Neurogenic Pain Research Articles

EGb 761 reduces Ca2+ influx and apoptosis after pentylenetetrazole treatment in a neuroblastoma cell line.

Transient receptor potential (TRP) channels have been found to have significant implications in neuronal outgrowth, survival, inflammatory neurogenic pain, and various epileptogenic processes. Moreover, there is a growing body of evidence indicating that transient receptor potential (TRP) channels have a significant impact on epilepsy and its drug-resistant subtypes. We postulated that EGb 761 would modulate TRPA1 channels, thereby exhibiting anti-inflammatory and neuroprotective effects in a neuroblastoma cell line. Our rationale was to investigate the impact of EGb 761 in a controlled model of pentylenetetrazole-induced generalized epilepsy. We evaluated the neuroprotective, antioxidant and anti-apoptotic effects of EGb 761 both before and after the pentylenetetrazole application in a neuroblastoma cell line. Specifically, we focused on the effects of EGB 761 on the activity of Transient receptor potential (TRP) channels. EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of EGb 761 in the pentylenetetrazole-induced epileptogenesis process. Our basic mechanistic framework for elucidating the pathophysiological significance of fundamental ion mechanisms in a pentylenetetrazole treated neuroblastoma cell line provided compelling evidence for the favorable efficacy and safety profile of Egb 761 in human-relevant in vitro model of epilepsy. To the best of our knowledge, this is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels and measure their activation level in a relevant model of human epileptic diseases.

Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions.

Medial thalamotomies were introduced in the late 1940s. Pain relief was shown to be achieved for all body locations. With some exceptions, these early relatively small series showed frequent, more or less complete recurrence of the original pain. The posterior part of the central lateral nucleus in the human medial thalamus was identified in the 1990s using multiarchitectonic studies and intraoperative single-cell recordings and was confirmed as a surgical target. This retrospective patient series extended over 11 years. Its goal was to demonstrate the efficacy and risk profile of the MR-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) against chronic and therapy-resistant neuropathic (i.e., neurogenic) pain. In this single-center, nonrandomized retrospective cross-sectional analysis of consecutive patients, 63 consecutive MRgFUS CLT interventions were performed in 55 patients. The mean follow-up duration was 55 months. A total of 112 CLT targets were performed, and the CLT was applied bilaterally in 48 patients and contralateral to their pain in 7 patients. Repeat MRgFUS interventions were performed in 8 patients. One serious adverse event with numbness of the upper lip was recorded. The mean pain relief rated by patients was 42% ± 32% at 3 months, 43% ± 36% at 1 year, and 42% ± 37% at the last follow-up (n = 63). The proportions of cases with ≥ 30% pain relief were 65% at 3 months, 63% at 1 year, and 61% at the last follow-up. Good outcomes (≥ 50% pain relief) were found in 54% of patients at 3 months, 49% at 1 year, and 51% at the last follow-up. The reduction in mean VAS scores showed similar percentage reductions as those for pain relief (-41% for continuous pain and -49% for pain attacks) at the 1-year follow-up. The mean frequency of pain attacks was reduced by 92%. Allodynia was reduced or suppressed in 68% of patients and never appeared de novo after MRgFUS CLT. These results suggest that MRgFUS CLT against neuropathic pain is a safe approach and its results are stable over time. At a mean follow-up duration of 55 months, the mean pain relief was 42% and more than 50% of patients still reported ≥ 50% pain relief. Patients with classical and idiopathic trigeminal neuralgia reported a higher mean pain relief compared with the whole patient group.

Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites.

Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

Novel Oral CGRP Receptor Antagonist Atogepant in the Prevention of Migraine.

