Branch Of Sciatic Nerve Research Articles

The Exploratory Study of the PTEN-AKT/mTOR Signaling Pathway in the Corresponding Dorsal Root Ganglion during Compensatory Repair via Small Gap Amplification in Sciatic Nerve Injury.

Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.

Biomimetic Peripheral Nerve Stimulation Promotes the Rat Hindlimb Motion Modulation in Stepping: An Experimental Analysis.

Peripheral nerve stimulation is an effective neuromodulation method in patients with lower extremity movement disorders caused by stroke, spinal cord injury, or other diseases. However, most current studies on rehabilitation using sciatic nerve stimulation focus solely on ankle motor regulation through stimulation of common peroneal and tibial nerves. Using the electrical nerve stimulation method, we here achieved muscle control via different sciatic nerve branches to facilitate the regulation of lower limb movements during stepping and standing. A map of relationships between muscles and nerve segments was established to artificially activate specific nerve fibers with the biomimetic stimulation waveform. Then, characteristic curves depicting the relationship between neural electrical stimulation intensity and joint control were established. Finally, by testing the selected stimulation parameters in anesthetized rats, we confirmed that single-cathode extraneural electrical stimulation could activate combined movements to promote lower limb movements. Thus, this method is effective and reliable for use in treatment for improving and rehabilitating lower limb motor dysfunction.

Innervation patterns of hamstring muscles, including morphological descriptions and clinical implication.

The hamstrings muscles are innervated by sciatic nerve branches. However, previous studies assessing which and how many branches innervate each muscle have yielded discrepant results. This study investigated the innervation patterns of hamstrings. Thirty-five cadaver limbs were investigated. The average age of subjects was 78.6 ± 17.2 years, with 48.6% male and 51.4% female, while 57.1% were right limbs and 42.9% left. The sciatic nerve, hamstrings and associated structures were dissected. The number of nerve branches for each muscle and the level where they penetrated the muscle were recorded. The sciatic nerve was connected by a fibrous band to the long head of the biceps femoris. This muscle was innervated by either one or two branches, which penetrated the muscle into its superior or middle third. The short head of the biceps femoris was innervated by a single nerve that usually penetrated its middle third, but sometimes inferiorly or, less commonly, superiorly. The semitendinosus was always innervated by two branches, the superior branch penetrating its upper third, the inferior mostly the middle third. The semimembranosus usually was innervated by a single nerve branch that penetrated the muscle at its middle or lower third. Four specimens revealed common nerves that innervated than one muscle. We have characterized hamstring innervation patterns, knowledge that is relevant to neurolysis, surgery of the thigh, and other procedures. Moreover, a mechanical connection between the sciatic nerve and biceps femoris long head was identified that could explain certain neuralgias.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Neuromuscular choristoma and circumferential nerve territory desmoid-type fibromatosis: imaging findings supporting a nerve-driven mechanism.

Neuromuscular choristoma (NMC) is a rare developmental malformation of peripheral nerve that is frequently associated with the development of a desmoid-type fibromatosis (DTF). Both NMC and NMC-DTF typically contain pathogenic CTNNB1 mutations and NMC-DTF develop only within the NMC-affected nerve territory. The authors aimed to determine if there is a nerve-driven mechanism involved in the formation of NMC-DTF from the underlying NMC-affected nerve. Retrospective review was performed for patients evaluated in the authors' institution with a diagnosis of NMC-DTF in the sciatic nerve (or lumbosacral plexus). MRI and FDG PET/CT studies were reviewed to determine the specific relationship and configuration of NMC and DTF lesions along the sciatic nerve. Ten patients were identified with sciatic nerve NMC and NMC-DTF involving the lumbosacral plexus, sciatic nerve, or sciatic nerve branches. All primary NMC-DTF lesions were located in the sciatic nerve territory. Eight cases of NMC-DTF demonstrated circumferential encasement of the sciatic nerve, and one abutted the sciatic nerve. One patient had a primary DTF remote from the sciatic nerve, but subsequently developed multifocal DTF within the NMC nerve territory, including 2 satellite DTFs that circumferentially encased the parent nerve. Five patients had a total of 8 satellite DTFs, 4 of which abutted the parent nerve and 3 that circumferentially involved the parent nerve. Based on clinical and radiological data, a novel mechanism of NMC-DTF development from soft tissues innervated by NMC-affected nerve segments is proposed, reflecting their shared molecular genetic alteration. The authors believe the DTF develops outward from the NMC in a radial fashion or it arises in the NMC and wraps around it as it grows. In either scenario, NMC-DTF develops directly from the nerve, likely arising from (myo)fibroblasts within the stromal microenvironment of the NMC and grows outward into the surrounding soft tissues. Clinical implications for patient diagnosis and treatment are presented based on the proposed pathogenetic mechanism.

