Methods This Analytical cross-sectional study was conducted on 104 SCIPs treated at our tertiary care hospital. Initial clinical evaluation was done according to the American Spinal Injury Association (ASIA) impairment scale. A clinical evaluation was done. All subjects were screened with the Leeds Assessment of Neuropathic Symptoms, Signs (LANSS) and DN4 questionnaire for neuropathic pain. The Visual Analogue Scale (VAS) was used to measure the severity of neuropathic pain. Later two groups were created based on the presence and absence of neuropathic pain. Results The mean age was 35.04 ± 13 years. Fifty-eight patients (55.8%) had a complete injury (ASIA grade A), 41 (39.4%) patients had an incomplete kind of injury (ASIA grade B-D) and 5(4.8%) patients had no deficits (ASIA grade E). Neuropathic pain was present in 77(74.0%) and absent in 27(26.0%) patients. Seventy-one patients (92.2%) experience neuropathic pain in the first year after traumatic SCI. Medicines were a common pain-relieving factor 64(83.1%). Conclusion 74% of patients complained of neuropathic pain, indicating a significant complication. A comprehensive evaluation and treatment are necessary to address it while including variables like the completeness of injury, duration and timing.

High-throughput transcriptome sequencing reveals the critical role of long non-coding RNA Gm14376 in the occurrence of neuropathic pain

Long noncoding RNAs (lncRNAs) have been suggested as important regulators in neuropathic pain. Our study aims to explore the possible molecular mechanism underlying the role of long non-coding RNA (lncRNA) Gm14376 in neuropathic pain in mice by high-throughput transcriptome sequencing. A mouse model of spared nerve injury (SNI) was constructed for mechanical, thermal and spontaneous pain testing. Transcriptomic changes in lncRNAs and mRNAs in the dorsal root ganglion (DRG) of SNI mice were analyzed using RNA-sequencing techniques in conjunction with public data analysis. AAV5 viral vector was constructed to assess the effect of Gm14376 on SNI-induced pain hypersensitivity and inflammatory response. Cis-target genes of Gm14376 were obtained and the functions of Gm14376 were analyzed by GO and KEGG pathway enrichment analyses. Results from bioinformatic analysis identified a conserved Gm14376, which was up-regulated in the DRG of SNI mice, specifically in response to nerve injury. Overexpression of Gm14376 in DRG induced neuropathic pain-like symptoms in mice. Furthermore, the functions of Gm14376 were related to the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and fibroblast growth factor 3 (Fgf3) was identified as the cis-target gene of Gm14376. Gm14376 could directly up-regulate Fgf3 expression to activate the PI3K/Akt pathway, which alleviated pain hypersensitivity to mechanical and thermal stimuli and reduced the release of inflammatory factors in SNI mice. From our data, we conclude that SNI-induced up-regulation of Gm14376 expression in DRG activates the PI3K/Akt pathway through up-regulation of Fgf3 expression, thereby promoting the development of neuropathic pain in mice.

Prevalence and predisposing factors of neuropathic pain in patients with rotator cuff tears

BackgroundThe management of pain in patients with rotator cuff tears can be challenging. Neuropathic pain is reportedly associated with pain occurrence in musculoskeletal diseases. However, to date, few studies have reported on the prevalence of neuropathic pain in patients with rotator cuff tears or identified the factors associated with neuropathic pain in a multicenter study. MethodsA total of 391 patients (205 males and 186 females; median age, 67.7 years; range, 27–92 years) with rotator cuff tears were included in this study. The prevalence of neuropathic pain in rotator cuff tears was investigated using the Japanese version of the painDETECT questionnaire for all patients. In addition, factors significantly associated with the occurrence of neuropathic pain were examined using multivariate logistic regression analysis. ResultsTwenty-eight patients (7.2%) were classified into the neuropathic pain group (score ≥19), 97 (24.8%) into the uncertainty regarding neuropathy group (score 13–18), and 266 (68.0%) into the nociceptive pain group (score ≤12). According to the multivariate logistic regression analysis, the independent predictors of neuropathic pain were the VAS score (most severe pain during the past 4 weeks; odds ratio, 1.55; 95% confidence interval [CI], 1.23–2.09) and UCLA shoulder score (odds ratio, 0.81; 95% CI, 0.65–0.97). ConclusionsBased on the study findings, the prevalence of neuropathic pain in patients with rotator cuff tear was 7.2%. It is important to investigate the presence or absence of neuropathic pain when treating patients with painful rotator cuff tears, because neuropathy associated with rotator cuff tears may adversely affect patient outcomes.