Advancements in molecular biology and neuroscience have uncovered calcitonin gene-related peptide (CGRP), a neuropeptide consisting of thirty-seven amino acids that plays a crucial role in migraine pathogenesis. CGRP receptor antagonist or gepant is an oral medication that can impede the nociceptive signaling pathway related to CGRP. Atogepant, the latest CGRP antagonist approved by the Food and Drug Administration (FDA) for prophylaxis of episodic migraine, works by non-competitively blocking CGRP receptors, thereby curtailing neurogenic inflammation and pain sensitization. Numerous trials have demonstrated that atogepant is an effective therapy for migraine prevention, with its extended half-life and minimal risks of cardiovascular or liver toxicity making it the first drug in its class primarily authorized for that purpose. In terms of monthly migraine days, monthly headache days, and acute medication usage days, atogepant demonstrated a statistically significant difference from baseline. It was well-tolerated with low adverse event rates. The most commonly reported adverse events were constipation and nausea. Atogepant appears to be beneficial for migraine prevention, and it may be more useful in those who do not want to take the medication as an injection or who do not require a lengthy duration of pharmacological impact. In this article, we provide a systematic review of the literature on atogepant and migraine, emphasizing current achievements in this field of study.

IS A TYPE 2B SHORT STEM ADEQUATE IN PATIENTS WITH PROXIMAL FEMORAL DEFORMITIES?

We sought to determine the short to medium-term clinical and radiographic outcomes using a short stem in young adults with a proximal femoral deformity (PFD).We prospectively studied 31 patients (35 hips) with PFDs treated with an uncemented primary THA using a short stem with cervicometaphyseal fixation between 2011–2018. There were 19 male (23 hips) and 12 female (12 hips) patients, with a mean BMI of 26.7±4.1 kg/m2. Twelve cases had a previous surgical procedure, and six of them were failed childhood osteotomies. Mean age of the series was 44±12 years, mean follow-up was 81±27 months and no patients were lost to follow-up. PFDs were categorized according to a modified Berry´s classification. Average preoperative leg-length discrepancy (LLD) was −16.3 mm (−50 to 2).At a mean time of 81 months of follow-up, survival rate was 97% taking revision of the stem for any reason and 100% for aseptic loosening as endpoints. No additional femoral osteotomy was required in any case. Average surgical time was 66 minutes (45 to 100). There was a significant improvement in the mHHS score when comparing preoperative and postoperative values (47.3±10.6 vs. 92.3±3.7, p=0.0001). Postoperative LLD was in average 1 mm (−9 to 18) (p=0.0001). According to Engh's criteria, all stems were classified as stable without signs of loosening. Postoperative complications included 1 pulmonary embolism, 1 neurogenic sciatic pain, 1 transient sciatic nerve palsy that recovered completely after six months, and 2 acute periprosthetic joint infections. One patient suffered a Vancouver B2 periprosthetic femoral fracture 45 days after surgery and was revised with a modular distally fixed uncemented fluted stem.A type 2B short stem evidenced promising outcomes at short to medium-term follow up in young adult patients with PFDs, avoiding the need for corrective osteotomies and a revision stem.

Comparison of minimally invasive decompression alone versus minimally invasive short-segment fusion in the setting of adult degenerative lumbar scoliosis: a propensity score-matched analysis.

Patients with degenerative lumbar scoliosis (DLS) and neurogenic pain may be candidates for decompression alone or short-segment fusion. In this study, minimally invasive surgery (MIS) decompression (MIS-D) and MIS short-segment fusion (MIS-SF) in patients with DLS were compared in a propensity score-matched analysis. The propensity score was calculated using 13 variables: sex, age, BMI, Charlson Comorbidity Index, smoking status, leg pain, back pain, grade 1 spondylolisthesis, lateral spondylolisthesis, multilevel spondylolisthesis, lumbar Cobb angle, pelvic incidence minus lumbar lordosis, and pelvic tilt in a logistic regression model. One-to-one matching was performed to compare perioperative morbidity and patient-reported outcome measures (PROMs). The minimal clinically important difference (MCID) for patients was calculated based on cutoffs of percentage change from baseline: 42.4% for Oswestry Disability Index (ODI), 25.0% for visual analog scale (VAS) low-back pain, and 55.6% for VAS leg pain. A total of 113 patients were included in the propensity score calculation, resulting in 31 matched pairs. Perioperative morbidity was significantly reduced for the MIS-D group, including shorter operative duration (91 vs 204 minutes, p < 0.0001), decreased blood loss (22 vs 116 mL, p = 0.0005), and reduced length of stay (2.6 vs 5.1 days, p = 0.0004). Discharge status (home vs rehabilitation), complications, and reoperation rates were similar. Preoperative PROMs were similar, but after 3 months, improvement was significantly higher for the MIS-SF group in the VAS back pain score (-3.4 vs -1.2, p = 0.044) and Veterans RAND 12-Item Health Survey (VR-12) Mental Component Summary (MCS) score (+10.3 vs +1.9, p = 0.009), and after 1 year the MIS-SF group continued to have significantly greater improvement in the VAS back pain score (-3.9 vs -1.2, p = 0.026), ODI score (-23.1 vs -7.4, p = 0.037), 12-Item Short-Form Health Survey MCS score (+6.5 vs -6.5, p = 0.0374), and VR-12 MCS score (+7.6 vs -5.1, p = 0.047). MCID did not differ significantly between the matched groups for VAS back pain, VAS leg pain, or ODI scores (p = 0.38, 0.055, and 0.072, respectively). Patients with DLS undergoing surgery had similar rates of significant improvement after both MIS-D and MIS-SF. For matched patients, tradeoffs were seen for reduced perioperative morbidity for MIS-D versus greater magnitudes of improvement in back pain, disability, and mental health for patients 1 year after MIS-SF. However, rates of MCID were similar, and the small sample size among the matched patients may be subject to patient outliers, limiting generalizability of these results.