Adductor canal block techniques do not lead to involvement of sciatic nerve branches: a radiological cadaveric study

IntroductionLow and high volume mid-thigh (ie, distal femoral triangle) and distal adductor canal block approaches are frequently applied for knee surgical procedures. Although these techniques aim to contain the injectate...

STUDY OF A VARIATION OF LUMBOSACRAL PLEXUS: SCIATIC NERVE AND ITS CLINICAL SIGNIFICANCE

Background: The pelvis is a home to pelvic parts of the sympathetic and parasympathetic nervous systems, the sacral and coccygeal plexuses, and the lumbosacral trunk. The lower spine’s sciatic nerve is made up of a combination of motor and sensory fibers from spinal nerves fourth lumbar to third sacral segment (ventral rami). The objective of study was to determine morphological variations in origin and formation of branching pattern of sciatic nerve. Methods: A descriptive cross-sectional study was conducted on twenty-four (forty-eight lower limbs) cadavers available in the Department of Anatomy at School of Basic Sciences, Chitwan Medical College. All damaged cadavers were excluded. The cadavers for undergraduate first year medical students dissected as per Cunningham’s Manual. The branching pattern of the sciatic nerve was noted. All Variation of each sacral plexus was photographed. Statistical analysis was done using Microsoft Excel and SPSS version 20. Both gluteal regions were studied for the locations and variation of the sciatic nerve. Results: Forty-eight lower limbs were examined. Among them forty-two lower limbs (87.5 percent) showed a normal anatomy of the sciatic nerve. Six lower limbs (12.5 percent) showed variations in the sciatic nerve. Conclusions: The study concluded that there are variations in origin and formation of branches of sciatic nerve. Variations of sciatic nerve observed could be beneficial for various surgical interventions like nerve release and pain management in compressed nerve.

Triboelectric neurostimulator for physiological modulation of leg muscle

Neurostimulation using triboelectric nanogenerators (TENGs) has been actively researched. However, only limited neural responses have been demonstrated since the previous TENGs could not change stimululs parameters owing to limited operation design and conditions. To overcome these challenges, we report a rotation-based triboelectric neurostimulator (RoTENS) that allows the continuous modulation of stimulus parameters depending on rotation while generating a constant charge output. The RoTENS adjusts the stimulus parameters by controlling the rotational speed and non-contact method. The electrode materials and patterns were optimized, and the characterization of RoTENS was investigated. Furthermore, the neurophysiological validation of hindlimb modulation in rats was demonstrated. By directly stimulating the sciatic nerve branches using RoTENS, dorsiflexion (max. 13.12°) and plantar flexion (maximum 29.34°), which are major movements of the hindlimb for gait, were induced. Varying the frequency (10–50 Hz) allows the muscle to smoothly shift its physiological state from twitching to fused tetanus. The natural relaxation of the muscle is induced by changing the current amplitude via the height of the rotator (0–6 mm). These results indicate that RoTENS is sufficient to induce the desired physiological response while creating wide-ranging frequencies and amplitudes. We expect that RoTENS will open up new opportunities and possibilities for the use of TENG as neurostimulators.