Systematic Review: Analysis of the Correlation between Neuropathic Pain and VEGF Level

&#x0D; Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Literature search through database PUBMED using the keyword “neuropathic pain” combined with several terminologies such as: 'vascular endothelial growth factor', and 'VEGF'. We take only randomized control trial with English language. We excluded studies that specifically examined another induceable factor which can also cause neuropathic pain. Twenty four hundred and two hundred sixty seven kinds of literature were found, 53 of which were related to neuropathic pain and VEGF, only 6 included the study criteria. The occurrence of neuropathic pain is closely related to increased levels of VEGF-A bound to its receptor, namely VEGFRs. Increased VEGF-A can occur in both the central and peripheral nervous systems which is influenced by various conditions such as hypoxia, inflammation, leukocyte accumulation, increased blood sugar levels in diabetes mellitus, and malignancy. Stem cell therapy with VEGFA has been developed and can be a therapeutic option in neuropathic pain.&#x0D; Keywords: Neuropathic pain, vascular endothelial growth factor&#x0D; &#x0D;

Effect of AMPK Subunit Alpha 2 Polymorphisms on Postherpetic Pain Susceptibility in Southwestern Han Chinese.

IntroductionAdenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2, the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population.MethodsThis study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed.ResultsThe PHN patients were older than the healthy subjects (P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P >0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism (P < 0.05), but not in rs2796498 (P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis (P < 0.05).ConclusionPHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.

Neuropathic pain after spinal intradural benign tumor surgery: an underestimated complication?

Neuropathic pain presents a burdening and impairing condition which may occasionally occur after spinal tumor surgery. While it has been described in peripheral nerve sheath tumors, data on other intradural tumor patients is sparse. We hereby present a large cohort population undergoing different intradural spinal tumor surgery with assessment of early postoperative and follow-up outcomes, focusing on the occurrence of neuropathic pain. We performed a retrospective monocentric study including all patients treated for intradural spinal tumors between 2009 and 2020. We extracted surgical aspects as well as pre- and postoperative clinical courses from the records. Statistical analysis of potential contributing prognostic factors was performed including matched pair analysis. In total, 360 patients were included for analysis. At a median follow-up of 2 years, 26/360 patients complained of a neuropathic pain syndrome (7.2%) requiring continuous medication. Of these patients only 50% complained preoperatively of pain. Tumor entity did not significantly influence the incidence of postoperative neuropathic pain (p = 0.91). Sacrifice of the tumor carrying nerve root and tumor recurrence also did not increase the risk for this condition. Persistent neuropathic pain requiring continuous treatment occurred in 7.2% of patients undergoing intradural spinal surgery in our cohort. This frequently underestimated postoperative adverse event represents a disabling condition leading to a substantial impairment in the quality of life among the affected patients.

The occurrence of neuropathic pain following surgery of brainstem cavernous malformations.

This study aimed to assess the occurrence and significance of postoperative neuropathic pain (NP) in patients with surgically treated brainstem cavernous malformations (BSCMs). Seventy-four BSCM patients surgically treated between 2003 and 2019 were reviewed for the occurrence of postoperative NP and related treatment. The relevance of BSCM location, preoperative characteristics, influence on functional outcome, postoperative health-related quality of life (HRQOL) and life satisfaction was evaluated. Six out of 74 patients (8%) suffered from NP. The Leeds Assessment of Neuropathic Symptoms and Signs scores ranged from 12 to 16 (mean 14.28±1.6). Visual analog scale pain was 5.2±2.0. NP had no effect on preoperative characteristics or functional outcome. Bodily pain (HRQOL) and vocational time (life satisfaction) were significantly decreased in NP compared to non-NP patients. Specific BSCM location (regarding brainstem nuclei involved in pain processing) and other preoperative patient- and BSCM-related parameters were not associated with the occurrence of postoperative NP. Three out of six patients were currently under NP-specific treatment. The proportion of patients suffering from postoperative NP (8%) was substantially higher compared to previously published studies. The pain affected the HRQOL of patients, most of whom were insufficiently treated and not satisfied with treatment results. Our findings may help to raise awareness for postoperative NP in BSCM, which is essential to improve diagnosis and initiation of proper treatment, as well as preoperative informed consent of patients.

Neuropathic Pain: Biomolecular Intervention and Imaging via Targeting Microglia Activation.

Many diseases, including cancer, can lead to neuropathic pain (NP). NP is one of the accompanying symptoms of suffering in many conditions and the life quality of NP patient is seriously affected. Due to complex causes, the effects of clinical treatments have been very unsatisfactory. Many experts have found that neuron-microglia interaction plays an essential role in NP occurrence and development. Therefore, the activation of microglia, related inflammatory mediators and molecular and cellular signaling pathways have become the focus of NP research. With the help of modern functional imaging technology, advanced pre-and clinical studies have been carried out and NP interventions have been attempted by using the different pharmaceuticals and the extracted active components of various traditional herbal medicines. In this communication, we review the mechanism of microglia on NP formation and treatment and molecular imaging technology’s role in the clinical diagnosis and evaluation of NP therapies.

