Somatic Nerve Research Articles

Nerve-sparing surgery for deep lateral parametrial endometriosis

Although dLPE is not overly rare, isolation of the autonomic nerves from dLPE cannot always be guaranteed. In patients with endometriosis lesions that are embedded in the deep parametrium, nerve-sparing techniques are no longer considered feasible, except for those with unilateral involvement. However, even one-sided radical parametrectomy may actually lead to bladder dysfunction, which seriously affects the quality of life. Therefore, the objective is to demonstrate the anatomical and technical highlights of nerve-sparing laparoscopic surgery for deep lateral parametrial endometriosis (dLPE). Stepwise demonstration of this method with a narrated video footage. An urban general hospital. A 38-year-old woman, para 1, presented with a 5-year history of severe chronic pelvic and gluteal pain, all of which were resistant to pharmacotherapy. The patient showed no neurological disorders, such as bladder dysfunction. Magnetic resonance imaging revealed right ovarian endometrioma and hydrosalpinx with dLPE reaching the lateral pelvic wall. Based on the dermatome involved, we suspected that the main lesion causing gluteal pain was located around the second and third sacral roots. Laparoscopic excision of dLPE with a pelvic autonomic nerve-sparing technique, decompression of somatic nerves and preservation of all branches of the internal iliac vessels. Assessment of preserved tissue perfusion using indocyanine green. The procedure was performed using 8 steps, as follows: step 1, adhesiolysis and adnexal surgery; step 2, complete ureterolysis; step 3, identification and dissection of the hypogastric nerve and inferior hypogastric plexus with development of the pararectal space; step 4, dissection of the internal iliac vessels; step 5, identification and dissection of the sacral roots S2-S4 and the pelvic splanchnic nerves; step 6, complete removal of dLPE; step 7, hemostasis and assessment of tissue perfusion using indocyanine green; and step 8, application of barrier agents to prevent adhesion. Dissection of the pelvic nerves before dLPE excision revealed the relationship between the lesions and pelvic innervation, thereby reducing the risk of nerve injury, whether by minimizing the risk of neuropraxia or by allowing as many nerve fibers as possible to be spared in patients with some invasion of the pelvic nerve system. We considered even partial preservation of these nerves as beneficial to the resumption of pelvic organ functions. The step-by-step technique should help perform each stage of the surgery in a logical sequence, ensuring easy and safe completion of the procedure. Relief from severe pain, avoidance of postoperative morbidity (including intermittent self-catheterization). The patient developed no perioperative complications, including postoperative bladder, rectal, or sexual dysfunctions. Pain was completely resolved. Nerve-sparing surgery is technically safe and feasible for selected patients with dLPE. Suitably tailored treatment should be provided for each individual based on both latest scientific evidence and life planning for the patient.

Peripheral neurostimulation for encoding artificial somatosensations.

The direct neural stimulation of peripheral or central nervous systems has been shown as an effective tool to treat neurological conditions. The electrical activation of the nervous sensory pathway can be adopted to restore the artificial sense of touch and proprioception in people suffering from sensory-motor disorders. The modulation of the neural stimulation parameters has a direct effect on the electrically induced sensations, both when targeting the somatosensory cortex and the peripheral somatic nerves. The properties of the artificial sensations perceived, as their location, quality and intensity are strongly dependent on the direct modulation of pulse width, amplitude and frequency of the neural stimulation. Different sensory encoding schemes have been tested in patients showing distinct effects and outcomes according to their impact on the neural activation. Here, I reported the most adopted neural stimulation strategies to artificially encode somatosensation into the peripheral nervous system. The real-time implementation of these strategies in bionic devices is crucial to exploit the artificial sensory feedback in prosthetics. Thus, neural stimulation becomes a tool to directly communicate with the human nervous system. Given the importance of adding artificial sensory information to neuroprosthetic devices to improve their control and functionality, the choice of an optimal neural stimulation paradigm could increase the impact of prosthetic devices on the quality of life of people with sensorimotor disabilities.