ID: 203889 Inactivation of Spinal Cord Stimulator Implanted Pulse Generators After Elective Surgery: An Under-Recognized Problem

Spinal cord stimulation (SCS) is an established and effective method for chronic neurogenic pain relief consisting of the placement of an epidural lead and implanted pulse generator (IPG). The electronics of SCS IPGs are susceptible to damage when implanted patients undergo surgery. Some SCSs have a dedicated surgery mode, while others recommend turning the SCS off to protect it from damage. IPG inactivation may require resetting or replacement surgery and the prevalence of this real-world problem has not been studied.

ID: 222711 Fast-Acting Sub-Perception SCS for Lower Back Pain in an Individual With Incomplete Spinal Cord Injury

Spinal cord stimulation (SCS) has been utilized for decades to manage different pain conditions, particularly, those with a neurogenic origin. However, its usefulness and mechanism of action in treating neurogenic pain in individuals with spinal cord injuries remain unclear. Neuropathic pain in SCI is difficult to treat with modalities like dorsal column stimulation due to loss of efficacy over time, incomplete coverage of painful areas, and undesirable paresthesias in unaffected areas.

Overexpression of MicroRNA-182-5p Alleviates Pain in Rats with Lumbar Disc Herniation

Inflammatory factor stimulation secondary to lumbar disc herniation (LDH) is considered to be the main cause of lumbar back and lower extremity pain in patients with LDH. In the meanwhile, microRNAs have been reported to be effective in inhibiting the expression of several inflammatory factors. In the current study, we used rat LDH model to explore the feasibility of MSCs overexpressing microRNA-182-5p as a treatment option for LDH. Changes of inflammatory factors and changes of histological properties of dorsal root ganglion were observed to test the efficacy of this treatment option for lower back and extremity pain due secondary to LDH. All the rats survived by the end of eight week study period. The expression of TNF-α, IL-1, IL-6 both in dorsal root ganglia and blood serum were significantly lower in the experimental group than the control group (P &lt;0.01). Histopathologic examination results showed better preserved tissue structural integrity of nerve ganglion in rats treated with BMSCs overexpressing microRNA-182-5p. Those results indicated that, BMSCs overexpressing microRNA-182-5p can significantly inhibit inflammatory reaction after LDH, and may be used as a therapeutic option to alleviate pain in patients with neurogenic pain after LDH.