RIP3‐mediated necroptosis increases neuropathic pain via microglia activation: necrostatin‐1 has therapeutic potential

Neuropathic pain (NP) is a clinical symptom that accompanies many diseases. We investigated the effect of receptor‐interacting protein kinase 3 (RIP3)‐regulated necroptosis on NP and explored its relationship with microglia, in order to provide a theoretical basis for further research and provide new insights into the treatment of NP. In this study, the spared nerve injury (SNI) model was used along with intervention with necrostatin and the inhibitor of necroptosis necrostatin‐1 (Nec‐1). Pain behavior tests were performed 1 and 3 days before the nerve injury (or sham) operation, and on days 1, 3, 5, 7, 10, and 14 after the operation. The spinal cord tissues were collected for detection of RIP3 expression and distribution, changes in the number of microglia cells, activation of necroptosis, and the level of proinflammatory factors. Collected spinal cord tissues were analyzed using western blot, immunohistochemistry, immunofluorescence, immunoprecipitation assays, and ELISA, respectively. We found that, compared with the sham group, the expression of RIP3 protein in the spinal cord of rats in the SNI group increased from 3 to 14 days after surgery. Immunofluorescence staining showed that RIP3 was coexpressed with the microglia and the number of microglia increased significantly in the SNI model group. The results of immunoprecipitation assays suggested that a RIP3‐mediated necroptosis pathway promotes NP. After treatment with Nec‐1, the expression of RIP3 protein and the number of microglia were significantly reduced, and the expression levels of TNF‐α, IL‐1β, and IL‐6 in spinal dorsal horns were significantly decreased. These results indicate that RIP3 promotes necroptosis to increase the occurrence of NP via microglia.

Spinal Hemangioblastomas and Neuropathic Pain

Spinal hemangioblastomas (SHs) are rare and benign tumors. Primary symptoms include pain, hypoesthesia, and neuropathic pain (NP). Clinical symptoms may be as a result of tumor mass effect, peritumoral effect, syrinx, or venous congestion. No studies have focused on NP in SHs. The objective of this study was to review the rate and causes of NP in patients with SHs. The present study comprises a retrospective analysis of 13 patients with spinal hemangioblastomas. For the retrospective analysis of the patients, we analyzed the absence or presence of NP in the pre- and postoperative periods and its relationship with the level, location, and size of the tumor, as well as the size and location of the syrinx. Postoperative NP was detected in 6 out of 13 patients. All 6 patients' tumors were located at the dorsal aspect of the spinal cord. There was a predominance of rostral syrinx location in patients with NP. Tumor size and level and syrinx size and level were not found to affect the occurrence of NP. The present study shows that NP is observable in both pre- and postoperative periods. Proximity of the tumor to the dorsal root entry zone, and especially the presence of rostral syrinx, are the main factors affecting postoperative NP symptomatology. It is concluded that the combination of these factors and iatrogenic injury of anatomic pathways of NP within the spinal cord are responsible for postoperative NP.

Nerve Grafting in Head and Neck Reconstruction.

In head and neck reconstructive surgery, especially of the mandible, the long-span processed nerve allograft (PNA) is a technological advancement that provides improved quality of life for patients who require ablative surgery by allowing for functional sensory recovery (FSR) in the majority of patients treated with immediate reconstruction. Recently published clinical prospective and retrospective multisite controlled cohort studies of immediate nerve reconstruction at the time of ablative surgery, including pediatric patient populations, were reviewed for valid and predictable outcomes of FSR following the reconstruction of the inferior alveolar nerve using > 5-cm PNA allografts. Both adult and pediatric patients demonstrate high percentages of FSR within 1 year. Pediatric patients demonstrate robust recovery with 100% reaching FSR within 1 year, whereas 89% of adults achieved FSR during the same time span; the pediatric patient population reached FSR earlier when compared with adults. Control, nonallograft nerve repair patients never achieved FSR, reaching only S2 levels in both adults and pediatric groups. There were no adverse events; in fact, no patients demonstrated the occurrence of neuropathic pain when the nerve repair was performed immediately in contrast to delayed repair states. Long-span (> 5-cm) nerve allografts provide FSR in pediatric patients and the majority of adult patients and should be used in patients who require ablation of the mandible for head and neck reconstruction.

Sleep Characteristics in Diabetic Patients Depending on the Occurrence of Neuropathic Pain and Related Factors.

This study aims to compare the sleep characteristics (structure and quality) in patients with type-2 diabetes mellitus with and without diabetic neuropathic pain (DNP), and to investigate the relationship of sensory phenotypes, anxiety, and depression with sleep quality in DNP patients. A cross-sectional study was performed in patients with type-2 diabetes mellitus and neuropathy. Patients were classified into two groups—with or without neuropathic pain—according to the “Douleur Neuropathique-4 (DN4)” scale. Sleep characteristics and quality (Medical Outcomes Study—MOS-sleep), pain phenotype (Neuropathic Pain Symptom Inventory—NPSI), mood status (Hospital Anxiety and Depression scale—HADS), pain intensity (Visual Analogue Scale—VAS), and quality of life (SF-12v2) were measured. The sample included 130 patients (65 with DNP). The mean scores in all the dimensions of the MOS-sleep scale were higher (more disturbances) in the DNP patients. Higher scores in anxiety or depression, greater intensity of pain or a higher score in the paroxysmal pain phenotype were associated with lower sleep quality in DNP patients. A shorter duration of the diabetes and lower levels of glycated hemoglobin were also associated with lower sleep quality. The results show the relationship between DNP and sleep quality, and the importance of assessing sensory phenotypes and mental comorbidities in these patients. Taking these factors into consideration, to adopt a multimodal approach is necessary to achieve better clinical results.