The Effect of the Port Numbers Used in Video-assisted Thoracoscopic Surgery on the Success of Ultrasound-Guided Erector Spinae Plane Block; A Single Center Retrospective Study

Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure with lower pain scores and less morbidity than thoracotomy. However, it is necessary to provide adequate pain control in VATS. For this purpose, blocking visceral and somatic nerve fibers results in successful pain management. This retrospective study evaluated the effect of using different numbers of ports on the success of erector spinae plane block (ESPB) for postoperative analgesia management in patients undergoing VATS. We conducted a retrospective, single-center study between Sep 2020 and Aug 2021. According to the number of ports used, fifty-eight patients were assigned to three groups (single port, dual port, and three-port). Preoperative ultrasound-guided ESPB was performed on all patients. The primary outcome was the numerical rating scale (NRS) score assessed for pain severity at different periods after surgery. The secondary outcome was the postoperative cumulative opioid consumption, and the exploratory outcomes were to determine the length of hospital stay and the incidence of opioid-related side effects. Static and dynamic NRS scores were significantly higher in the three-port group in the first 12-hour postoperative period after admission to the post-anesthesia care unit (p<0.05). After the first 12-hour period after surgery, static and dynamic NRS scores did not differ significantly between the groups (p=0.158 and p=0.125, respectively). Cumulative opioid consumption in the first 24 hours postoperatively was considerably higher in the three-port group than in the other groups (33.04±21.35 mg, p=0.001). Rescue analgesia consumption was similar between all groups (p=0.341). Preoperative single-shot ESPB injection may be associated with better analgesia and less opioid consumption in the first 12 hours postoperatively in patients undergoing single or two-port VATS compared to the multi-port technique.

Umbilical Cord Mesenchymal Stem Cells Promoting Spinal Cord Injury Repair Visually Monitored by AIE‐Tat Nanoparticles

AbstractSpinal cord injury (SCI) is a severe body trauma that can cause permanent loss of somatic nerve function and lacks effective treatment. Transplantation of stem cells is a promising therapeutic approach for SCI but faces with the difficulty of long‐term tracking of stem cells in vivo precisely. Herein, this work wishes to report a kind of umbilical cord mesenchymal stem cells (UC‐MSCs) labeled with aggregation‐induced emission (AIE)‐Tat nanoparticles (NPs) for tracing the repair and treatment of SCI. These AIE‐Tat NPs have strong fluorescence, good biocompatibility, and long‐term tracking ability with a high signal‐noise ratio. The labeling of AIE‐Tat NPs does not induce adverse effects on the activity and performance of UC‐MSCs. The fluorescence signal of the UC‐MSCs can be monitored for up to 28 days, reflecting the viability, colonization, and function of the transplanted UC‐MSCs. The transplantation of UC‐MSCs can secrete nerve growth factors and maintain the viability of cells in the highly reactive oxygen species microenvironment, leading to effective recovery of injured spinal cord, which is further confirmed by the behavioral rehabilitation and histopathological results. These findings demonstrate that long‐term tracking of UC‐MSCs labeled with AIE‐Tat NPs is a promising method to monitor stem cell transplantation therapy for SCI.

Physiology of the Vagus Nerve: Basic Medical Research from the Past to the Present

The vagus nerve, which is the 10th cranial nerve, exits from the medulla and distributes widely to the visceral organs. Although it contains the motor, somatic, and sympathetic nerves, the main component is the parasympathetic nerve, which acts as the core of homeostasis. The vagal efferent regulates the cardiac muscle, striated muscle and glands, while the vagal afferent sends the information from the visceral organs to the brain. The vagus nerve is also responsible for the gut-brain axis.

Аpplication of massage for traumatic injuries of the upper limbs in participants of combat

