Pain Sensation Research Articles

Antinociceptive Behavior, Glutamine/Glutamate, and Neopterin in Early-Stage Streptozotocin-Induced Diabetic Neuropathy in Liraglutide-Treated Mice under a Standard or Enriched Environment

Diabetic neuropathy (DN) is a common complication of long-lasting type 1 and type 2 diabetes, with no curative treatment available. Here, we tested the effect of the incretin mimetic liraglutide in DN in mice with early-stage type 1 diabetes bred in a standard laboratory or enriched environment. With a single i.p. injection of streptozotocin 150 mg/kg, we induced murine diabetes. Liraglutide (0.4 mg/kg once daily, i.p. for ten days since the eighth post-streptozotocin day) failed to decrease the glycemia in the diabetic mice; however, it alleviated their antinociceptive behavior, as tested with formalin. The second phase of the formalin test had significantly lower results in liraglutide-treated mice reared in the enriched environment vs. liraglutide-treated mice under standard conditions [2.00 (0.00–11.00) vs. 29.00 (2.25–41.50) s, p = 0.016]. Liraglutide treatment, however, decreased the threshold of reactivity in the von Fray test. A significantly higher neopterin level was demonstrated in the diabetic control group compared to treatment-naïve controls and the liraglutide-treated diabetic mice (p < 0.001). The glutamine/glutamate ratio in both liraglutide-treated groups, either reared under standard conditions (p = 0.003) or an enriched environment (p = 0.002), was significantly higher than in the diabetic controls. This study demonstrates an early liraglutide effect on pain sensation in two streptozotocin-induced diabetes mouse models by reducing some inflammatory and oxidative stress parameters.

Analgesic activity of a new cannabinoid CB1 receptor modulator

Aim. To study the analgesic activity, the effect on motor functions, and the potential ulcerogenic effect of a new 2H-chromene derivative, a cannabinoid CB1 receptor modulator (code name – CHR).Materials and methods. The analgesic activity of the CHR compound was studied when injected intragastrically at an effective dose of 5 mg / kg in mouse models of acute chemogenic pain (formalin test), acute visceral pain (the acetic acid-induced writhing test), and thermal nociception (hot plate test and tail-flick test). It was compared to the effect of tramadol and morphine or diclofenac sodium at doses of 20, 4 or 10 mg / kg, respectively. The effect of a single intragastric injection of the CHR compound at a dose of 5 mg / kg on motor activity was evaluated in the open field test. The potential ulcerogenic effect of the CHR compound at a dose of 5 mg / kg with repeated intragastric administration was compared with the effect of diclofenac sodium at a dose of 10 mg / kg.Results. With subplantar administration of formalin to mice, the 2H-chromene derivative reduced the number of pain reactions by 43–63% (p < 0.05). With intraperitoneal administration of acetic acid to mice, it reduced the number of writhing responses by 50% and had the same analgesic effect as diclofenac sodium and tramadol. In the hot plate test, the CHR compound increased the latency time to painful stimuli by 34% (p < 0.05). In the tailflick test, it increased the latency time to painful thermal sensations by 32% (p < 0.05). The CHR compound at an effective dose of 5 mg / kg did not change the motor activity of mice in the open field test and did not cause the formation of erosions and ulcers in the gastric mucosa when administered repeatedly to rats.Conclusion. The 2H-chromene derivative CHR at an effective dose of 5 mg / kg has a pronounced analgesic effect in mouse models of chemogenic, visceral, and thermal pain, which is as strong as that of tramadol, morphine, and diclofenac sodium used at effective doses. The CHR compound at an effective dose does not inhibit motor functions and does not have an ulcerogenic effect.

A RETREG1 variant is associated with hereditary sensory and autonomic neuropathy with acral self-mutilation in purebred German Spitz.

