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Objectives: Bupropion is an atypical antidepressant that shows robust efficacy in the regulation of neuropathic pain. Citicoline is a dietary supplement which is used as a neuroprotective agent for central nervous system (CNS) disorders. The probable interaction between bupropion and citicoline on neuropathic pain was assessed in male mice. Methods: Neuropathic pain was induced by sciatic nerve ligation. Neuropathic pain was examined in nerve-ligated mice using tail-flick and hot-plate tests. Results: The results indicated that intraperitoneal (i.p.) administration of citicoline (50 and 100 mg/kg) induced an anti-nociceptive effect in nerve-ligated animals. Similarly, i.p. injection of bupropion (2.5 and 5 mg/kg) induced anti-nociceptive effects in nerve-ligated mice. Co-administration of different doses of bupropion (2.5 and 5 mg/kg) along with a low dose of citicoline (25 mg/kg) caused an anti-nociceptive effect by enhancement of tail-flick and hot plate latencies. Interestingly, there is an additive effect between bupropion and citicoline upon the induction of the anti-nociceptive effect. Conclusions: Based on these results, it can be concluded that there is an interaction between bupropion and citicoline upon induction of an anti-nociceptive effect in nerve-ligated mice. [ABSTRACT FROM AUTHOR]

Lingual nerve injury (LNI) is a rare, serious complication and previous studies include limited numbers of cases. The aim of this retrospective study was to report the neurosensory outcomes for a large patient cohort with permanent LNI and correlate the mechanism of injury (surgical vs non-surgical) to neurosensory characteristics. Demographics, procedural parameters, mandibular third molar (M3) position, surgeon type, neurosensory test results, and symptoms were recorded for 228 patients and analysed. The majority were female (67.1%). Overall, 59.6% of LNIs were caused by M3 removal and 36.4% by local anaesthesia. Complete loss occurred more frequently in surgical LNIs (P = 0.013). The presence of pain did not differ significantly, however the burning type of pain was significantly more frequent in non-surgical LNIs (P = 0.008) along with altered gustation (P = 0.025). The most common M3 position related to LNI was distoangular (40.4%), class III (63.2%), level A (58.1%) (Winter/Pell and Gregory classifications). The majority of patients undergoing M3 removal were >24 years. A total of 71.7% showed no sign of recovery and 5.5% reported further impairment in their condition. Overall, nine patients underwent microsurgical repair. This study presents neurosensory characteristics potentially decisive for timely referral of operable LNIs. [ABSTRACT FROM AUTHOR]

Occlusal and percussion pain may manifest occasionally following endodontic treatment, influencing retreatment decisions. Two cases of periapical neuropathic pain, classified as post-traumatic trigeminal neuropathic pain according to the International Classification of Orofacial Pain, are presented. Although mirogabalin is effective in managing neuropathic pain, there is a lack of clinical reports on its use for occasional post-traumatic trigeminal neuropathic pain after endodontic treatment. These cases highlight clinical symptoms and successful treatment with mirogabalin for post-traumatic trigeminal neuropathic pain after endodontic treatment, providing clinicians a "take-away" lesson for improving patient condition. The patients, referred by their primary dentist due to postendodontic abnormal pain, found no relief with antibiotics or nonsteroidal anti-inflammatory drugs. Although no findings including swelling or periapical radiolucency were observed around the tooth, they experienced occlusal and percussion pain. Local anesthetic testing showed that the pain originated from the peripheral area around the tooth rather than from central sensitization. Dental radiography and cone-beam computed tomography revealed no abnormal findings. Root canal retreatment was performed by a specialist in endodontic treatment. Although endodontic retreatment drastically decreased visual analog scale pain score, pain persisted. Based on the International Classification of Orofacial Pain criteria, diseases other than post-traumatic trigeminal neuropathic pain were excluded. Mirogabalin (10 mg/d) was prescribed once daily before bedtime. Visual analog scale scores gradually and drastically decreased 2 weeks after mirogabalin therapy. Several months later, no recurrence of postendodontic pain was observed after tapering off and discontinuing mirogabalin. These findings suggest the possibility of a new treatment method for post-traumatic trigeminal neuropathic pain after endodontic treatment. [ABSTRACT FROM AUTHOR]

Disorders of the trigeminal nerve, a sensory nerve of the orofacial region, often lead to complications in dental practice, including neuropathic pain, allodynia, and ectopic pain. Management of these complications requires an understanding of the cytoarchitecture of the trigeminal ganglion, where the cell bodies of the trigeminal nerve are located, and the mechanisms of cell-cell interactions. In the trigeminal ganglion, ganglion, satellite, Schwann, and immune cells coexist and interact. Cell-cell interactions are complex and occur through direct contact via gap junctions or through mediators such as adenosine triphosphate, nitric oxide, peptides, and cytokines. Interactions between the nervous and immune systems within the trigeminal ganglion may have neuroprotective effects during nerve injury or may exacerbate inflammation and produce chronic pain. Under pathological conditions of the trigeminal nerve, cell-cell interactions can cause allodynia and ectopic pain. Although cell-cell interactions that occur via mediators can act at some distance, they are more effective when the cells are close together. Therefore, information on the three-dimensional topography of trigeminal ganglion cells is essential for understanding the pathophysiology of ectopic pain. A three-dimensional map of the somatotopic localization of trigeminal ganglion neurons revealed that ganglion cells innervating distant orofacial regions are often apposed to each other, interacting with and potentially contributing to ectopic pain. Elucidation of the complex network of mediators and their receptors responsible for intercellular communication within the trigeminal ganglion is essential for understanding ectopic pain. • The trigeminal ganglion contains nervous system cells and immune system cells. • Cells in the trigeminal ganglion interact via gap junctions and mediators. • 3D topography of trigeminal ganglion is essential for clarifying ectopic pain. • The neuro-immune axis may have neuroinflammatory or neuroprotective effects. • Control of the neuro-immune axis leads to the solution of ectopic pain. [ABSTRACT FROM AUTHOR]