Multiple Sclerosis Related Trigeminal Neuralgia – Clinical Characteristics, MRI Correlates and Treatment Outcomes (P12-3.015)

<h3>Objective:</h3> To describe the clinical characteristics, MRI correlates, and treatment outcomes of the University of Utah Multiple Sclerosis (MS) patient population with Trigeminal Neuralgia (TN). <h3>Background:</h3> MS related TN is known to be a challenge to effectively treat and is a major cause of debility for these patients. Despite its impact on quality of life, clinical features and management strategies specific to TN secondary to MS are limited. <h3>Design/Methods:</h3> A prospective review was conducted of patients within the University of Utah Healthcare system who met the following criteria: (1) clinically definite MS (McDonald 2017) (2) met American Academy of Neurology ‘s (AAN) diagnostic criteria for TN (3) were seen at University of Utah MS clinic between the dates of 1/2017 and 9/2022. TN pain was assessed with a questionnaire to determine pain characteristics and severity over time. MRI brain and cervical spine were evaluated for relevant lesions. Treatment (including both pharmacologic and non-pharmacologic) along with outcomes were monitored. <h3>Results:</h3> Fourteen MS patients met inclusion criteria, (11 female, 3 male) with average age being 65 years old. The neurogenic pain quality was electric (10), burning (6), tingling (5), and pins/needles sensation (5) with average severity of 6. Sensory deficits in cranial nerve V (CNV) distribution were noted in 6 patients. Imaging studies were available for 13 patients. Demyelinating lesions were identified in brainstem and CN V (8), dorsolateral upper cervical cord (6), or both brainstem and cord (4). Most patients were treated with oxcarbazepine followed by gabapentin with 1 patient benefiting from 2 gamma knife procedures. <h3>Conclusions:</h3> MS patients with TN experienced neurogenic pain of multiple types and high severity. MRI correlates of TN in brainstem or cervical cord were frequently observed. Pharmacological interventions, especially oxcarbazepine and gabapentin were frequently beneficial. Further evaluation of gamma knife procedure in MS related TN should be investigated. <b>Disclosure:</b> Dr. Germaine has nothing to disclose. Mrs. Steiner has nothing to disclose. The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care.

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.Aim: To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body’s adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

Microneedle-mediated delivery of Ziconotide-loaded liposomes fused with exosomes for analgesia.

Ziconotide (ZIC) is an N-type calcium channel antagonist for treating severe chronic pain that is intolerable, or responds poorly to the administration of other drugs, such as intrathecal morphine and systemic analgesics. As it can only work in the brain and cerebrospinal fluid, intrathecal injection is the only administration route for ZIC. In this study, borneol (BOR)-modified liposomes (LIPs) were fused with exosomes from mesenchymal stem cells (MSCs) and loaded with ZIC to prepare microneedles (MNs) to improve the efficiency of ZIC across the blood-brain barrier. To evaluate local analgesic effects of MNs, the sensitivity of behavioral pain to thermal and mechanical stimuli was tested in animal models of peripheral nerve injury, diabetes-induced neuropathy pain, chemotherapy-induced pain, and ultraviolet-B (UV-B) radiation-induced neurogenic inflammatory pain. BOR-modified LIPs loaded with ZIC were spherical or nearly spherical, with a particle size of about 95nm and a Zeta potential of -7.8mV. After fusion with MSC exosomes, the particle sizes of LIPs increased to 175nm, and their Zeta potential increased to -3.8mV. The nano-MNs constructed based on BOR-modified LIPs had good mechanical properties and could effectively penetrate the skin to release drugs. The results of analgesic experiments showed that ZIC had a significant analgesic effect in different pain models. In conclusion, the BOR-modified LIP membrane-fused exosome MNs constructed in this study for delivering ZIC provide a safe and effective administration for chronic pain treatment, as well as great potential for clinical application of ZIC.