Hereditary sensory and autonomic neuropathies (HSAN) represent a group of genetic diseases affecting the peripheral nervous system. In humans, at least 16 loci have been associated with the disorder but do not explain the disease origin of all patients. In dogs, similar conditions have been documented for decades in various breeds with a severe impact on life quality and are often referred to as acral mutilation syndrome (AMS). Causal variants in three genes have been identified to date, suggesting larger genetic heterogeneity in the dog population. Our aim was to explain the genetic etiology of an early-onset HSAN/AMS in a purebred German Spitz. The affected dog showed progressive loss of pain sensation in the distal extremities, which led to intense licking, biting, and self-mutilation of digits and paw pads. Whole-genome sequencing identified a single candidate causal variant on chromosome 4 in the RETREG1 gene (c.656C>T, p.Pro219Leu). This missense variant was previously recognized as deleterious in a mixed breed dog family with similar clinical signs. Haplotype analyses and targeted genotyping revealed a likely German Spitz ancestry of these mixed breed dogs. Further screening of an extensive cohort of ~900 000 dogs of various breeds hinted at the variant allele origin in the German Spitz breed. Disruption of RETREG1 inhibits endoplasmic reticulum turnover and leads to neuron degeneration. Our findings provide evidence that this variant underlies the recessive form of HSAN/AMS in the German Spitz and support the use of whole-genome sequencing-based veterinary precision medicine for early diagnosis and prevention via a genetic test.

Investigating Mechanically Activated Currents from Trigeminal Neurons of Non-Human Primates.

Pain sensation has predominantly mechanical modalities in many pain conditions. Mechanically activated (MA) ion channels on sensory neurons underly responsiveness to mechanical stimuli. The study aimed to address gaps in knowledge regarding MA current properties in higher order species such as non-human primates (NHP; common marmosets), and characterization of MA currents in trigeminal (TG) neuronal subtypes. We employed patch clamp electrophysiology and immunohistochemistry (IHC) to associate MA current types to different marmoset TG neuronal groups. TG neurons were grouped according to presumed marker expression, action potential (AP) width, characteristic AP features, after-hyperpolarization parameters, presence/absence of AP trains and transient outward currents, and responses to mechanical stimuli. Marmoset TG were clustered into 5 C-fiber and 5 A-fiber neuronal groups. The C1 group likely represent non-peptidergic C-nociceptors, the C2-C4 groups resembles peptidergic C-nociceptors, while the C5 group could be either cold-nociceptors or C-low-threshold-mechanoreceptors (C-LTMR). Among C-fiber neurons only C4 were mechanically responsive. The A1 and A2 groups are likely A-nociceptors, while the A3-A5 groups probably denote different subtypes of A-low-threshold-mechanoreceptors (A-LTMRs). Among A-fiber neurons only A1 was mechanically unresponsive. IHC data was correlated with electrophysiology results and estimates that NHP TG has ∼25% peptidergic C-nociceptors, ∼20% non-peptidergic C-nociceptors, ∼30% A-nociceptors, ∼5% C-LTMR, and ∼20% A-LTMR. Overall, marmoset TG neuronal subtypes and their associated MA currents have common and unique properties compared to previously reported data. Findings from this study could be the basis for investigation on MA current sensitizations and mechanical hypersensitivity during head and neck pain conditions.

6610 Emphasizing the evaluation of autonomic dysfunctioncontributes to the diagnosis of ROHHAD Syndrome -- Based on a comparative analysis of two center ROHHAD Syndrome case reports and reported literature