Objective: This study systematically reviewed the literature about sensory retraining effect in comparison to other rehabilitative techniques on cortical reorganization in patients with peripheral neuropathic pain. Type: Systematic review. Literature survey: After an electronic search of PubMed, Web of Science, and Embase, risk of bias was assessed using the revised Cochrane risk of bias tool for randomized controlled trials and the ROBINS‐1 (Risk of bias in non‐randomized studies‐of interventions) for non‐randomized studies of intervention. Methodology: The strength of conclusion was determined using the evidence‐based guideline development approach. Synthesis: Limited evidence indicates a higher increase in cortical inhibition and a higher reduction in cortical activation during a motor task of the affected hemisphere after graded motor imagery compared to wait‐list. Higher reductions in map volume (total excitability of the cortical representation) of the affected hemisphere after peripheral electrical stimulation (PES) were observed when compared to transcranial direct current stimulation (tDCS) or to sham treatment with limited evidence. No other differences in cortical excitability and representation of the affected and non‐affected hemisphere were observed when comparing mirror therapy with sham therapy or tDCS, PES with sham therapy or tDCS, and graded motor imagery with wait‐list. Conclusions: Graded motor imagery and PES result in higher cortical excitability reductions of the affected hemisphere compared to wait‐list, tDCS and sham treatment, respectively. [ABSTRACT FROM AUTHOR]

Painful sensitivity in the hand is commonly seen with neuropathic pain, interfering with daily activities including rehabilitation. However, there are currently several terms used to describe the problem and a lack of guidance on what assessments should be used. To gather expert opinion a) identifying current and common terminology used in hand therapy, b) developing a consensus definition of hypersensitivity, and c) developing consensus guidance on how to best assess allodynia. International e-Delphi survey study. We conducted an e-Delphi consensus study drawing on international experts in hand rehabilitation. We planned up to four rounds of consensus-seeking, defining consensus as 75% or more of participants agreeing with a definition or recommendation. Experts were identified from 21 countries, with the nomination of other experts encouraged for 'snowball sampling'. The first round included clinical vignettes describing 'painful sensitivity of the hand' and asked participants to describe how they would assess each case. Definitions for hypersensitivity, tactile hyperesthesia, and allodynia were also requested. We invited 68 participants: 44 more were added through nominations. Sixty-three agreed to participate and were sent the round one survey; 54 participants from 19 countries completed this survey and were invited to participate in all subsequent rounds. No two definitions of hypersensitivity were the same, while 87% of the definitions for allodynia and 78% for tactile hyperesthesia were concordant with a published taxonomy. Over 700 assessment items were proposed in round one: ultimately 38 items representing eight distinct constructs reached a consensus for assessing allodynia. Therapists definitions were consistent with an existing taxonomy for allodynia. Although hypersensitivity conceptualizations varied regarding the qualities of stimulus and response, a working definition was reached. Recommended assessments were relatively consistent internationally, holistic, and reflected a potential link between allodynia and central sensitization. • We worked with hand therapy experts to define hypersensitivity, distinguishing it from allodynia. • Assessment recommendations for the evaluation of allodynia in the hand were developed by consensus. • More research should: a) confirm reliability and validity of relevant measures for hypersensitivity and allodynia b) address the impact of hypersensitivity on function, mood, participation, and quality of life. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with spina bifida (SB) experience nociceptive and neuropathic pain, and women with SB report more pain. However, the relationship between pain type and gender on pain interference and quality of life (QoL) among individuals with SB is less understood. Objective: To assess relationships among pain interference, pain quality, participation‐related QoL, and gender among adults with SB. Design: Fifty‐one adults with SB completed a self‐report survey assessing SB characteristics, pain severity, pain type, pain interference, and QoL. Setting: Hospital outpatient adult SB clinic. Interventions: Not applicable. Main Outcome Measures: Measures of nociceptive pain quality, neuropathic pain quality, participation‐related QoL, as well as pain interference with general activities, mood, and sleep were selected a priori as study measures. Results: Fifty‐eight percent (N = 30) reported pain and more women than men reported pain (69% vs. 38%, p =.003). Higher general pain interference was associated with lower QoL (r = 0.444, p =.042), but not mood or sleep pain interference (both p's ≥.451). There was no statistically significant difference in pain interference between genders (p =.138). Nociceptive pain was more common. Levels of nociceptive pain were positively associated with general pain interference, sleep pain interference, and mood pain inference. Neither pain type was associated with QoL (both p's >.082). Conclusions: The results from this study reveal key differences/similarities among four interrelated factors: pain, pain interference, QoL, and gender. Pertinent information gathered on pain type and QoL, like increased prevalence of nociceptive pain, can be utilized to formulate proactive and effective treatment plans for individuals with SB that may benefit their sleep pain interference and mood pain interference. [ABSTRACT FROM AUTHOR]