The scientific work is devoted to the development and substantiation of the technique of deep reflex muscle massage (DRMM) to restore the function of the shoulder joint in traumatic injuries of the upper extremity participants in combatants. The results of the analysis of sources of information, scientific researches and practical experience of authors concerning urgency of a problem and application of DRMM at 250 persons with limitations of function of a shoulder joint of various genesis are generalized. The main distinctive features of the proposed DRMM are the application of the site and the method of massage. The procedure plan (except for the neck area and the girdle of the upper extremities) includes massage of the lumbar region, thorough massage of the spine and vertebral areas. The method of massage involved differentiated massage of the muscles that provide the function of the shoulder joint: the muscles that lead the shoulder - by a soothing (relaxing) method, that lead the shoulder – by a tonic. Both superficial and deep-seated muscle fibers of these muscles, along their entire length, were thoroughly massaged. Mandatory massage was the place of attachment of all the muscles that lead the shoulder by the braking method. Round muscles, the biologically active point of Xin-she, were also thoroughly massaged. The authors' research has shown that DRMM accelerates bone regeneration, normalizes the functional state of the musculoskeletal system, somatic and autonomic nervous systems, psychoemotional state, physical performance. DRMM makes it possible to reduce the number of complications, physical defects, prevent (reduce) stiffness of the joints, increase the chances of preventing the disability of defenders of Ukraine.

The erector spinae block: a novel approach to pain management in acute appendicitis

BackgroundAcute abdominal pain is one of the most common complaints that patients present with in the emergency room and has long been a challenge to effectively manage without relying on opioid analgesia. The use of ultrasound-guided peripheral nerve blocks (UGRA) represents a new frontier in multimodal pain control regimens in the acute setting. An erector spinae plane (ESP) block is believed to mediate pain relief in multiple dermatomes through blockage of both visceral and somatic nerves. Analgesia provided by a single injection can help keep a patient comfortable for hours without breakthrough pain and the subsequent need for frequent redosing of opioid pain medication. To this date, there is very limited evidence of an ESP block in the utilization of acute appendicitis in the emergency department.Case reportThis case report presents a 26-year-old female with a past medical history of polycystic ovarian syndrome (PCOS) and a tubal ligation that presented with 7/10 right lower quadrant abdominal pain that began 1 h prior to arrival. She stated that she felt like this was similar to her PCOS exacerbations in the past. During her evaluation, she underwent a computed tomography (CT) scan of her abdomen and pelvis that was remarkable for acute, uncomplicated appendicitis. She was given 4 mg of morphine for her pain with little response, so the offer was made for an erector spinae block that the patient elected to receive. After being consented both for the procedure and for research, she received a right-sided erector spinae block with 20 mL’s of 0.2% ropivacaine (2 mg/mL) at the L1 vertebral level. After approximately 15 min, she stated that she had a reduction in her pain from a 6/10 to a 1/10 that persisted throughout the rest of her stay in the emergency department.

In vivo peripheral nerve activation using sinusoidal low-frequency alternating currents.

The sinusoidal low-frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In-silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering-Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. Experiments were conducted in isoflurane-anesthetized swine (n=5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex-induced reduction in the breathing rate. LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency-dependent. The HB threshold was 1.02 ± 0.3 mAp at 5Hz, 0.66 ± 0.3 mAp at 10Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 μs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim-based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field.

Effect of Ropivacaine Combined with Small Doses of Triamcinolone and Continuous Nerve Block of Unilateral Paravertebral Canal Guided by Ultrasound on Metastasis after Radical Treatment of Lung Cancer

Continuous nerve block of unilateral paravertebral canal is one of the most reliable and the most commonly performed techniques to control intra- and postoperative pain. It is the technique of injecting local anaesthetic alongside the thoracic vertebra close to where the spinal nerves emerge from the intervertebral foramen. This produces unilateral, segmental, somatic, and sympathetic nerve blockade, which is effective for anaesthesia and in treating acute and chronic pain of unilateral origin from the chest and abdomen. Ultrasound guidance with or without nerve stimulator has reduced the amount of local anaesthetics (LA) to achieve a successful block, which may minimize complications of continuous nerve block of unilateral paravertebral canal. Previous studies have suggested that continuous nerve block of unilateral paravertebral canal with ropivacaine combined with small doses of triamcinolone was effective to achieve sensory and motor block after lung cancer surgery. Previous studies have used a fixed large dose in different volumes and concentrations for a nerve block, infraclavicular block, axillary block, and humeral canal block. The results of these studies with the respects of onset time, successful rate, and block duration were not consistent. Various factors, including the technique used, the anatomic aspects of the injection, and the pharmacodynamics aspect of drug, may influence the results. We tested the hypothesis that 50,25,10 mg ropivacaine and 50,25,10 mg triamcinolone of three combinations of volumes and concentrations for ultrasound-guided continuous nerve block of unilateral paravertebral canal produce different effects in the aspect of survival rate. Here, the drug effect was analyzed using the cross cluster K-nearest neighbors (KNN). The whole experimentation was carried out under MATLAB environment.