Abstract Disclosure: Y. Wang: None. L. Chen: None. C. Gong: None. Background: ROHHAD is the acronym of rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysfunction, it is an extremely rare and potentially fatal disease.The purpose of this study is to describe the clinical symptoms and timelines of ROHHAD syndrome. Methods: All patients with ROHHAD syndrome were included. Patients from 2007 to2019 published previously was regarded as group 1. We searched for the keyword "ROHHAD" in the PUMBED database, and included all literature describing theclinical symptoms of ROHHAD patients (group 2, from October 2019 to August 2023).We compared and analyzed the above two sets of data with our data (group 3). Results: In the past 2 years, we diagnosed 16 cases of ROHHAD syndrome totally, with a male to female ratio of 8:8. Mean BMI z score was 4.23 ± 1.70, and the age of rapid obesity was 3.17 (1.67, 7.92) years old, ranging from 3 to 22.5 kg/year. The age at which hypoventilation, hypothalamic dysfunction, and autonomic dysfunction occurred was 5.55 (3.61, 8.25) years old, 4.46 (1.83, 9.25) years old, 3.42 (1.83, 8.00) years old, respectively. The most common autonomic dysfunction were cardiovascular manifestations (13 cases), thermal dysregulation and excessive sweating (each with 11 cases). Totally 13 cases had emotional, cognitive and behavioral abnormalities, 7 cases had neurogenic tumors. Case 2 had neurogenic tumors more than 5 years before rapid obesity, cognitive and behavioral abnormalities more than 2 years ago. Case 10 had abnormal pain sensation shortly after birth, and following polyuria in 2 years before rapid obesity. A total of 116 patients including 100 cases previously reported and 16 cases in this study were analyzed. Compared with the incidence rates of rapid obesity, central hypoventilation and hypothalamic dysfunction in patients in this study, there was no statistically significant difference between three groups. Among patients who had autonomic dysfunction (group 1 vs group 2 vs group 3), thermal dysregulation was 65.7% vs 17.0% vs 68.8%, cardiovascular manifestations was NA vs 12.8% vs 81.2%, excessive sweating was 28.6% vs 10.6% vs 68.8%, gastrointestinal disturbances was 11.4% vs 8.5% vs 62.5%, strabismus was 25.7% vs 12.8% vs 62.5%, and sleep disturbance was NA vs 6.4% vs 50.0%, all p< 0.05. The incidence of abnormal emotion, cognition and behavior was NA vs 29.8% vs 81.2% (p<0.05). Conclusion: The incidence of autonomic dysfunction in 16 patients of this study is100%, with multiple manifestations of autonomic dysfunction coexisting. The incidenceof autonomic dysfunction and abnormal emotion, cognition and behavior in reportedcases from different eras were significantly lower than those of our study, indicating theimportance of fully evaluating the autonomic dysfunction and limbic system. Fewpatients may occur tumors or autonomic dysfunction before rapid obesity. Presentation: 6/3/2024

Choice of Alternative Method of Surgical Intervention in Abdominal Rectus Diastasis with Concomitant Midline Hernias

INTRODUCTION: To date, no consensus has been achieved on the most appropriate surgical method for the treatment of abdominal rectus diastasis concomitant with midline hernias. AIM: Study of the results of three original methods of surgical treatment of patients with abdominal rectus diastasis concomitant with midline hernias. MATERIALS AND METHODS: The results of treatment of 74 patients have been analyzed. The patients were divided into three comparable groups: in the first group (n = 25), repair with local tissues with formation of aponeurotic duplication was performed, in the second group (n = 24), autodermal de-epithelialized graft was used, in the third group (n = 25) — mesh sub-lay implants. The following parameters were evaluated: duration of narcotic analgesia in the postoperative period, period of activation of patients, periods of inpatient treatment and results on Clavien-Dindo and EuraHSQoL scales. The follow-up period was from 1 to 10 years after surgery. RESULTS: The period of postoperative use of narcotic analgesics was 1.08 ± 0.38 days in the first group, 0.98 ± 0.33 days in the second group, 2.13 ± 0.93 days in the third group. The period of activation was 3.00 ± 1.53 days in the first group, 0.89 ± 0.36 days in the second group, 1.5 ± 0.48 days in the third group; the duration of inpatient treatment was 9.24 ± 1.88 bed-days, 6.34 ± 3.04 bed-days and 8.36 ± 2.14 bed-days, respectively. Postoperative complications in the first group were CDI class 6, CDII class 3, in the second group CDI class 1, in the third group CDI class 6, CDII class 3. At 12 months after the operation, painful sensations and functional discomfort on EuraHSQoL scale were absent in the second group, in the first and third groups, limitations in physical activity were noted (р ≤ 0.05; differences between the first and third groups were statistically insignificant, p ≥ 0.05). There were no statistically significant differences in the cosmetic discomfort between the groups (p ≥ 0.05). CONCLUSION: A safer and more effective method of repair of the anterior abdominal wall in patients with concomitant abdominal rectus diastasis and midline hernias is plastic surgery with application of de-epithelialized autodermal graft.