Neuropathic pain is characterized by long-lasting, intractable pain. Sciatic nerve ligation is often used as an animal model of neuropathic pain, and the spared nerve injury (SNI) model, in which the common peroneal nerve (CPN) and tibial nerve (TN) are ligated, is widely used. In the present study, we evaluated the analgesic effect of a cholinergic agonist, carbachol, on a neuropathic pain model prepared by sural nerve (SN) ligation in mice. The SN was tightly ligated as a branch of the sciatic nerve. Mechanical and thermal allodynia, and hyperalgesia were assessed using von Frey filaments and heat from a hot plate. The analgesic effects of intracerebroventricularly-administered morphine and carbachol were compared. SN ligation resulted in a significant decrease in pain threshold for mechanical stimulation 1 day after ligation. In response to thermal stimulation, allodynia was observed at 50°C and hyperalgesia at 53 and 56°C 3 days after ligation. Content of thiobarbituric acid reactive substances (TBARS) in the spinal cord increased significantly at 6 and 12 h after ligation. Acetylcholine content of the spinal cord also increased at 5 and 7 days after ligation. Intracerebroventricular administration of carbachol at 7 days after ligation produced a marked analgesic effect against mechanical and thermal stimuli, which was stronger and longer-lasting than morphine at all experimental time points. These findings suggest that cholinergic nerves are involved in allodynia and hyperalgesia of the SN ligation neuropathic pain model. [ABSTRACT FROM AUTHOR]

One of the most common issues caused by antineoplastic agents is chemotherapy-induced peripheral neuropathy (CIPN). In patients, CIPN is a sensory neuropathy accompanied by various motor and autonomic changes. With a high prevalence of cancer patients, CIPN is becoming a major problem for both cancer patients and for their health care providers. Nonetheless, there are lacking effective interventions preventing CIPN and treating the CIPN symptoms. A number of studies have demonstrated the cellular and molecular signaling pathways leading to CIPN using experimental models and the beneficial effects of some interventions on the CIPN symptoms related to those potential mechanisms. This review will summarize results obtained from recent human and animal studies, which include the abnormalities in mechanical and temperature sensory responses following chemotherapy such as representative bortezomib, oxaliplatin and paclitaxel. The underlying mechanisms of CIPN at cellular and molecular levels will be also discussed for additional in-depth studies needed to be better explored. Overall, this paper reviews the basic picture of CIPN and the signaling mechanisms of the most common antineoplastic agents in the peripheral and central nerve systems. A better understanding of the risk factors and fundamental mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Global participation in running has continued to grow over the last decade, with millions of people running weekly, regardless of distance. These events, particularly endurance running events, require months of progressive training and load adjustment, which, combined with other factors, increase the risk of developing running-related injuries. Inflammation is a natural biological response important for healing in musculoskeletal tissue; however, it may also contribute to the unpleasant experience of pain. Runners may suffer from exercise-induced pain and inflammation, necessitating using analgesics and nonsteroidal anti-inflammatories. Unfortunately, the inappropriate use of these drugs is frequently seen in athletes, which may impact their recovery after injury or general health status. This review presents in brief the current knowledge of running-related pathology and treatment thereof, including considerations of its misuse. [ABSTRACT FROM AUTHOR]

Copyright of Archives Medical Review Journal / Arsiv Kaynak Tarama Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) fixed-dose combination (FTC/TDF) is generally well-tolerated, although treatment-related adverse events have been reported. Methods: We report two cases of persons using FTC/TDF PrEP who had acute neuralgia in a Chinese PrEP demonstration trial. Results: Neurological symptoms subsided upon treatment discontinuation. Symptoms were reported as similar to one case's previous experiences with dolutegravir (DTG) + FTC + tenofovir alafenamide (TAF) (for PEP), leading to permanent discontinuation of PrEP. Conclusion: Acute facial neuralgia appears to be a rare idiosyncratic adverse event to FTC/TDF. HIV PrEP is widely recommended as a crucial measure for HIV prevention. In a demonstration trial in China, this article highlights two cases where facial neuralgia emerged as an unexpected side effect of PrEP medication, not previously mentioned in official prescribing information. These findings deepen our understanding of the potential side effects of emitricitabine/tenofovir disoproxil fumarate use and provide empirical evidence to enhance PrEP implementation further and address the challenges that may arise during its utilisation. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions. As G protein-coupled receptors (GPCRs) are widely distributed throughout the body, including the pain transmission pathway and descending inhibition pathway, the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining momentum. Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects. This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain, and discuss the potential benefits and adverse factors of this treatment. We will also concentrate on the development of biased agonists of GPCRs, and based on important examples of biased agonist development in recent years, we will describe universal strategies for designing structure-based biased agonists. It is foreseeable that, with the continuous improvement of GPCRs allosteric modulation and biased agonist theory, effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety. The allosteric modulation based on four key GPCRs (μ -OR, A 1 R, mGluRs and CBRs) shows promise as a therapeutic strategy for neuropathic pain. Allosteric modulators effectively mitigate non-specific side effects by modulating the affinity or efficacy of the orthosteric ligands, or through biased signaling effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetic neuropathic pain (DNP) is a serious complication for diabetic patients involving nervous system. MicroRNAs (miRNAs) are small-noncoding RNAs which are dysregulated in neuropathic pain, and might be critical molecules for pain treatment. Our previous study has shown miR-184-5p was significantly downregulated in DNP. Therefore, the mechanism of miR-184-5p in DNP was investigated in this study. A DNP model was established through streptozotocin (STZ). The pharmacological tools were injected intrathecally, and pain behavior was evaluated by paw withdrawal mechanical thresholds (PWMTs). Bioinformatics analysis, Dual-luciferase reporter assay and fluorescence-in-situ-hybridization (FISH) were used to seek and confirm the potential target genes of miR-184-5p. The expression of relative genes and proteins was analyzed by quantitative reverse transcriptase real-time PCR (qPCR) and western blotting. MiR-184-5p expression was down-regulated in spinal dorsal on days 7 and 14 after STZ, while intrathecal administration of miR-184-5p agomir attenuates neuropathic pain induced by DNP and intrathecal miR-184-5p antagomir induces pain behaviors in naïve mice. Chemokine CC motif ligand 1 (CCL1) was found to be a potential target of miR-184-5p and the protein expression of CCL1 and the mRNA expression of CCR8 were up-regulated in spinal dorsal on days 7 and 14 after STZ. The luciferase reporter assay and FISH demonstrated that CCL1 is a direct target of miR-184-5p. MiR-184-5p overexpression attenuated the expression of CCL1/CCR8 in DNP; intrathecal miR-184-5p antagomir increased the expression of CCL1/CCR8 in spinal dorsal of naïve mice. This research illustrates that miR-184-5p alleviates DNP through the inhibition of CCL1/CCR8 signaling expression. [ABSTRACT FROM AUTHOR]