Distribution of Kudoa thyrsites (Cnidaria, Myxozoa) myoliquefactive stages in Northeast Atlantic mackerel (Scomber scombrus) inferred from qPCR and histology

Kudoa thyrsites is a myxosporean parasite (Cnidaria, Myxozoa) that infects the skeletal and cardiac muscle of Northeast Atlantic (NEA) mackerel (Scomber scombrus). Heavy infections are associated with post-mortem myoliquefaction of the host skeletal muscle which reduces the quality of the fish product. The biological infection characteristics of the parasite in NEA mackerel are poorly known. This study examined the distribution of K. thyrsites in various organs of NEA mackerel from the northern North Sea, and elucidates the relationship between density of infection, developmental stage and parasite distribution in the musculature, and the extent of visible flesh myoliquefaction. Quantitative polymerase chain reaction (qPCR) data showed that K. thyrsites is unevenly distributed in the somatic musculature of the fish host, with highest density in the anterior ventral muscle sections—the belly flaps. A weak positive correlation was observed between the level of myoliquefaction and the parasite density in the fish host muscle. This relationship was also reflected by the amount and distribution of parasite developmental stages seen during histological examinations. Histological findings indicate an association between the dispersion of free myxospores and the level of myoliquefaction of the fish host muscle. Visceral organs were also found infected using qPCR, although at lower densities compared to the musculature.

Neurogenic Bladder Physiology, Pathogenesis, and Management after Spinal Cord Injury.

Urinary incontinence is common after spinal cord injury (SCI) due to loss of supraspinal coordination and unabated reflexes in both autonomic and somatic nervous systems; if unchecked, these disturbances can become life-threatening. This manuscript will review normal anatomy and physiology of the urinary system and discuss pathophysiology secondary to SCI. This includes a discussion of autonomic dysreflexia, as well as its diagnosis and management. The kidneys and the ureters, representing the upper urinary tract system, can be at risk related to dyssynergy between the urethral sphincters and high pressures that lead to potential vesicoureteral reflux, urinary tract infections, and calculi associated with neurogenic lower urinary tract dysfunction (NLUTD). Recent guidelines for diagnosis, evaluation, treatment and follow up of the neurogenic bladder will be reviewed and options provided for risk stratification and management. Mechanical, pharmacological, neurolysis and surgical management will be discussed.

459-P: Effects of Liraglutide on Somatic Nerve Function in Subjects with Type 2 Diabetes

Background: Preclinical data has shown that GLP-1 receptor agonists play a role in nerve regeneration and repair. However, few studies have investigated the effects of these compounds on nerve function in humans. The aim of this study was to examine the effect of Liraglutide (Lira) on somatic nerve function in patients with type 2 diabetes. Methods: Randomized, double-blind, placebo-controlled study of Lira 1.8 mg daily for 52 weeks. All participants were evaluated with the following somatic nerve function tests: Utah Early Neuropathy Scale (UENS) , quantitative sensory testing (QST) for cold and warm perception thresholds (Q-Sense v6.0.13.1; Medoc - Minneapolis, MN) , nerve conduction studies (NCS) (Sierra Summit System; Cadwell Industries - Kennewick, WA) and in vivo corneal confocal microscopy (CCM) to measure corneal nerve fiber density, branching and length (Tomograph III; Heidelberg Engineering - Smithfield, Rhode Island) Results: We randomized 44 subjects (21 to Lira and 23 to pb) . Baseline characteristics were similar. Main results are shown in Table 1. In both groups, there was no significant change on UENS, QSTs, NCS and CCM measures after 1 year of treatment. The results also were not significantly different between the groups. Conclusions: This study did not show improvements in somatic nerve function after 52 weeks of treatment with Lira. The small sample size may have contributed to the negative result. Disclosure C.M.Casellini: Advisory Panel; Nevro Corp. H.Parson: None. M.D.Bailey: None. E.S.Siraj: Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk. Funding Novo Nordisk (Grant#15-12-FB-0218)