Complex Variations of the Sciatic Nerve Branch and Morphological Variation of the Piriformis Muscle: a Case Report

Complex Variations of the Sciatic Nerve Branch and Morphological Variation of the Piriformis Muscle: a Case Report

Color Doppler ultrasonography of an agitated solution is predictive of accurate catheter placement for a continuous popliteal sciatic nerve block

BackgroundContinuous peripheral nerve catheters (PNCs) have been shown to provide superior postoperative analgesia, decrease opioid consumption, and improve patient satisfaction compared with single injection techniques. In order to achieve success and reliability, accurate catheter positioning is an essential element of PNC placement. An agitated solution of normal saline, D5W, or a local anesthetic solution can be produced by the introduction of air to the injectate, creating air bubbles that can enhance ultrasonographic visualization and possibly improve block success.MethodsEighty-three patients were enrolled. Ultrasound-guided continuous popliteal sciatic nerve blocks were performed by positioning the tip of a Tuohy needle between the tibial and common peroneal branches of the sciatic nerve and threading a catheter. An agitated local anesthetic solution was injected through the catheter, viewed with color Doppler ultrasound and video recorded. A peripheral block score (lower score = greater blockade, range 0-14) was calculated based upon the motor and sensory testing at 10, 20, and 30 min after block completion. The color Doppler agitation coverage pattern for the branches of the sciatic nerve was graded as follows: complete (> 50%), partial (> 0%, ≤ 50%), or none (0%).ResultsThe degree of nerve blockade at 30 min as judged by median (10th, 90th percentile) peripheral block score was significant for partial or complete color Doppler coverage of the sciatic nerve injectate compared to no coverage [3 (0, 7) vs 8 (4, 14); p < 0.01] and block onset was faster (p = 0.03). The block success was higher in groups with partial or complete coverage of the branches of the sciatic nerve vs no coverage (96% vs 70%; p = 0.02).ConclusionsInjection of an agitated solution through a popliteal sciatic perineural catheter is predictive of accurate catheter placement when partial or complete coverage of the sciatic nerve branches is visualized with color Doppler ultrasound.Trial registrationNCT01591603

Improving Nerve Coaptation Outcomes in Targeted Muscle Reinnervation: A Novel Bioengineered Device

PURPOSE: Despite extensive research efforts, neuroma formation remains a persistent challenge in the treatment of peripheral nerve injuries. Targeted muscle reinnervation (TMR) has emerged as a promising approach for prevention and treatment of painful neuromas. However, the significant size-mismatch inherent to TMR contributes to substantial axonal escape from the coaptation site and consequently patients rarely achieve full resolution of symptoms. To address this limitation, we developed a funnel shaped conduit to mechanically guide the regenerating axons across the repair site and thereby prevent axonal escape. The conduit is modified from a biodegradable nerve wrap that has demonstrated excellent biocompatibility and anti-inflammatory properties in prior studies by our group. Given the limited capacity of the distal nerve stump to accept the axons regenerating from the larger proximal nerve, we incorporated chondroitin sulfate proteoglycans (CSPGs) within the lumen of the conduits to inhibit the majority of the regenerating axons. We applied the funnel conduit with and without CSPGs in a TMR model to assess the impact on functional recovery and neuroma formation at the repair site. METHODS: A conduit device composed of nonwoven poly-ε-caprolactone (PCL) was developed by electrospinning. The conduit walls prevent intraneural macrophage infiltration and inflammation, which limits scarring and fibrosis at the coaptation site. Within the conduit, CSPGs incorporated into a nanofiber hydrogel form an interpenetrating network. Using a TMR rodent hindlimb model, we tested the effects of this device on neuroma formation, axonal growth, muscle reinnervation, pain behaviors, and functional recovery. RESULTS: Qualitative assessment of the coaptation site showed that the significant size mismatch between the sciatic nerve and tibial branch resulted in neuroma formation in the TMR and neuroma groups, while the use of the conduit resulted in tapered reinnervation of the sciatic nerve, demonstrating the effectiveness of this device in mechanically guiding axonal growth. Neuroma and TMR groups demonstrated more co-labelling of Substance P and SCG10 (regeneration marker) than conduit groups. No significant differences were observed between the Positive Control and CSPG-Conduit groups in gastrocnemius muscle mass, myofibril cross-sectional area, and neuromuscular junction reinnervation. However, the Positive Control group exhibited significantly greater gastrocnemius mass than the TMR and the Negative Control groups, suggesting better axonal guidance and muscle reinnervation was enabled by the conduit. By Week 5, mechanical stimulation of the coaptation site elicited significantly less pain behavior response scores in the CSPG-Conduit group compared with the Neuroma group. Autotomy scores of CSPG-Conduit scores were similar to Positive Control scores, suggesting successful prevention of neuroma formation. CONCLUSIONS: We introduce a novel engineered device in which mechanical guidance of axons is combined with inhibition of axonal regeneration to prevent neuroma formation. This conduit presents a biologically compatible, noninvasive means by which we could optimize postoperative care of peripheral nerve injury. Built from materials and components currently used in FDA-approved devices, the device is poised for clinical translation. This therapeutic approach has high potential for success as a reliable technique to prevent neuromas and facilitate prosthetic use.

