Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential. Thus, neuropathic pain represents an area of critical unmet medical and novel classes of therapeutics with improved efficacy and safety profiles are urgently needed. The cannabidiol (CBD) structural analogue and novel antagonist of GPR55, KLS-13019, was screened in rat models of neuropathic pain. Tactile sensitivity associated with chemotherapy exposure was induced in rats with once daily 1mg/kg paclitaxel injections for 4 days or 5 mg/kg oxaliplatin every third day for one week. Rats were then administered KLS-13019 or comparator drugs on day 7 in an acute dosing paradigm or days 7-10 in a chronic dosing paradigm and mechanical or cold allodynia was assessed. Allodynia was reversed in a dose-dependent manner in the rats treated with KLS-13019, with the highest dose reverting the response to pre-paclitaxel injection baseline levels with both I.P. and P.O. administration after acute dosing. In the chronic dosing paradigm, 4 consecutive doses of KLS-13019 completely reversed allodynia for the duration of the phenotype in control animals. Additionally, co-administration of KLS -13019 with paclitaxel prevented the allodynic phenotype from developing. Together, these data suggest that KLS-13019 represents a potential new drug for the treatment of neuropathic pain. Significance Statement Chemotherapy-induced neuropathic pain (CIPN) is a common, debilitating side effect of cancer treatment with no known cure. GPR55 antagonist KLS-13019 represents a novel class of drug for this condition that is a potent, durable inhibitor of allodynia associated with CIPN in rats in both prevention and reversal dosing paradigms. This novel therapeutic approach addresses a critical area of unmet medical need.

Neuropathic pain may be present in a proportion of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Its presence may lead to the requirement of altered management approaches in these conditions. This study investigated the prevalence of neuropathic pain in OA as compared to that in RA. Patients with OA and RA were included cross-sectionally if they had no other known neuropathic disorder. The PainDETECT questionnaire was used to assess neuropathic pain. WOMAC and CDAI scores were used to assess disease severity in OA and RA respectively. 69 patients with OA with a mean WOMAC score of 53.30 ± 16.39 and 98 patients with RA with a mean CDAI of 25.48 ± 16.99 were compared. The median PainDETECT score for OA was 13 (0-30) and RA was 5 (0-37) [p<0.001]. 15 patients with OA and six patients with RA were highly likely to have neuropathic pain, while 15 patients with OA and 30 patients with RA were classified as possibly having neuropathic pain. Thus, the proportion of patients free from neuropathic pain was higher in the RA group (63.3%) than in the OA group (39.1%) [p = 0.003]. Both the prevalence and the severity of neuropathic pain were significantly higher in OA than in RA. These findings suggest that neuropathic pain is an important factor in OA, as in RA, and must be considered in management as well as in future research in both these conditions.

Glomus tumors, typically localized in digits, palms, and soles, rarely occur in the posterior cervical region. This case report describes a unique presentation of an epithelioid glomus tumor in a 49-year-old male with a history of progressive occipital headaches. A 49-year-old male, referred with a five-year history of worsening occipital headaches, presented a palpable lesion in the right suboccipital area. MRI identified a 2.3 cm subcutaneous lesion adjacent to the right occipital artery, raising initial suspicion of a schwannoma. Subsequent excisional biopsy unveiled an unexpected diagnosis - an epithelioid glomus tumor. The rarity of glomus tumors in the posterior cervical region, coupled with their potential to mimic neurogenic tumors like schwannomas, underscores the diagnostic complexity. This encounter of a glomus tumor in an uncommon posterior cervical location serves as a pertinent reminder for neurosurgeons to consider atypical differentials. This case underscores the need for heightened clinical vigilance when faced with unusual presentations in neurosurgical practice.

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BACKGROUND: This study aimed to investigate medication prescriptions for patients with myelomeningocele (MMC) across different age groups, particularly in adulthood and after middle age.
METHODS: The Japan Medical Data Center (JMDC) database, based on medical claims data, was utilized for this analysis. Patients were divided into 10-year age groups, and prescriptions for analgesics, anticonvulsants, psychotropic drugs, lifestyle disease-related drugs, drugs for urinary incontinence, and laxatives were examined. To compare the differences in the utilization of medications unrelated to lifestyle-related diseases across different age groups, the data was categorized into three age groups: 19 or under, 20-39, and 40 or older.
RESULTS: Among the 556 MMC patients, the percentage of those regularly prescribed analgesics increased from 2.8% in patients ≤ 19 to 31.7% in patients 40 or older (p < 0.01). Psychotropic medication use also increased with age, rising significantly from 6.3% in patients ≤ 19 to 34.6% in patients 40 or older (p < 0.01). Patients with MMC showed an increasing trend in prescriptions for lifestyle-related disease medications compared to the normal control group. Notably, the percentage of patients in their 30 s taking hypertension medication was 4.9%, significantly higher than the 0.86% in the control group (p = 0.029). In their 40 s, 22.9% of MMC patients were prescribed hyperlipidemia medication, significantly higher than the 3.9% in the control group (p < 0.01).
CONCLUSIONS: Comprehensive multidisciplinary support and follow-up are crucial to enhance the quality of life for MMC patients, with particular attention to pain management, psychological care, and treatment of lifestyle-related diseases.