A53 FECAL BIOACTIVE PHOSPHOLIPIDS AS TRIGGERS OF INTESTINAL HYPERSENSITIVITY IN IRRITABLE BOWEL SYNDROME

Abstract Background Chronic abdominal pain is the most common complaint of patients with gastrointestinal disorders. Its treatment is of limited efficacy as the pathophysiology is poorly understood. The gut microbiome has been shown to affect host physiology, including the neural system function, and growing evidence suggests that it plays an important role in pain perception. Gut microbiota produces a large variety of molecules that can regulate pain perception, such as histamine or bioactive lipids. Phospholipid mediators (PLM) are signaling molecules linked to neurogenic pain as by-products of inflammatory processes in mammals. But it is unknown whether bacteria can produce PLM and whether they play any role in visceral hyperalgesia. Purpose To investigate whether PLM are present in stool of patients with chronic abdominal pain, and whether they have potential to induce visceral hypersensitivity. Method Stool samples from 27 patients with irritable bowel syndrome (IBS) were collected both during periods of severe and minimal/no pain. The fecal concentration of two PLM (lipid A and lipid B) was determined by ELISA. The passage of lipid A and lipid B through the intestinal barrier was determined ex vivo using Ussing chambers and in vivo by their intracolonic instillation, and their levels assessed in the serosal compartment and the serum, respectively, by ELISA. We used primary cultures of sensory neurons from the dorsal root ganglia (DRG) of conventional mice (SPF) to study the neuronal activation in vitro. Calcium mobilization in DRG sensory neurons was measured by an inverted fluorescence microscope using a fluorescent probe Fluo-4 (1mM) after stimulation with different concentration of lipid A or lipid B. Visceral sensitivity in vivo after intracolonic instillation of combined lipids A and B was evaluated by colorectal distension. Result(s) The concentration of lipid A (p=0.001) and lipid B (p=0.002) in stool was significantly higher in IBS patients when experiencing severe abdominal pain compared to periods of minimal pain. The concentration of lipid A (p=0.03; p=0.07) and lipid B (p=0.018; p=0.018) in the serosal compartment and in the serum, respectively, was higher compared to the control condition. The percentage of neurons responding to lipid A or lipid B was significantly higher compared to the control condition, at all tested concentrations. Finally, combined lipid A and lipid B induced visceral hypersensitivity within 10 minutes (p=0.0433) and 90 minutes (p=0.0020) after intracolonic instillation. Conclusion(s) Our data suggest that PLM can be found in stool of patients with abdominal pain, that they cross the colonic barrier and increase visceral sensitivity. Further studies are needed to ascertain whether gut bacteria produce these PLM and investigate the precise mechanisms by which PLM induce hyperalgesia. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Weston Family Foundation Disclosure of Interest None Declared

Rectal cancer pelvic recurrence: imaging patterns and key concepts to guide treatment planning.

For rectal cancer, MRI plays an important role in assessing extramural tumor spread and informs surgical planning. The contemporary standardized management of rectal cancer with total mesorectal excision guided by imaging-based risk stratification has dramatically improved patient outcomes. Colonoscopy and CT are utilized in surveillance after surgery to detect intraluminal and extramural recurrence, respectively; however, local recurrence of rectal cancer remains a challenge because postoperative changes such as fat necrosis and fibrosis can resemble tumor recurrence; additionally, mucinous adenocarcinoma recurrence may mimic fluid collection or abscess on CT. MRI and 18F-FDG PET are problem-resolving modalities for equivocal imaging findings on CT. Treatment options for recurrent rectal cancer include pelvic exenteration to achieve radical (R0 resection) resection and intraoperative radiation therapy. After pathologic diagnosis of recurrence, imaging plays an essential role for evaluating the feasibility and approach of salvage surgery. Patterns of recurrence can be divided into axial/central, anterior, lateral, and posterior. Some lateral and posterior recurrence patterns especially in patients with neurogenic pain are associated with perineural invasion. Cross-sectional imaging, especially MRI and 18F-FDG PET, permit direct visualization of perineural spread, and contribute to determining the extent of resection. Multidisciplinary discussion is essential for treatment planning of locally recurrent rectal cancer. This review article illustrates surveillance strategy after initial surgery, imaging patterns of rectal cancer recurrence based on anatomic classification, highlights imaging findings of perineural spread on each modality, and discusses how resectability and contemporary surgical approaches are determined based on imaging findings.

Role of nerve signal transduction and neuroimmune crosstalk in mediating the analgesic effects of acupuncture for neuropathic pain.