Diabetic Peripheral Neuropathy (DPN) causes various physical problems such as the increased risk of falling, loss of balance and coordination while standing or walking, susceptibility to injuries due to sensory loss. The aim of the study was to evaluate and compare the effects of neuropathic pain (NP) in individuals with DPN on balance and gait. This prospective controlled study was conducted on 42 adults aged between 40–65 years. The participants were divided into three groups; individuals with DPN and NP (DPN+NP/n = 14), individuals with DPN without NP (DPN-NP/n = 14), and the control group (n = 14), respectively. The Force Plate system and Core Balance System measured static and dynamic postural balance and stability limits. Gait and dynamic plantar pressure distribution analyses were performed with a computerized gait evaluation system. The score of LANSS, and VAS during gait were higher in DPN+NP group than in DPN-NP (p < 0.05). No significant difference was observed between the groups in balance parameters (p > 0.05). The right-left heel maximum forces were lower in both groups with DPN compared to the control group (p < 0.05). In terms of spatiotemporal parameters of the gait, there was a difference between the groups only in step width and left single support line parameters (p < 0.05). The results of this study indicate that the individuals with DPN have an increased step width, their left single support line was shortened, and the maximum force on the heel decreased. The NP did not cause any change in balance and gait parameters. [ABSTRACT FROM AUTHOR]

Methylphenidate is a psychostimulant that increases dopamine and noradrenaline levels. Recent studies have shown that methylphenidate potentiates the effect of morphine and together suppress acute and chronic pain. In clinical practice, methylphenidate has been used as a treatment for ADHD and changes of pain threshold have been noted in these patients. The aim of this study was to determine the effect of methylphenidate in an animal model of peripheral neuropathic pain. Neuropathic pain was modeled by the chronic constriction of the sciatic nerve (CCI) in Wistar rats. We evaluated the effect of methylphenidate (1 mg/kg, s.c.) on evoked pain (reflex tests - plantar test, vonFrey test and operant test - thermal place preference) and on spontaneous pain (conditioned place preference). CCI induced thermal, mechanical and cold hyperalgesia/allodynia. Methyphenidate suppressed mechanical and cold hyperalgesia/allodynia, while had no effect on thermal one. Therefore, methylphenidate seems to be a new potential pharmacotherapy for the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN) is a common diabetes complication. The prevalence of neuropathy is 55% for type 1 and 66% for type 2 diabetes. In Unani medicine neuropathy is known as Khidr (numbness). It is treated with drugs possessing hypoglycemic and analgesic properties, etc. Habb-e-Asab, a polyherbal Unani formulation used for the treatment of Waja-ul-Asab (neuralgia) is routinely used for its indications in neurological pain in Unani medicine. The aim of this study to investigate the efficacy of Habb-e-Asab in diabetic peripheral neuropathy. Thirty patients with DPN were randomly assigned to test (n=20) and control (n=10) groups in a randomized single-blind placebo control study. For 45 days, the test group was given 250 mg Habb-e-Asab twice a day and the control group 250 mg placebo twice a day. The subjective parameters Pain in feet, burning in feet, and tingling in feet was assessed by the arbitrary scale and VAS fortnightly and objective parameters MNSI, and VPT was assessed in pre–post-treatment. The research drug revealed highly statistically significant with p<0.001 on VAS score and MNSI whereas VPT is significant with p<0.01 on few points. But control group exhibits no significant effect in any of the parameters. No adverse effects had been reported in either group. Our finding indicated that the Habb-e-Asab for 45 days improved and reduced the severity of DPN in a patient with diabetes (CTRI/2018/02/011725). [ABSTRACT FROM AUTHOR]