Five weeks of intermittent hand exposures to alternating cold and hot stimuli do not modify finger cold-induced vasodilatation response.

We tested the hypothesis that prolonged intermittent hand exposures to transient contrast thermal stimuli would enhance the finger cold-induced vasodilatation (CIVD) response during localized cooling. Eight healthy men participated in a 5-week regimen, during which they immersed, thrice per week, the non-dominant (EXP) hand in 8° and 43°C water, sequentially and at 3-min intervals, for a total period of 60min. The contralateral (i.e., dominant) hand served as the control (CON) hand. Before and after the regimen, subjects conducted two 30-min hand cold (8°C water) provocation trials, one with the EXP hand and the other with the CON hand. In addition, a flow-mediated dilatation test was performed in the brachial artery of the EXP arm. Regardless of the hand tested, the average finger skin temperature [CON hand: pre-trial=10.5 (1.2)°C, post-trial=10.8 (1.3)°C and EXP hand: pre-trial=10.7 (1.1)°C, post-trial 10.9 (1.1)°C; p=0.79], and the incidence of CIVD events [CON hand: pre-trial=1.1 (1.2) events, post-trial=1.2 (1.1) events and EXP hand: pre-trial=1.1 (0.8) events, post-trial=1.1 (0.8) events; p=0.88] were not affected by the 5-week regimen. The sensation of cold-induced pain was transiently alleviated following the regimen (p=0.02). The flow-mediated dilatation response of the EXP brachial artery remained unaltered [pre-trial=5.4 (3.2)%, post-trial=4.7 (3.6)%; p=0.51]. Therefore, five weeks of intermittent hand exposures to alternating cold and hot stimuli do not improve finger temperature responsiveness to sustained localized cold.

P2X4 receptor mediates macrophage infiltration leading to endometriotic cyst epithelium proliferation and hyperalgesia in mouse model

To evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells. Experimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses. The study was performed in academic and hospital research laboratories. NC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis. These results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.

Dual-functional core–shell microneedle patches for oral ulcers treatment

Microneedle patches have been widely used in transdermal drug delivery due to their painless and enhanced drug delivery. Despite their established success, their application within the oral cavity, characterized by a dense distribution of nociceptor, remains largely unexplored. Here, we introduce a well-designed dual-functional core–shell microneedle patches to address oral ulcers. The outer shell of the microneedle tips is crafted from hyaluronic acid (HA) and loaded with lidocaine, while the inner core, composed of gelatin methyl methacrylate (GelMA) encapsulates dexamethasone. The HA shell rapidly dissolves upon application, facilitating the immediate release of lidocaine to induce anesthesia at the ulcer site, thereby alleviating the associated painful sensations. Simultaneously, GelMA imparts mechanical strength and ensured the sustained release of dexamethasone. In vivo experiments further demonstrated that the Dex@MN group exhibiting the most rapid healing rate also displayed the highest levels of collagen deposition and the lowest concentrations of inflammatory factors. This collective evidence underscores the considerable potential of dual-functional core–shell microneedle patches in the treatment of oral diseases.

Neurovascular Shifts, Sensory Sensitivity, and PMDD in Autistic Women: Exploring Blood Flow Redirection, Mood Dysregulation, and Pain Tolerance during Menstruation

This article examines the relationship between Premenstrual Dysphoric Disorder (PMDD), neurovascular dynamics, and sensory sensitivities in autistic women during menstruation. The redirection of blood flow to the uterus during the menstrual cycle has been found to exacerbate cerebral perfusion deficits in neurodivergent individuals, particularly in the Prefrontal Cortex (PFC), which contributes to the mood dysregulation and emotional instability characteristic of PMDD. Autistic women, who often exhibit heightened sensory sensitivities, experience intensified discomfort during menstruation, as sensory overload and altered pain perception compound the emotional challenges of PMDD. These findings emphasize the need for neurodivergent-friendly menstrual products that mitigate both physical and emotional discomfort. Additionally, innovations using biodegradable materials, smart fabrics, and custom-fit menstrual solutions are discussed as potential breakthroughs to improve the quality of life for autistic women managing PMDD. This research highlights the importance of addressing both neurobiological and sensory aspects when designing interventions for PMDD in neurodivergent populations.