Neurogenic pain rises because of nervous system damage or dysfunction and is the most difficult to treat among other pathological pains. Acupuncture has been reported as a great treatment option for neurogenic pain owing to its unlimited advantages. However, previous studies on the analgesic effects of acupuncture for NP were scattered and did not form a whole. In this study, we first comprehensively review the relevant basic articles on acupuncture for NP published in the last 5 years and summarize the analgesic mechanisms of acupuncture in terms of nerve signaling, neuro-immune crosstalk, and metabolic and oxidative stress regulation. Acupuncture inhibits the upstream excitatory system and suppresses neuronal transmission efficiency by downregulating glutamate, NMDA receptors, P2XR, SP, CGRP, and other neurotransmitters and receptors in the spinal cord, as well as plasma channels such as TRPV1, HCN. It can also activate the downstream pain inhibitory pathway by upregulating opioid peptide (β-endorphin), MOR receptors, GABA and GABA receptors, bi-directional regulating 5-hydroxytryptamine (5-HT) and its receptors (upregulate 5-HT 1A and downregulate 5-HT7R) and stimulating hypothalamic appetite-modifying neurons. Moreover, neuroinflammation in pain can be inhibited by acupuncture through inhibiting JAK2/STAT3, PI3K/mTOR pathways, down regulating chemokine receptor CX3CR1 on microglia and up regulating adenosine receptor A1Rs on astrocytes, inhibiting the activation of glia and reducing TNF-α and other inflammatory substances. Acupuncture also inhibits neuronal glucose metabolism by downregulating mPFC's GLUT-3 and promotes metabolic alterations of the brain, thus exerting an analgesic effect. In conclusion, the regulation of nerve signal transduction and neuroimmune crosstalk at the peripheral and central levels mediates the analgesic effects of acupuncture for neuropathic pain in an integrated manner. These findings provide a reliable basis for better clinical application of acupuncture in the management of neuropathic pain.

Etiopathogenetic substantiation of surgical treatment of neurogenic pain syndromes

The purpose of the study was to improve classification of neurogenic (neuropathic) pain syndromes. This will make it possible to define the indications for appropriate analgesic surgery for each type of drug-resistant neurogenic pain syndrome. Incorrect management of neurogenic pain syndromes is usually associated with underestimation of pathogenetic prerequisites for its occurrence. Differentiation of compression, deafferentation and mixed neurogenic pain syndromes makes it possible to determine appropriate surgery and avoid tactical errors. Moreover, this approach allows you to save patients from unreasonable long-standing suffering. Patients with chronic pain syndromes often become disabled, sometimes in the prime of life, and isolated from society and family. Therefore, treatment of chronic pain is currently an urgent problem.

Analysis of changes in the serotonin inactivation coefficient in brain structures with simultaneous modeling of chronic neurogenic pain and malignant neoplasia

Introduction. Chronic pain syndrome in the development of malignant neoplasms has a complex polyethological character. The study of the pathogenetic mechanisms of pain during the growth of the transplanted tumor in the experiment can open up broad perspectives for the creation of new domestic analgesic drugs for use in oncology.Aim. To study the serotonin inactivation coefficient (SIC), the ratio of serotonin (S) and its main metabolite 5-hydroxyindolacetic acid (S-OH) in brain areas (cortex, hypothalamus) with simultaneous modeling of chronic neurogenic pain and malignant neoplasia.Material and Methods. The study involved white mongrel rats (males). To create a model of chronic pain (CP), ligation of the sciatic nerve was performed according to the method of V.V. Kravtsova in modification. Rat sarcoma M-1 was used to simulate malignant neoplasia. At the main stage of the study, the animals were divided into 4 groups: control, two comparison groups (model of chronic pain, standard M-1 sarcoma grafting) and experimental (combined modeling of CP and oncological process). Animals of the second, third and fourth groups were euthanized sequentially at the 2nd and 3rd weeks of the development of the tumor process.Results. Chronic pain syndrome disrupts the process of serotonin metabolism: the decrease in SIC in the cerebral cortex of experimental animals was more significant by 48% (day 14) and 72% (day 21). The development of the oncological process in comparison groups (groups 3a and 3b) is accompanied by a decrease in the level of SIC, more significant at the 21th day of M-1 sarcoma development: by 37% in the hypothalamus, by 41% in the cerebral cortex. With simultaneous modeling of chronic neurogenic pain and malignant neoplasia, the lowest values of the studied indicator were noted, the decrease was 75% in the cerebral cortex (group 4a) and 87% (group 4b).Discussion. Chronic neurogenic pain and M-1 sarcoma development in isolated modeling variants cause a significant decrease in SIC in hypothalamus and cerebral cortex due to disorders of serotonin formation. A more significant disruption of the serotonin mediator system was noted in cerebral cortex which leads to a decrease in the body's adaptive capabilities to pain and a disruption of the regulatory mechanisms of metabolism.Conclusion. Modification of serotonin metabolism can be considered as a potential therapeutic target for the treatment of chronic pain syndrome in oncology.