Copyright of Cirugía Plástica Ibero-Latinoamericana is the property of Cirugia Plastica Ibero-Latinoamericana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Impacted teeth is one that fails to erupt into the oral cavity within the estimated time. Neurological disorder are diseases of the central nervous system caused by injury to the brain, spinal cord, or nerves. The examples of neurological disorders are neuralgia and cephalgia. Impacted teeth can put persistent pressure on nerve endings and cause pain in the form of headaches which can reduce the patient's quality of life. In a population with impacted teeth, 53.33% complained a rather disturbing headache and 13.33% of the sample complained headaches that interfered with their activities. Studying the relations between neurological disorder and impacted teeth. Impacted teeth may be associated with neurological disorders such as neuralgia and cephalgia due to persistent pressure from impacted teeth on the nerve endings in contact with them. Impacted teeth may be associated with neurological disorders such as neuralgia and cephalgia. [ABSTRACT FROM AUTHOR]

Vincristine, a widely used chemotherapeutic agent for treating different cancer, often induces severe peripheral neuropathic pain. A common symptom of vincristine-induced peripheral neuropathic pain is mechanical allodynia and hyperalgesia. However, mechanisms underlying vincristine-induced mechanical allodynia and hyperalgesia are not well understood. In the present study, we show with behavioral assessment in rats that vincristine induces mechanical allodynia and hyperalgesia in a PIEZO2 channel-dependent manner since gene knockdown or pharmacological inhibition of PIEZO2 channels alleviates vincristine-induced mechanical hypersensitivity. Electrophysiological results show that vincristine potentiates PIEZO2 rapidly adapting (RA) mechanically-activated (MA) currents in rat dorsal root ganglion (DRG) neurons. We have found that vincristine-induced potentiation of PIEZO2 MA currents is due to the enhancement of static plasma membrane tension (SPMT) of these cells following vincristine treatment. Reducing SPMT of DRG neurons by cytochalasin D (CD), a disruptor of the actin filament, abolishes vincristine-induced potentiation of PIEZO2 MA currents, and suppresses vincristine-induced mechanical hypersensitivity in rats. Collectively, enhancing SPMT and subsequently potentiating PIEZO2 MA currents in primary afferent neurons may be an underlying mechanism responsible for vincristine-induced mechanical allodynia and hyperalgesia in rats. Targeting to inhibit PIEZO2 channels may be an effective analgesic method to attenuate vincristine-induced mechanical hypersensitivity. Vincristine leads to the swelling of DRG neurons, increases their membrane tension and promotes PIEZO2 channel membrane trafficking, which results in the potentiation of PIEZO2 mechanically-activated currents, thereby mediates vincristine-induced mechanical hypersensitivity. [Display omitted] [ABSTRACT FROM AUTHOR]

Peripheral nerve glomus tumors are extremely rare and occur with typical symptoms of peripheral neuropathic pain. Clinicians hardly consider this entity when faced with the swelling of a peripheral nerve and the diagnosis is reached only with histological examination. Nerves of limbs are usually affected and the solid glomus tumor is the most frequent histological variant. A 55-year-old man presented with a glomus tumor of the anterior supraclavicular nerve of the left cervical plexus, misdiagnosed clinically and radiologically as neuroma. Despite the preoperative suspicion and the intraoperative appearance, the histological examination revealed a glomus tumor with a prevalent muscular component, a glomangiomyoma. Once the tumor was removed, pain regressed completely. Because of its rarity, pre-operative diagnosis of glomus tumors is still a challenge, especially when arising from peripheral nerves. In the presence of chronic localized neuroma-type pain and sensitivity, glomus tumors should be considered in the pool of differential diagnosis, even if the imaging is not conclusive. [ABSTRACT FROM AUTHOR]

Management of persistent idiopathic facial pain (PIFP) can be challenging. Sphenopalatine ganglion (SPG) has been the target for the interventional treatment of many facial pain syndromes. However, possible factors that may affect SPG block success are unknown. It was aimed to investigate the effect of neuropathic pain on SPG block outcomes in PIFP, which includes a heterogeneous patient group. All of the patients underwent fluoroscopy-guided SPG block with an injection of 40 mg of 2% lidocaine and 8 mg of dexamethasone. The patients were assigned to 2 groups according to existence of neuropathic pain determined with the DN4 questionnaire score: 19 patients with neuropathic pain (Group 1) and 15 patients without neuropathic pain (Group 2). Preprocedural and postprocedural Visual Analog Scale (VAS) scores were compared between the 2 groups. The mean age of the patients was 47.65 ± 6.50 years. The average pain duration was 52.95 ± 34.81 weeks. A significantly greater decrease was detected in the VAS scores at 1 week (p = 0.036) and 1 month (p < 0.001) in Group 1 when compared to Group 2. Moreover, the proportion of patients with >50% improvement in the VAS scores at 1 week (p = 0.012) and 1 month (P = 0.017) was significantly lower in Group 1 than in Group 2. SPG block appears as a safe, effective, and rapid method to treat PIFP, especially in cases with neuropathic pain. Neuropathic pain may be a predictor for pain relief in interventional procedures targeting SPG in the treatment of PIFP. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Neuropathic pain is regulated by several metabolites of the kynurenine pathway (KYNA-kynurenic acid, and QA-quinolinic acid). Diclofenac exerts analgesic and anti-hyperalgesic effects and also alters KYNA levels, indicating a potential for therapy. We aimed to assess the nociceptive effects of different doses of diclofenac treatment in a rat model of neuropathic pain, and to determine potential relationships with KYNA and QA levels (Graphical Abstract). MATERIALS AND METHODS: Twenty-eight Sprague-Dawley rats were divided into four groups: 40 mg/kg/day diclofenac (high-dose), 20 mg/kg/day diclofenac (normal-dose), non-treatment, and sham. Except for the sham group, the others underwent partial sciatic nerve ligation (left). Baseline (day 0) and post-treatment (day 3) KYNA and QA levels were measured. Allodynia and pain detection were assessed with the von Frey and hot plate tests. RESULTS: Baseline findings were similar in all groups. Compared to baseline, the non-treatment group had significantly worse allodynia on day 3. Baseline and post-treatment von Frey results (left) remained similar in the normal-dose diclofenac group (p=0.336); however, this benefit was not observed in the high-dose group. Relative to baseline, normal-dose diclofenac recipients had significantly higher KYNA concentration (p=0.046) and KYNA-to-QA ratio (p=0.028) on day 3. CONCLUSIONS: Our results show that 3-day therapy with 20 mg/kg/day diclofenac can improve nociceptive findings in neuropathic pain, and that this effect may be associated with increased KYNA or KYNA-to-QA ratio. The lack of dose-dependent effects may be associated with potential adverse influences of exceedingly high diclofenac dosage. [ABSTRACT FROM AUTHOR]