Comparing the Effect of Rosemary and Ketamine Gargles on Voice Hoarseness and Sore Throat After Tracheal Intubation

Background: This study compared the effects of rosemary and ketamine gargling on voice hoarseness and sore throat after tracheal intubation. Methods: This clinical trial was conducted on 116 patients who required general anesthesia and were randomly divided into intervention (30 drops of rosemary extract and 40mg of ketamine) and control (30 mL distilled water) groups using Randomize Allocation software. The measurement methods for obtaining information in the current study included the Visual Analogue Scale (VAS) for pain, GRBAS (Grade of Hoarseness; Roughness, Breathiness, Asthenia, and Strain), the auditory scale for the severity of voice hoarseness, and a questionnaire to evaluate the patient’s level of satisfaction. Then, the data was imported into SPSS V. 25 after data gathering. Results: The results revealed that patients of the three groups did not indicate significant hemodynamic changes, including the parameters systolic blood pressure (P = 0.73), diastolic blood pressure (P = 0.97), SpO2 level (P = 0.6), and heart rate (P = 0.31). However, the sore throat pain intensity of the rosemary group was significantly lower (P = 0.0008). The difference in time of the first pain sensation significantly differed among the three groups (P = 0.011). However, the mean pethidine administration of the control group (P = 0.003) was significantly higher, and the control group's satisfaction level (P = 0.02) was significantly lower. Conclusions: Gargling rosemary solution and ketamine did not affect the voice hoarseness after tracheal intubation, but the rosemary group had lower sore throat pain intensity.

In vitro and in vivo pharmacological evaluation of polygonum persicaria l.

The present study was designed to investigate the in vitro antioxidant, cytotoxic, anthelmintic and in vivo analgesic, anti-diarrheal, hypoglycemic and CNS anti-depressant properties of different solvent fractions of methanol extract of leaf and flower of Polygonum persicaria L., a notable medicinal plant in Bangladesh. The crude methanol extracts were partitioned separately to petroleum-ether, carbon tetrachloride, chloroform and aqueous fractions. In DPPH scavenging assay for antioxidant test, the aqueous fraction of flower extract showed maximum antioxidant activity with IC50 of 0.60 μg/ml. Most of the fractions revealed prominent lethality (LC50) against brine shrimp nauplii. The test samples also exhibited dose-dependent anthelmintic activity against Pheretima posthuma. The leaf extract and flower extract (200-and 400 mg/kg b.w.) can decrease the painful sensation in mice. Leaf extracts and flower extracts displayed 57.69 and 50% reduction of diarrhea induced by castor oil in mice, respectively. The plant samples exhibited hypoglycemic effect and CNS anti-depressant effect in mice. Based on the possibility of bioactivity, the plant can be thoroughly examined to determine its potential efficacy and to support its traditional uses. Bangladesh J. Bot. 53(3): 475-485, 2024 (September)

Qualitative somatosensory evaluation of recipient and donor sites of subepithelial connective tissue grafts: a preliminary study.

The subepithelial connective tissue graft (SCTG) plus coronal advanced flap is commonly evaluated by clinical parameters, but potential sensory changes (patients' perception of painful or painless sensations) need to be further explored. This preliminary study aimed to qualitatively evaluate the somatosensory profile of recipient and palatal donor sites of SCTG. Sensory tests were applied at SCTG recipient and donor sites at baseline, after 3 and 6 months. A single calibrated examiner applied Douleur Neuropathique 4 questionnaire (DN4), qualitative sensory test (QualST), discriminating the areas as hypersensitive, hyposensitive or normosensitive, and two-point acuity test. Descriptive statistics, non-parametric Kruskal Wallis test for QualST evaluation and ANOVA for Two-point test (p < 0.05) were used. QualST revealed that recipient areas presented no significant differences in tactile, pressure and thermal tests. Brush test revealed hyposensitivity after 3 months (p = 0.03). In donor areas, only thermal evaluation showed a significant difference (p = 0.01), being hypersensitive after 3 months and hyposensitive after 6 months. At baseline, all evaluations in recipient and donor areas were normosensitive. According to DN4, no patient reported pain in recipient and donor sites. Non-painful sensory perception was reported as numbness in recipient (3.14% of patients) and donor (18.4%) areas. No significant differences were found for two-point acuity test values. Somatosensory variations were observed in donor and recipient areas using qualitative tests, with no detection of painful sensations, only non-painful sensations of numbness and electric shock. This preliminary study demonstrated that alterations of hypo- and hypersensitivity may occur in donor and recipient areas of gingival grafts. However, when present, these alterations were non-painful and did not impact oral functions. ReBEC #RBR-7zz3b6p.