Neurodynamic Treatment Promotes Mechanical Pain Modulation in Sensory Neurons and Nerve Regeneration in Rats

Background: Somatic nerve injuries are a rising problem leading to disability associated with neuropathic pain commonly reported as mechanical allodynia (MA) and hyperalgesia. These symptoms are strongly dependent on specific processes in the dorsal root ganglia (DRG). Neurodynamic treatment (NDT), consisting of selective uniaxial nerve repeated tension protocols, effectively reduces pain and disability in neuropathic pain patients even though the biological mechanisms remain poorly characterized. We aimed to define, both in vivo and ex vivo, how NDT could promote nerve regeneration and modulate some processes in the DRG linked to MA and hyperalgesia. Methods: We examined in Wistar rats, after unilateral median and ulnar nerve crush, the therapeutic effects of NDT and the possible protective effects of NDT administered for 10 days before the injury. We adopted an ex vivo model of DRG organotypic explant subjected to NDT to explore the selective effects on DRG cells. Results: Behavioural tests, morphological and morphometrical analyses, and gene and protein expression analyses were performed, and these tests revealed that NDT promotes nerve regeneration processes, speeds up sensory motor recovery, and modulates mechanical pain by affecting, in the DRG, the expression of TACAN, a mechanosensitive receptor shared between humans and rats responsible for MA and hyperalgesia. The ex vivo experiments have shown that NDT increases neurite regrowth and confirmed the modulation of TACAN. Conclusions: The results obtained in this study on the biological and molecular mechanisms induced by NDT will allow the exploration, in future clinical trials, of its efficacy in different conditions of neuropathic pain.

Changes in Postural Control Ability after Wearing Corrective Glasses for Distance in Older Adults and Their Causes.

Deterioration of postural control in older adults is unavoidable due to age-associated degeneration of the visual system. Our study objective was therefore to verify whether there is a positive effect on postural control ability after providing older adults, whose postural control function had deteriorated, with corrective glasses to correct refractive errors. Twenty-seven participants, 66 to 90 years of age, were included in this study. Stability index, synchronization index, and sway power index were measured by using the TETRAX balance system and comparatively analyzed before and after wearing the corrective glasses for distance. The stability index after wearing corrective glasses significantly decreased compared to before wearing them (p < 0.05). Four synchronization areas, among six, showed a significant increase in the synchronization index after wearing corrective glasses compared to before wearing them (p < 0.05). The sway power index significantly decreased in the mid–high and the high frequency after wearing the corrective glasses (p < 0.05). Optimal visual information can be obtained through the correction of residual refractive errors, eliciting a positive effect on the overall posture control by improving the sensory integration ability with the somatic nervous system responsible for posture control, maximizing the lower extremity motor function of the elderly.

Dietary Use of the Microalga Chlorella fusca Improves Growth, Metabolism, and Digestive Functionality in Thick-Lipped Grey Mullet (Chelon labrosus, Risso 1827) Juveniles

In recent years, a clear emphasis has been placed on replacing fishmeal and fish oil in aquafeeds with other alternative ingredients, including algae, particularly in low trophic omnivorous fish species. This work aimed at evaluating the effects of moderate dietary supplementation with the green microalga Chlorella fusca on growth, metabolism, and digestive functionality in juvenile thick-lipped grey mullet (Chelon labrosus). Fish were fed a control diet (CT) or a diet containing 15% C. fusca (C-15) biomass during 90 days. C. labrosus fed with the C-15 diet showed higher growth performance (in terms of final weight and length, weight gain, and specific growth rate) than the control group. Somatic indices and muscle proximate composition were similar at the end of the feeding trial. Regarding fatty acids profile, C. fusca-fed fish showed a selective retention of docosahexaenoic acid (DHA) in the liver, and arachidonic acid (ARA), eicosapentaenoic acid (EPA), and DHA in the muscle. Dietary inclusion of this microalga significantly increased intestinal total alkaline protease, leucine aminopeptidase, and alkaline phosphatase activities in specimens fed with C-15 diet. Furthermore, intestine histological analysis revealed the absence of damage signs on gut morphology in fish fed the microalgae supplemented diet. Thick-lipped grey mullets fed the C-15 diet increased plasma glucose and decreased plasma lactate. Overall, the effects observed on liver (lipid metabolism, glycolysis and glycogenolysis) enzyme activities, together with adequate fatty acid profile, metabolic response, and gut morphology, and a significant increase in the intestinal mucosa’s digestive and absorptive capacity, could explain the positive effects on growth performance obtained in fish fed the microalgae-supplemented diet. In conclusion, the results obtained showed that C. fusca is suitable as dietary ingredient for feeding thick-lipped grey mullet juveniles.