Translating morphology from bench side to bed side via neurophysiology: 8-min protocol for peripheral neuropathy research

BackgroundPeripheral neuropathy treatment is not always satisfactory. To fill this gap, inferences from bench side are warranted, where morphological and pathogenetic determinations can be performed. Nerve conduction studies (NCS) are ideal to translate results from preclinical to clinical setting. New methodsWe propose a comprehensive 8-minute protocol for sensory-motor neurophysiological assessment, similar to routine clinical practice: sensory proximal and distal caudal nerves, motor caudal nerve, and sensory digital nerve recordings were used and tested in 2 different experimental settings. In Experiment 1 we compared control (CTRL) animals to a severe sensory-motor polyneuropathy (animals treated with vincristine [VCR]), and in Experiment 2 CTRL animals were compared to a mild sensory polyneuropathy (animals treated with oxaliplatin [OHP]). NCS were performed after 1-month of chemotherapy and matched with confirmatory neuropathological analyses. ResultsVCR treated animals showed, at NCS, a relevant sensory-motor polyneuropathy ensued at the end of treatment; whereas, OHP animals showed a mild distal sensory neuropathy. These patterns were confirmed by neuropathological analysis. Comparison with existing methodsIn literature, the majority of proposed neurophysiological protocols relies mainly on a single nerve testing, rather than a combination of them, and only a few studies tested both caudal and sciatic nerve branches, nevertheless not aiming at fully reproduce clinical protocols (e.g., seeking for length-dependency); to provide evidence of appropriateness of our protocol we applied a gold standard: neuropathology. ConclusionThe simple and rapid protocol here presented can be suggested as a good translation outcome measure in preclinical setting.

Augmentation of neural activity in peripheral nerve of sheep using 6 kHz subthreshold currents

Objective: To determine how increased excitability from subthreshold currents would alter neural activity as it propagates through the subthreshold currents. Approach: Experiments were performed on two Romney cross-breed sheep in vivo, by applying subthreshold currents either at the stimulus site or between the stimulus and recording sites. Neural recordings were obtained from nerve cuff implanted on the peroneal or sciatic nerve branches, while stimulus was applied to either the peroneal nerve or pins placed through the lower hindshank. Main results: Showed that subthreshold currents applied to the same site as stimulus increased excitation of underlying nerve fibres (p < 0.005). With stimulus and subthreshold currents applied to different sites on the peroneal nerve, the primary compound action potential (CAP) in the sciatic displayed a temporal shift of −2.5 to −3 µs which agreed with changes observed in the CAP waveform (p > 0.05). Significance: These findings contribute to the understanding of mechanisms in myelinated fibres of subthreshold current neuromodulation therapies.

Ultrasound Image Characteristic Analysis of Sciatic Nerve and Main Branches in Third Trimester

The pathogenesis and clinical characteristics of sciatica caused by pregnancy were summarized to reduce the incidence of misdiagnoses and missed diagnoses. The sciatic nerve, tibial nerve, common peroneal nerve, sural nerve, superficial peroneal nerve, saphenous nerve, and lateral femoral cutaneous nerve were examined using ultrasonography for 7 imaging features, including the shape and internal structure of the peripheral nerves of the lower extremities. Randomly selected healthy pregnant women and pregnant women without peripheral nerve damage in the third trimester were examined using a Philips iU22 color Doppler ultrasound scanner with a L12-5 high-frequency probe. The probe was moved anatomically along the peripheral nerves of the lower extremities, including the sciatic nerve, tibial nerve, superficial peroneal nerve, saphenous nerve, and lateral femoral cutaneous nerve. The nerve morphology, structural characteristics, and accompanying blood vessels, tendons, muscles, bones, and other tissues and structures were examined. To determine the site at which to measure the cross-sectional area of the target nerve, we selected places with obvious body surface signs (e.g., popliteal fossa, medial malleolus), less nerve position variation (e.g., neurology start, nerve bifurcation), ultrasound-visible features (e.g., popliteal arteriovenous, fibula head). Ultrasound examination showed that the cross-sections of the peripheral nerves of the lower limbs were triangular, circular, quasicircular, quasitriangular, oval, broad bean-shaped, and drop-shaped. When viewing the same measurement site, the nerve shape was similar and the shape variation was small. However, at different measurement sites, large differences were seen in the shape of the nerves. Hyperechoic shadows are present around the nerves, which make the nerves and adjacent tissues clearly visible. Inside the nerves, at the proximal end of the limbs and in the nerves with larger cross-sections, echo images of varying heights were seen. The arrangement was uniform and regular, and the high echo images were arranged in dots or lines, interlayered with the low echo images to form a honeycomb-like structure. The high and low echo images were arranged uniformly and densely in the distal limbs or inside the small nerves with a small cross section. Arranged in a dot pattern, the structure of nerve walking and accompanying tissues is consistent with the anatomy and is characteristic. We found no significant differences in the peripheral nerve cross-sectional area between the left and right legs but did find a positive correlation with body mass index and age.