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle , showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N -Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF. Target profiling via thermal proteome profiling reveals that NSF-mediated trafficking of Cav2.2 is a promising approach to alleviating neuropathic pain. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To demonstrate the feasibility of a combined decompression of pudendal and inferior cluneal nerves for entrapment syndrome using a transperitoneal robotic laparoscopy. Demonstration of our 4-step technique with narrated video footage. Pudendal and inferior cluneal neuralgias caused by an entrapment syndrome are both responsible for perineal pain [1]. Although more precise data are lacking, these 2 neuralgias are frequently associated. Failure of surgical pudendal nerve decompression in the early 2000 has driven to discover the entity of a potential entrapment syndrome of the posterior cutaneous nerve of the tight and its inferior cluneal branches between the ischium bone and the sacrotuberous ligament [2]. The corresponding neuralgia is responsible for a neuropathic pain to a more posterior part of the perineum and the thigh, without any neurovegetative symptom. In case of failure of medical treatment, surgery can be proposed using an invasive open transgluteal approach as a standard treatment [3–5]. Transperitoneal robotic laparoscopy for a mini-invasive releasing of both pudendal and inferior cluneal nerves, following a 4-step technique: 1. Opening of the peritoneum between the external iliac vessels and the umbilical ligament 2. Dissection of the internal iliac and pudendal arteries up to the pudendal nerve 3. Section of the sacrospinous ligament and release of the pudendal nerve 4. Section of the sacrotuberous ligament and release of the inferior cluneal nerve Previously, pudendal and inferior cluneal neuralgias have been managed with an invasive open transgluteal surgery. Here, we demonstrate the feasibility of a mini-invasive transperitoneal robotic laparoscopy, with a standardized 4-step surgical technique. [Display omitted] [ABSTRACT FROM AUTHOR]

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β -arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood–brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy. WLB-73502 is a bispecific sigma-1 antagonist and partial mu-opioid agonist (low intrinsic efficacy at G i/o -protein activation and undetectable β -arrestin-2 recruitment) with improved antinociceptive and safety profile respect to strong opioids. [Display omitted] [ABSTRACT FROM AUTHOR]

To describe the prevalence and characteristics of spinal cord injury (SCI)-related pain during initial inpatient rehabilitation and to investigate relationships with demographic and lesion characteristics. Cohort during inpatient rehabilitation. Eight specialized SCI rehabilitation centers in the Netherlands. Patients with newly acquired SCI admitted for inpatient rehabilitation between November 2013 and August 2019 (N=1432). Not applicable. Presence of pain at admission and discharge. Logistic regression analyses were used to study the prevalence of pain related to sex, age, etiology, completeness, and level of injury. Data from 1432 patients were available. Of these patients 64.6% were male, mean age was 56.8 years, 59.9% had a nontraumatic SCI, 63.9% were classified as American Spinal Cord Injury Association Impairment Scale (AIS) D and 56.5% had paraplegia. Prevalence of pain was 61.2% at admission (40.6% nociceptive pain [NocP], 30.2% neuropathic pain [NeuP], 5.4% other pain) and 51.5% at discharge (26.0% NocP, 31.4% NeuP, 5.7% other pain). Having NocP at admission was associated with traumatic SCI. AIS B had a lower risk of NocP than AIS D at admission. Having NocP at discharge was associated with female sex and traumatic SCI. AIS C had a lower risk of NocP at discharge than AIS D. Having NeuP at admission was associated with female sex. Having NeuP at discharge was associated with female sex, age younger than 65 years vs age older than 75 years and tetraplegia. SCI-related pain is highly prevalent during inpatient rehabilitation. Prevalence of NocP decreased during inpatient rehabilitation, and prevalence of NeuP stayed the same. Different patient and lesion characteristics were related to the presence of SCI-related pain. Healthcare professionals should be aware of these differences in screening patients on presence and development of pain during inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