Специфика психических состояний осужденных женщин, содержащихся в местах лишения свободы с малолетними детьми

Introduction. The aim of the empirical study was to research the mental states of convicted women with young children. The study sample consisted of 153 convicted women with young children serving their sentences in a correctional institution. The study was conducted on the basis of the State Department of the Federal Penitentiary Service of Russia for the Kemerovo Region, the Federal Penitentiary Service of Russia for the Moscow Region, the Federal Penitentiary Service of Russia for the Vladimir Region, the Federal Penitentiary Service of Russia for the Republic of Mordovia. The scientific problem is to study the mental states of convicted women with young children. Research methods and techniques. The following set of methods was used to study mental states: ‘16-factor personality questionnaire - 16 PF’, form C (R. Kettell), “Depression scale” (A. Beck), clinical questionnaire for identification and assessment of neurotic states (K. K. Yakhin, D. M. Mendelevich), methodology for determining the dominant mental state “Dominant state” (L. V. Kulikov), questionnaire for studying the level of aggression (A. Bass and A. Darkey). The results of the conducted research were the identification of mental states of convicted women in prison with young children. It was established that negative mental states (tension, emotional instability, frustration, anxiety, irritation, depression, anxiety) prevail among these women.They are expressed fatigue, hysteria, vegetative disorders, which are manifested in unpleasant or painful somatic sensations. A high level of aggression and hostility has been diagnosed. The revealed negative mental states need timely psychological correction.

Immediate effects of thoracic mobilization versus soft tissue release on trunk motion, pain, and lumbar muscle activity in patients with chronic low back pain

IntroductionThoracic mobilization and tissue release are common manual techniques in clinical practice. However, the relative effects of these two treatments on chronic low back pain (CLBP) have not yet been explored. Thus, this study aimed to investigate and compare the immediate effects of thoracic mobilization with those of soft tissue release on trunk movement, pain sensation, and muscle activity in patients with CLBP. Methods28 participants were randomly assigned to two intervention groups. The mobilization group received mobilization treatment at the hypomobile joints of the trunk segment, while the soft tissue release group received thoracolumbar fascia release and massage in the lumbar region. The trunk range of motion (ROM), tissue hardness, pressure pain threshold (PPT), and erector spinae activity during light-weight lifting tasks were measured before and immediately after both interventions. FindingsAll measured outcomes in both groups improved after intervention (p < 0.05). The mobilization technique significantly improved side bending and rotation, PPT, and tissue hardness compared to soft tissue release. However, lumbar muscle activation reduced to a greater extent in the soft-tissue release group. ConclusionBoth techniques improved trunk ROM and PPT and reduced tissue hardness and muscle activation. Therefore, both these techniques are recommended for patients with CLBP. Trial registrationISRCTN75190733.

Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding

TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by Fanet al.“Structural basis of TRPV1 inhibition by SAF312 and cholesterol” sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.