Putative Clinical Implications of Unilateral Ossified Sacrospinous Ligament

Abstract Introduction Sacrospinous ligament (SSL) is a thin structure that extends from the ischial spine to the lateral margins of sacrum and coccyx, anterior to the Sacrotuberous ligament (STL). The internal pudendal and inferior gluteal vessels, pudendal nerve, sciatic nerve, and other branches of sacral nerve plexus pass through the greater sciatic foramen (GSF) in close proximity to the ischial spine and SSL. Objective This study aimed to report a case encountered during the routine osteology tutorial, where one of the pelvises presented with ossified SSL on the right side along with ossification of lumbosacral and the sacroiliac joints. Case Report The SSL of the right side of the pelvis was completely ossified, extending between the ischial spine and fifth piece of sacrum. The ossification had a broad-based origin from the sacrum and tapered as in proceeded to the ischial spine. It was attached to the ischial spine with a slight enlargement. Moreover, the lumbosacral and the sacroiliac joints also appeared to be ossified. Conclusion Ossification of the SSL can restrict the lesser sciatic foramen and the greater sciatic foramen, thus causing compression of neurovascular structures traversing these areas. This can be the causative factor in pudendal nerve/sciatic nerve entrapment and can be a cause for undiagnosed chronic perineal pain. Proper anatomical knowledge and radiologic studies can be utilized for accurate diagnosis and treatment of neurovascular compression syndromes and also during reconstructive procedures of the pelvic floor and treatment of uterovaginal prolapse.

Optogenetic activation of muscle contraction in vivo

ABSTRACT Purpose: Optogenetics is an emerging alternative to traditional electrical stimulation to initiate action potentials in activatable cells both ex vivo and in vivo. Optogenetics has been commonly used in mammalian neurons and more recently, it has been adapted for activation of cardiomyocytes and skeletal muscle. Therefore, the aim of this study was to evaluate the stimulation feasibility and sustain isometric muscle contraction and limit decay for an extended period of time (1s), using non-invasive transdermal light activation of skeletal muscle (triceps surae) in vivo. Materials and Methods We used inducible Cre recombination to target expression of Channelrhodopsin-2 (ChR2(H134R)-EYFP) in skeletal muscle (Acta1-Cre) in mice. Fluorescent imaging confirmed that ChR2 expression is localized in skeletal muscle and does not have specific expression in sciatic nerve branch, therefore, allowing for non-nerve mediated optical stimulation of skeletal muscle. We induced muscle contraction using transdermal exposure to blue light and selected 10 Hz stimulation after controlled optimization experiments to sustain prolonged muscle contraction. Results Increasing the stimulation frequency from 10 Hz to 40 Hz increased the muscle contraction decay during prolonged 1s stimulation, highlighting frequency dependency and importance of membrane repolarization for effective light activation. Finally, we showed that optimized pulsed optogenetic stimulation of 10 Hz resulted in comparable ankle torque and contractile functionality to that of electrical stimulation. Conclusions Our results demonstrate the feasibility and repeatability of non-invasive optogenetic stimulation of muscle in vivo and highlight optogenetic stimulation as a powerful tool for non-invasive in vivo direct activation of skeletal muscle.