Combination of electroacupuncture and pharmacological treatment improves insulin resistance in women with polycystic ovary syndrome: Double-blind randomized clinical trial.

BackgroundAcupuncture is a nonpharmacological treatment which has been known to improve ovulatory function in polycystic ovary syndrome (PCOS) women. Acupuncture modulates the somatic and autonomic nervous systems, which regulate endocrine and metabolic functions to impact ovulatory functions.ObjectiveTo investigate the effectiveness of electroacupuncture (EA) and pharmacological combination therapy on improving insulin resistance in women with PCOS.Materials and MethodsThis double-blind, randomized clinical trial was performed on 44 participants from March to September 2018 at Cipto Mangunkusumo National hospital, Jakarta, Indonesia. Participants were randomly allocated to treatment (true EA + medication) and control group (sham EA + medication) in a 1:1 ratio using a web-based computer random-number generator. Randomization was carried out by an independent project manager. Both groups received 12 sessions of acupuncture therapy and metformin as pharmacological therapy.ResultsThis study showed a significant decrease in the Homeostatic Model Assessment for Insulin Resistance index in the true EA + medication group before and after therapy (p = 0.014).ConclusionThe combination of EA and pharmacological therapy effectively improves insulin sensitivity in women with PCOS.

Involvement of GABAA-rho Receptor in a Trigeminal Neuralgia Model

The antiepileptic drug carbamazepine is effective in a subpopulation of trigeminal neuralgia patients, in particular those suffering from pain associated with vascular compression of a trigeminal nerve. However, carbamazepine has failed in clinical trials for other neuropathic pain conditions, even those associated with peripheral nerve compression injuries. Carbamazepine is both a GABAA receptor (GAR) agonist and a blocker of voltage-gated Na+ channels (VGSC), and our recent data suggest that differences between trigeminal and somatic nerves with respect to the VGSC present are not sufficient to account for the therapeutic selectivity of carbamazepine. Therefore, we hypothesized that these observations reflected a differential involvement of GARs in somatic and trigeminal nerves. To test this, we employed a combination of electrophysiological and behavioral experiments in rat models of somatic (sciatic nerve, SN) and trigeminal (infraorbital nerve, ION) nerve compression (CCI). We observed that the potency of carbamazepine-induced compound action potential (CAP) block was increased by CCI of the ION but not the SN, and this increase in potency was reduced by the GAR blocker picrotoxin. The potency of the GAR agonist muscimol-induced block of the ION was greater than the SN, and CCI produced a further increase in efficacy. The GABAA-rho subunit mRNA and protein was increased by CCI of the ION, but not SN. The GABAA-rho receptor selective antagonist TPMPA reduced carbamazepine-induced CAP block of the ION. CCI was also associated with an increase in the potency of the GABAA-rho receptor preferring agonist TACA-induced block of the ION, but not SN. Finally, local administration of TACA to the ION but not SN, dose-dependently reversed CCI-induced mechanical sensitivity. Taken altogether, our results suggest GABAA-rho receptors are present and functional in ION, but not SN. This differential distribution of GABAA receptors could account for the therapeutic selectivity of carbamazepine for the treatment of TN. The work was supported by generous donations from TN patients and family members as well as NIH grant R01NS064988.