Intracarpal injection of steroids has produced favorable effects in patients with carpal tunnel syndrome (CTS); however, it still carries some drawbacks. Perineural midazolam injection has some promising effects in chronic neuralgia. This study focused upon pain visual analog scale (VAS) improvement, and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) improvements when comparing intracarpal injection of midazolam versus dexamethasone. One hundred and thirty-four patients with mild to moderate CTS were randomized (1:1 ratio) to receive intracarpal 3 ml bupivacaine 0.5% with either 8 mg dexamethasone in 2 ml saline (group DX) or 2 mg midazolam in 2 ml saline (group MZ). VAS and BCTQ were assessed preintervention and postintervention (1st week, 1st, 3rd, and 6th months) The VAS showed a significantly lower value in MZ than the DX group with median value of 2 (maximum-minimum = 1–3) in MZ and 4 (2–5) in DX by the 6th month p = 0.049. Intragroup comparison of follow-up VAS to the baseline value showed significant decreases in the MZ group during the whole study period, whereas in DX the decrease was noticed by the 1st week and 1st month only. In postinterventional BCTQ, both symptom severity (SSS) and functional severity (FSS) scores were significantly lower in MZ rather than DX group after the 1st, 3rd, and 6thmonths where SSS (p = 0.029, 0.048, 0.04) and FSS (p = 0.04, 0.019, 0.003) in consequence. Intracarpal injection of midazolam offers a longer duration of pain relief and higher hand functional improvement scores in comparison to dexamethasone. [ABSTRACT FROM AUTHOR]

• Inflammatory mechanisms play a pivotal role in the development of sciatica associated with LDH. • Inflammatory cytokines and chemokines can be released from herniated disc material. • Inflammatory processes occur independently and persist even after herniation reduction. • Anti-inflammatory therapies and immunomodulatory approaches may offer promising treatment options for patients suffering from sciatica associated with LDH. Lumbar disc herniation frequently causes low back pain and sciatica, significantly impacting patients' quality of life. The pathogenesis of sciatica is complex, involving both mechanical compression and inflammatory processes. Recent studies have suggested a potential role of inflammatory mechanisms in the development of sciatica. We hypothesize that these inflammatory mediators contribute to the neuropathic pain experienced by patients with lumbar disc herniation. Understanding these inflammatory mechanisms may lead to novel therapeutic targets for managing sciatica in lumbar disc herniation, ultimately improving patient outcomes. Future research should focus on testing this hypothesis through scientific investigation to validate these potential new therapies. [ABSTRACT FROM AUTHOR]

Sixty percent of breast cancer patients develop persistent upper limb pain and dysfunction, but only limited knowledge exists about how these symptoms relate to rehabilitation access. A postal survey was sent to patients treated at a London University Teaching Hospital (2018–2020). Data were collected on pain (Pain Detect), shoulder function (Disability of Shoulder Arm and Hand (DASH)), quality-of-life (QoL) (EQ-5D-5L), and clinical characteristics, including treatment and access to rehabilitation. The free-text section invited patients' comments on upper limb symptoms and management strategies, which were analysed thematically. Quantitative data were analysed descriptively, and the medians were examined with Mann-Whitley U-Tests or Kruskal-Wallis Test. Of 511 patients surveyed, 162 (32 %) questionnaires were returned and analysed. Respondents' mean age was 62 years (SD 11.3). The majority had Sentinel Node Biopsy 71 % (116/162) and mastectomy 61 % (99/162). 73 % (119/162) reported pain. Mean (SD) Pain Detect and DASH Score were respectively 11.07 (7) and 21.7 (21.5), with 51 % recording significant shoulder dysfunction, and only 28 % reporting access to rehabilitation. Individuals with neuropathic pain had significantly higher median (range) DASH score 60.8 (35.8, 75.0) p = 0.000. Median DASH score for sedentary individuals was significantly higher 22.9 (7.9, 31.8) p = 0.0009. Free-text analysis revealed persistent, progressive symptoms, mixed attitudes towards exercise and variations in access to rehabilitation and support. Two years following surgery many patients reported significant upper limb symptoms which adversely impact on QoL. However, approximately two thirds did not access potentially beneficial rehabilitation treatments. There is a need to improve pathways of care. Synopsis: Cross-sectional study exploring the prevalence, nature, impact and management of upper limb pain and functional morbidity in individuals treated for breast cancer, identifying challenges in access to care and rehabilitation, to underpin the development of improved care pathways. [ABSTRACT FROM AUTHOR]