UNASSIGNED: The pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI.
UNASSIGNED: Sixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord.
UNASSIGNED: In the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001).
UNASSIGNED: Local transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.

BACKGROUND: The authors reported the case of a 66-year-old male patient with a 14-year history of right-sided severe episodic and therapy-resistant cluster headache (CH) who underwent bilateral central lateral thalamotomy (CLT) using incisionless transcranial magnetic resonance imaging-guided focused ultrasound (MRgFUS).
METHODS: The patient experienced a single cluster headache attack 5 weeks after the procedure. There were no more pain attacks over the next 6 years of follow-up.
CONCLUSIONS: This treatment success may indicate a common pathophysiology for CH and neurogenic (neuropathic) pain, which has been treated with CLT for more than 30 years. Further experience is needed to assess the reproducibility of this case.

Vincristine (VCR) is a chemotherapeutic agent widely used in treatment of malignancies. However, VCR has a limitation in use since it commonly causes a painful neuropathy (VCR-induced peripheral neuropathy, VIPN). Inflammatory cytokines secreted by immune cells such as macrophages can exacerbate allodynia and hyperalgesia, because inhibiting the inflammatory response is a treatment target for VIPN. In this study, we investigated whether Trichinella spiralis, a widely studied helminth for its immunomodulatory abilities, can alleviate VCR-induced allodynia. Von Frey test showed that T. spiralis infection improved mechanical allodynia at 10 days after VCR injection. We further observed whether the difference was due to mitigated axon degeneration, but no significant difference between the groups in axonal degeneration in sciatic nerves and intra-epidermal nerve fibers was found. Conversely, we observed that number of infiltrated macrophages was decreased in the sciatic nerves of the T. spiralis infected mice. Moreover, treatment of T. spiralis excretory-secretory products caused peritoneal macrophages to secrete decreased level of IL-1β. This study suggests that T. spiralis can relieve VCR-induced mechanical allodynia by suppressing neuroinflammation and that application of controllable degree of helminth may prove beneficial for VIPN treatment.

BACKGROUND: Development of infrapatellar saphenous neuroma (ISN) is a well-recognized reason for knee pain following total knee arthroplasty (TKA). So far, very few studies have addressed the development of painful ISN after TKA and its impact on functional outcome and patient satisfaction.
OBJECTIVE: To present the results of surgical treatment for ISN after primary TKA, the level of pain relief, and the improvement of knee motion and function.
METHODS: Fifteen patients (13 women, 2 men) with persistent medial pain for more than six months after primary TKA, due to osteoarthritis, underwent surgical excision of ISN. ISN diagnosis was confirmed with the presence of Tinel\'s sign along the course of the infrapatellar branch of the saphenous nerve and with pain relief after selective nerve block using local anesthetic. Component loosening, malalignment, instability and infection were excluded systematically in all patients as a source of pain. Pain relief in terms of visual analog scale (VAS), active knee range of motion (ROM), and the Knee Society Score (KSS) for pain and function were evaluated preoperatively and at least six months postoperatively.
RESULTS: The mean patients\' age was 71.3 ± 5.4 years old. The mean interval between TKA and neuroma excision was 10 mo (range, 6 to 14 mo), while the mean follow-up was 8 mo (range: 6 to 11 mo). All 15 patients experienced almost complete immediate pain relief and resolution of allodynia and hyperesthesia after surgery. Pain on the VAS scale improved from 8.6 ± 1.3 preoperatively to 0.8 ± 0.9 at the final follow-up (P = 0.001). KSS pain and function scores were improved from 49.3 ± 5.9 and 62.7 ± 12.8 before surgery to 91.8 ± 4.2 and 75.3 ± 11.3 after surgery, respectively (P = 0.001 and P = 0.015). Active knee ROM was also increased postoperatively from 96 ± 4 to 105 ± 6 degrees (P = 0.001). There were no complications and no further operations required.
CONCLUSIONS: ISN should be considered a potential cause of persistent pain following TKA. Neuroma excision not only provides immediate pain relief and resolution of symptoms but may also improve the knee range of motion.

Chronic pelvic pain (CPP) is a highly prevalent condition which is underdiagnosed and poorly understood. The purpose of this review is to outline the various aspects of the nature of CPP, including its etiologies, clinical presentation, and nonoperative treatment options. For data collection, a PubMed search was conducted using indexing terms such as chronic pelvic pain and pelvic pain. Literature reviews and studies focusing on etiologies, clinical presentation, and/or the diagnosis of CPP were compiled for review by a team of 3 physiatrists. Studies investigating conservative treatments, medications, and interventional procedures for CPP and related conditions with comparable etiologies were also included. Of the 502 articles retrieved, 116 were deemed suitable by the team for this study. Although CPP is a complex, multifaceted condition, a particular susceptibility to nociceptive stimuli was demonstrated as an underlying theme in its evolution. There are many treatment options currently used; however, more robust evidence, such as randomized controlled trials, are needed before creating comprehensive guidelines for treating CPP.