PEMIJATAN TITIK LI-4 DAPAT MENGURANGI NYERI KANULASI ARTERIOVENOUSFISTULA PADA PASIEN CKD YANG MENJALANI HEMODIALISA: STUDI KASUS

Background, one of the vascular accesses used for hemodialysis is arteriovenous fistula. Arteriovenous fistula cannulation causes pain problems in patients. The cannulation procedure is felt as a painful sensation that needs to be treated, because the size of the needle used when cannulating an arteriovenous fistula is quite large compared to cannulating when installing an IV, namely 16 gauge. General purpose, to provide acute pain nursing care for Chronic Kidney Disease (CKD) patients undergoing hemodialysis in the hemodialysis room at RSU Aghisna Medika Kroya. Case collection method, pain scale measurement using a VAS instrument for 5 CKD patients undergoing hemodialysis without massage intervention and with massage intervention at the LI-4 point for 2 minutes or approximately 30-50 pressures. The results of nursing care, nursing care for acute pain in CKD patients undergoing hemodialysis after nursing for 1x4 hours with the application of massage at point LI-4 showed a decrease in the pain scale in patients without massage and with massage at point LI-4. In conclusion, LI-4 point massage therapy can be an therapeutic option to reduce the pain of arteriovenousfistula cannulation in CKD patients undergoing hemodialysis. Recommendation is hoped that more and larger case subjects will be taken in the next research so that the results will be more effective.

Navigating the Controversies: Role of TRPM Channels in Pain States.

Chronic pain is a debilitating condition that affects up to 1.5 billion people worldwide and bears a tremendous socioeconomic burden. The success of pain medicine relies on our understanding of the type of pain experienced by patients and the mechanisms that give rise to it. Ion channels are among the key targets for pharmacological intervention in chronic pain conditions. Therefore, it is important to understand how changes in channel properties, trafficking, and molecular interactions contribute to pain sensation. In this review, we discuss studies that have demonstrated the involvement of transient receptor potential M2, M3, and M8 channels in pain generation and transduction, as well as the controversies surrounding these findings.

Learned symptom-specific fear towards a visceral sensation and its impact on perceptual habituation.

Impaired habituation of bodily sensations has been suggested as a contributing factor to chronic pain. We examined in healthy volunteers the influence of fear learning towards a non-painful sensation in the esophagus on the perceptual habituation of this sensation. In a homoreflexive fear learning paradigm, non-painful electrical sensations in the esophagus were used as a conditioned stimulus (CS). This sensation was presented 42 times before, during, and after fear learning. In the fear learning group (n = 41), the CS was paired with a painful electrical sensation in the esophagus (unconditioned stimulus; US). In the control group (n = 41), the CS was not paired with the US. Ratings for CS intensity, US expectancy, startle electromyogram (EMG), skin conductance responses (SCR) and event-related potentials (ERPs) to the CS were assessed. Compared to the control group, fear learning was observed in the fear learning group as evidenced by potentiated startle responses after the CS relative to ITI (t(1327) = 3.231, p = .001) and higher US expectancy ratings (t(196) = 3.17, p = .002). SCRs did not differ between groups (F1, 817 = 1.241, p = .33). Despite successful fear learning, the fear learning group did not show a distinct pattern of habituation to the visceral CS relative to the control group (intensity ratings: F1, 77.731 = 0.532 p = .47; ERPs: F1, 520.78 = 0.059, p = .94). Acquired fear to non-painful esophageal sensations does not affect their perceptual habituation patterns.

Supraclavicular versus infraclavicular brachial plexus block in upper limb orthopaedic surgery: a systematic review and meta-analysis of randomised controlled trials.

Clavicular brachial plexus blocks are a popular method to provide analgesia in upper limb surgery. Two common approaches include the infraclavicular (IC) and supraclavicular (SC) blocks. These two techniques have been compared previously; however, it is still being determined from the current literature whether one should be favoured. A search was performed on the following databases: Ovid Medline, EMBASE and the Web of Science from inception until 30.04.2023. All RCTs comparing SC and IC approaches in upper limb orthopaedic surgery were included. The primary outcome was block success rate. Eighteen RCTs comprising 1389 patients were included. The success rate of IC blocks was higher than SC blocks, odds ratio 0.61 (95% CI 0.41-0.91, p = 0.01). A small number of studies reported on secondary outcomes. A reduced rate of Horner's syndrome was observed in the IC group. Otherwise, no difference was noted between the approaches in terms of procedure time, sensory onset time, patient satisfaction, pain and vascular puncture. IC blocks demonstrate a higher success rate over SC blocks. Across all studies a large variance in outcome reporting and definitions was observed. Future studies should conform to an agreed definition set to facilitate comparison.