Psychosocial Considerations in Management of Corticobasal Degeneration in Indian American Population

AbstractBackgroundCorticobasal degeneration (CBD) is a neurodegenerative tauopathy primarily affecting the cerebral cortex and basal ganglia, often featuring cognitive decline and parkinsonism. With no proven treatments for this rare condition, the goals of management are to improve patients' quality of life. We evaluate here the unique psychosocial factors that were considered for two women of Asian Indian descent with CBD.MethodPatient 1 was a 77‐year‐old woman who exhibited short‐term memory loss, and then suffered an acute left anterior cerebral artery territory ischemic stroke with right‐sided hemiparesis and neurogenic pain. MRI Brain confirmed the stroke’s location, but did not account for cognitive decline. Patient 2 was a 75‐year‐old woman who initially experienced dysphagia, and then developed right‐sided hemiparesis, right neck spasms, unstable gait, and short‐term memory loss. MRI Brain and Cervical Spine revealed only showed mild chronic microvascular changes and multilevel cervical spondylosis.ResultsPET‐FDG Brain studies were performed for both patients. Patient 1’s study revealed severe hypometabolism affecting bilateral basal ganglia, bilateral thalami, and left supplementary motor cortex, out of proportion to the known stroke and consistent with CBD. Patient 2’s study revealed mild hypometabolism at the left frontal and parietal lobes, sparing the precuneus and posterior cingulate, also consistent with CBD and helping to explain the right‐sided hemiparesis.ConclusionVarious psychosocial factors were considered during the evaluation and management for both patients. Both had limited English proficiency, so cognitive testing was performed with the aid of a medical interpreter to ensure accurate results. Symptomatic treatment was tailored for each patient: Patient 1 received carbidopa/levodopa for parkinsonian tremors, and Patient 2 received cyclobenzaprine for intermittent muscle spasms. Both patients had multigenerational households, and results and prognoses were discussed with multiple relatives so they could coordinate responsibilities. Both families initially resisted recommendations to have home health aides, expressing their cultural belief that families should take care of their relatives on their own. As we discussed this belief over time, and explained the expected progression of symptoms over time, both families came to be more accepting of introducing home health aides, seeing them as a supplement, and not a replacement, for the family’s role.

Potent Analgesic Action of 2-acetoxy-5-(2-4 (trifluoromethyl)-phenethylamino)-benzoic Acid (Flusalazine) in Experimental Mice.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors are the most widely used drugs to treat pain. Conventional NSAIDs and COX-2 selective inhibitors, however, cause several side effects such as gastric damage, kidney damage, and cardiovascular problems. Our previous study showed that 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid ie, flusalazine (also known as ND-07), which exerts dual actions by serving both as an anti-inflammatory agent and a free radical scavenger, is an effective and safe treatment for severe inflammatory diseases in mice. The goal of the present study was to examine the potential analgesic action and safety of flusalazine in mice models of pain. Flusalazine showed a significant analgesic effect in an acetic acid-induced abdominal constriction model. Likewise, total paw licking was reduced significantly in neurogenic (early stage) and inflammatory (late stage) pain induced by formalin in flusalazine-treated mice. In the tail immersion test, flusalazine significantly increased tail withdrawal time at 2 h after its administration. Also, the formation of paw edema in the flusalazine-treated group was significantly inhibited in a carrageenan-induced inflammatory pain model. Gastric damage was not induced by flusalazine even up to 1000 mg/kg, while aspirin and indomethacin caused critical gastric bleeding. These findings suggest that flusalazine's safety profile and analgesic effects have high translational potential for the clinical treatment of patients experiencing pain.

Complete resolution of chronic cluster headache following central lateral thalamotomy using incisionless MRI-guided focused ultrasound with 6 years of follow-up: illustrative case.

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). 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. 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.