A vestibular examination must include the 12:00 region

ABSTRACT Introduction The vestibule is an endodermal tissue located on the skin surface between Hart's line at the inner aspect of the labia minora (ectoderm), and the hymen, at the vaginal opening (mesoderm). The vestibule contains the urethral meatus and minor and major vestibular glands. The vestibule releases mucinous lubrication during sexual arousal that is achieved, in part, by vestibular innervation, likely from somatic (pudendal branch) and autonomic (pelvic branch) nerves. As part of an evaluation of patients with entrance dyspareunia, providers should perform a cotton-tip swab test to assess pain intensity and degree of erythema. Typically, the locations assessed are the 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations of the posterior and right/left anterior vestibule. This testing strategy, however, does not include the entire vestibule. The 12:00 region of the vestibule is located above the urethral meatus, just below the clitoris and medial to Hart's line. The 12:00 region can also be painful during cotton-tip swab testing. Few providers examine this region or consider it during treatment. Objective The main objective of this study was to compare the pain scores of cotton-tip swab testing and degree of erythema of the 12:00 region to those of the 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations in women presenting with entrance dyspareunia. The secondary objective was to examine the 12:00 region for the presence of minor vestibular glands. Methods Women presenting to our clinic with complaints of entrance dyspareunia underwent vulvoscopy with photography and cotton-tip swab testing including the 12:00 region while using a vulvoscope (Wallach Zoomscope) with attached camera (Cannon). Pain intensity was rated by the patient (0 – 10), with pain &amp;gt;3 considered clinically significant. Erythema was rated by the provider (absent, mild, moderate or severe) with any erythema considered clinically significant. Results A total of 144 women (mean age 43 +/- 20, range 13-83 years) underwent vulvoscopy at the standard 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations. In addition, they were tested concomitantly at the 12:00 location. Among this group of women, 26 (18%) had absent pain and absent erythema throughout all locations; 25 (18%) had positive findings of pain and erythema in at least 3 of the usual vestibular locations but not at 12:00; and 92 (64%) had pain and erythema in at least 1 of the usual vestibular locations and at 12:00. Photographs revealed 27% of those experiencing pain at the 12:00 had obvious single/multiple ostia of minor vestibular glands at that location. Conclusions Women with entrance dyspareunia commonly have pain and erythema at the 12:00 region of the vestibule. Photography reveals the presence of minor vestibular glands at the 12:00 location. Providers should examine the entire vestibule including the 12:00 region during examination. Providers should consider including the 12:00 vestibule when treating entrance dyspareunia with medication such as compounded testosterone and estradiol and/or surgery. Disclosure Work supported by industry: no.

The 12:00 Region of the Vestibule: Often Overlooked during Examination and Treatment of Women with Entrance Dyspareunia

ABSTRACT Introduction The vestibule is an endodermal tissue located on the skin surface between Hart's line at the inner aspect of the labia minora (ectoderm), and the hymen, at the vaginal opening (mesoderm). The vestibule contains the urethral meatus and minor and major vestibular glands. The vestibule releases mucinous lubrication during sexual arousal that is achieved, in part, by vestibular innervation, likely from somatic (pudendal branch) and autonomic (pelvic branch) nerves. As part of an evaluation of patients with entrance dyspareunia, providers should perform a cotton-tip swab test to assess pain intensity and degree of erythema. Typically, the locations assessed are the 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations of the posterior and right/left anterior vestibule. This testing strategy, however, does not include the entire vestibule. The 12:00 region of the vestibule is located above the urethral meatus, just below the clitoris and medial to Hart's line. The 12:00 region can also be painful during cotton-tip swab testing. Few providers examine this region or consider it during treatment. Objective The main objective of this study was to compare the pain scores of cotton-tip swab testing and degree of erythema of the 12:00 region to those of the 1:00, 3:00, 5:00, 6:00, 7:00, 9:00 and 11:00 locations in women presenting with entrance dyspareunia. The secondary objective was to examine the 12:00 region for the presence of minor vestibular glands. Methods Women presenting to our clinic with complaints of entrance dyspareunia underwent vulvoscopy with photography and cotton-tip swab testing including the 12:00 region while using a vulvoscope (Wallach Zoomscope) with attached camera (Cannon). Pain intensity was rated by the patient (0 – 10), with pain &amp;gt;3 considered clinically significant. Erythema was rated by the provider (absent, mild, moderate or severe) with any erythema considered clinically significant. Results A total of 144 women (mean age 43 +/- 20, range 13-83 years) underwent vulvoscopy at the standard 1:00, 3:00, 5:00, 6: 00, 7:00, 9:00 and 11:00 locations. In addition, they were tested concomitantly at the 12:00 location. Among this group of women, 26 (18%) had absent pain and absent erythema throughout all locations; 25 (18%) had positive findings of pain and erythema in at least 3 of the usual vestibular locations but not at 12:00; and 92 (64%) had pain and erythema in at least 1 of the usual vestibular locations and at 12:00. Photographs revealed 27% of those experiencing pain at the 12:00 had obvious single/multiple ostia of minor vestibular glands at that location. Conclusions Women with entrance dyspareunia commonly have pain and erythema at the 12:00 region of the vestibule. Photography reveals the presence of minor vestibular glands at the 12:00 location. Providers should examine the entire vestibule including the 12:00 region during examination. Providers should consider including the 12:00 vestibule when treating entrance dyspareunia with medication such as compounded testosterone and estradiol and/or surgery. Disclosure No