• Pain in disc induced LSR is not only mechanical and inflammatory. • BDNF was found to be involved in pain behavior modulation and central pain sensitization in disc induced LSR. • Assessment of BDNF in LSR may help quantify central pain sensitization. • BDNF significantly increases in patients with LSR and correlates with the acute pain severity. Pain is the major cause of disability in disc induced lumbosacral radiculopathy (LSR) and is related to neurotrophins mainly brain derived neurotrophic factor (BDNF). However, to our knowledge evaluating serum BDNF in disc induced LSR has not been reported before. This study was done to investigate serum BDNF in LSR patients and its relation to pain severity and functional disability. This case–control study included 40 disc induced LSR patients and 40 age and sex matched healthy subjects. All patients were subjected to neurological examination, electrophysiological evaluation, pain severity assessment using numerical rating scale (NRS) and functional disability assessment using Modified Oswestry Low Back Pain Disability Index (ODI) and Maine-Seattle Back Questionnaire (MSBQ). According to Douleur neuropathique 4 (DN4) questionnaire, patients were divided into those with neuropathic pain and those with non-neuropathic pain. Serum BDNF was measured by enzyme-linked immunosorbent assay in all participants. Serum BDNF was significantly higher in LSR patients than in healthy controls (U=272.5, P<0.001). Moreover, serum BDNF was significantly higher in those with neuropathic pain compared to those with non-neuropathic pain (U=35, P=0.03). Serum BDNF had a significant positive correlation with NRS score among those with acute pain (r s= 0.537, P=0.026), however there was no significant correlation among those with chronic pain. Furthermore, BDNF had no significant correlation with modified ODI and MSBQ. Increased serum BDNF may be associated with neuropathic pain and acute pain severity in disc induced LSR. However, it may not be related to chronic pain severity or functional disability. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dinutuximab (ch14.18) was the first approved monoclonal antibody against the tumor‐associated antigen disialoganglioside GD2. Despite its success in treating neuroblastoma (NB), it triggers a significant amount of neuropathic pain in patients, possibly through complement‐dependent cytotoxicity (CDC). We hypothesized that modifying ch14.18 using antibody engineering techniques, such as humanization, affinity maturation, and Fc engineering, may enable the development of next‐generation GD2‐specific antibodies with reduced neuropathic pain and enhanced antitumor activity. In this study we developed the H3‐16 IgG1m4 antibody from ch14.18 IgG1. H3‐16 IgG1m4 exhibited enhanced binding activity to GD2 molecules and GD2‐positive cell lines as revealed by ELISA, and its cross‐binding activity to other gangliosides was not altered. The CDC activity of H3‐16 IgG1m4 was decreased, and the antibody‐dependent cellular cytotoxicity (ADCC) activity was enhanced. The pain response after H3‐16 IgG1m4 antibody administration was also reduced, as demonstrated using the von Frey test in Sprague–Dawley (SD) rats. In summary, H3‐16 IgG1m4 may have potential as a monoclonal antibody with reduced side effects. [ABSTRACT FROM AUTHOR]

This article discusses pediatric trigeminal neuralgia, a chronic condition characterized by severe facial pain in the trigeminal nerve distribution. While this condition is more commonly seen in older individuals, it is exceedingly rare in the pediatric population. The article emphasizes the importance of timely diagnosis and intervention, as trigeminal neuralgia can significantly impact a child's quality of life. The case report presented in the article highlights the need for comprehensive diagnostic assessment and multidisciplinary collaboration for optimal patient outcomes. [Extracted from the article]

Objectives: Patients with malignant diseases are known to have a high symptom burden including pain, and insufficient treatment of pain in this population has been frequently documented. To promote the integration of specialized palliative care and hematology and oncology, this study investigated disease, treatment, and comorbidity related symptoms as well as functional capacity and health-related quality of life (HQoL) by patient-reported outcome measures (PROMs) and clinician-reported outcome measures (ClinROs) among inpatients in a comprehensive cancer center. Methods: This cross-sectional study was carried out in a large comprehensive cancer centre of both oncological and hematological inpatients. It combined the use of PROMs and ClinROs. Results: A high symptom burden was reported with fatigue and appetite loss as the most frequent symptoms, and role function being the most impaired function. Further, a low HQoL score was associated with a high number of symptoms/impairments. More than half of all patients reported pain in the last 24 h. Out of 95 patients with average pain >0 in the last 24 h, 71% were treated with opioids and 24% were treated with adjuvant analgesic (AA) defined as antiepileptics, antidepressants and prednisolone. Out of 57 patients with average pain >0 in the last 24 h and possible neuropathic pain, 33% were treated with AAs. A high odds ratio for moderate/severe pain in patients with possible neuropathic pain mechanisms was observed. Conclusions and implications: This study did not only emphasize the need for systematic use of PROMs to identify symptoms and needs for inpatients, but also displayed why PROMs supported by ClinROs are a prerequisite to deliver truly individualized and high-quality patient-centered care. This study calls for continuous training of health care professionals to deliver high-quality treatment of pain. Further, it contributes to the growing recognition, that palliative care and standard care must be integrated to strengthen patient-centered care. [ABSTRACT FROM AUTHOR]

Current treatment options for diabetic neuralgia are limited and unsatisfactory. Tanezumab, a monoclonal antibody that blocks nerve growth factor (NGF) signaling, has been shown to be effective in relieving the clinical symptoms of osteoarthritis pain, chronic low back pain, cancer pain induced by bone metastasis, and diabetic neuralgia. However, the clinical development of tanezumab has been terminated due to the risk of induction of rapidly progressive osteoarthritis (RPOA), and no other NGF antibodies have been examined for their ability to treat diabetic neuralgia in either animal models or clinical trials. In this study, a humanized highaffinity NGF monoclonal antibody (mAb), huAb45 that could neutralize the interaction between NGF and its high-affinity receptor TrkA. In a mouse diabetic neuralgia model, it effectively relieved neuropathic pain. This study may serve as the necessary foundation for future studies of huAb45 to potentially treat diabetic neuralgia. [ABSTRACT FROM AUTHOR]

Copyright of Cukurova Medical Journal / Çukurova Üniversitesi Tip Fakültesi Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)