High-intensity interval training for 12 weeks improves cardiovascular autonomic function but not somatosensory nerve function and structure in overweight men with type 2 diabetes

Aims/hypothesisIt remains unclear whether and which modality of exercise training as a component of lifestyle intervention may exert favourable effects on somatosensory and autonomic nerve tests in people with type 2 diabetes.MethodsCardiovascular autonomic and somatosensory nerve function as well as intraepidermal nerve fibre density (IENFD) were assessed in overweight men with type 2 diabetes (type 2 diabetes, n = 20) and male glucose-tolerant individuals (normal glucose tolerance [NGT], n = 23), comparable in age and BMI and serving as a control group, before and after a supervised high-intensity interval training (HIIT) intervention programme over 12 weeks. Study endpoints included clinical scores, nerve conduction studies, quantitative sensory testing, IENFD, heart rate variability, postural change in systolic blood pressure and spontaneous baroreflex sensitivity (BRS).ResultsAfter 12 weeks of HIIT, resting heart rate decreased in both groups ([mean ± SD] baseline/12 weeks: NGT: 65.1 ± 8.2/60.2 ± 9.0 beats per min; type 2 diabetes: 68.8 ± 10.1/63.4 ± 7.8 beats per min), while three BRS indices increased (sequence analysis BRS: 8.82 ± 4.89/14.6 ± 11.7 ms2/mmHg; positive sequences BRS: 7.19 ± 5.43/15.4 ± 15.9 ms2/mmHg; negative sequences BRS: 12.8 ± 5.4/14.6 ± 8.7 ms2/mmHg) and postural change in systolic blood pressure decreased (−13.9 ± 11.6/−9.35 ± 9.76 mmHg) in participants with type 2 diabetes, and two heart rate variability indices increased in the NGT group (standard deviation of R–R intervals: 36.1 ± 11.8/55.3 ± 41.3 ms; coefficient of R–R interval variation: 3.84 ± 1.21/5.17 ± 3.28) (all p<0.05). In contrast, BMI, clinical scores, nerve conduction studies, quantitative sensory testing, IENFD and the prevalence rates of diabetic sensorimotor polyneuropathy and cardiovascular autonomic neuropathy remained unchanged in both groups. In the entire cohort, correlations between the changes in two BRS indices and changes in dot{V}{mathrm{O}}_{2max } over 12 weeks of HIIT (e.g. sequence analysis BRS: r = 0.528, p=0.017) were observed.Conclusions/interpretationIn male overweight individuals with type 2 diabetes, BRS, resting heart rate and orthostatic blood pressure regulation improved in the absence of weight loss after 12 weeks of supervised HIIT. Since no favourable effects on somatic nerve function and structure were observed, cardiovascular autonomic function appears to be more amenable to this short-term intervention, possibly due to improved cardiorespiratory fitness.Graphical abstract