Sodium channel Nav1.6 in sensory neurons contributes to vincristine-induced allodynia.

Vincristine, a widely used chemotherapeutic agent, produces painful peripheral neuropathy. The underlying mechanisms are not well understood. In this study, we investigated whether voltage-gated sodium channels are involved in the development of vincristine-induced neuropathy. We established a mouse model in which repeated systemic vincristine treatment results in the development of significant mechanical allodynia. Histological examinations did not reveal major structural changes at proximal sciatic nerve branches or distal toe nerve fascicles at the vincristine dose used in this study. Immunohistochemical studies and in vivo two-photon imaging confirmed that there is no significant change in density or morphology of intra-epidermal nerve terminals throughout the course of vincristine treatment. These observations suggest that nerve degeneration is not a prerequisite of vincristine-induced mechanical allodynia in this model. We also provided the first detailed characterization of tetrodotoxin-sensitive (TTX-S) and resistant (TTX-R) sodium currents in dorsal root ganglion neurons following vincristine treatment. Accompanying the behavioural hyperalgesia phenotype, voltage-clamp recordings of small and medium dorsal root ganglion neurons from vincristine-treated animals revealed a significant upregulation of TTX-S Na+ current in medium but not small neurons. The increase in TTX-S Na+ current density is likely mediated by Nav1.6, because in the absence of Nav1.6 channels, vincristine failed to alter TTX-S Na+ current density in medium dorsal root ganglion neurons and, importantly, mechanical allodynia was significantly attenuated in conditional Nav1.6 knockout mice. Our data show that TTX-S sodium channel Nav1.6 is involved in the functional changes of dorsal root ganglion neurons following vincristine treatment and it contributes to the maintenance of vincristine-induced mechanical allodynia.

879 Novel injectable coolant for reducing cutaneous nerve fiber density

Postherpetic neuralgia (PHN) is a dermatologic disorder with no established cure. The distinct dermatomal distribution of PHN makes the peripheral nerve supplying the dermatome and its distal cutaneous branches the ideal therapeutic target; however, the short acting nature of current medications limits the use of this localized approach. Herein we demonstrate the effects of a drug-free, injectable coolant with long-lasting pain suppression capabilities that could potentially be used for treatment of PHN. We have previously reported reduced cutaneous nerve fiber density following topical cooling with cryolipolysis treatment. From here we went on to develop an injectable coolant to target nerves at any anatomic location accessible by a needle. We showed that injection of coolant around the rat sciatic nerve leads to local disruption of myelin. This in turn leads to decrease in nocifensive function for up to 60 days. In this study, using the rat sciatic nerve, we examined the mechanism of reduced nociceptive response after coolant injection. We investigated the effects of the injectable coolant on sciatic nerve branches distal to the injection site and on cutaneous nerve fibers using Coherent anti-Stokes Raman scattering (CARS) microscopy and immunofluorescence (IF) staining. CARS showed myelin degradation in branches distal to the injection site. Corrected correlation parameter index, an indicator for organization of myelin structure, decreased in fibular branch from 0.86±0.08 at baseline to 0.40±0.22 (P<0.0001) at day 14 post injection. Myelinated dermal nerve fiber density was quantified in skin of the hind paw innervated by the sciatic nerve. IF staining showed decreased density of myelinated dermal nerve fibers from baseline value of 56±3/mm2 to 22±3/mm2 (P<0.0001) at day 14. Thus, coolant injection reduces pain by decreasing cutaneous nerve fiber density. Although more work needs to be done, we hope this could potentially be used to treat PHN associated pain.

Analysis of the analgesic effects of tricyclic antidepressants on neuropathic pain, diabetic neuropathic pain, and fibromyalgia in rat models.

ObjectiveTo investigate the analgesic effect of amitriptyline on neuropathic pain model rats, diabetic neuropathic pain model rats and fibromyalgia model rats.MethodsThe healthy male Sprague wrote – Dawley (SD) rats were taken as the research object, and they were randomly divided into model group (group A), beside the sciatic nerve and injection of 5 mm amitriptyline group (group B), beside the sciatic nerve and injection of 10 mm amitriptyline group (group C), beside the sciatic nerve and injection of 15 mm amitriptyline group (group D), intraperitoneal injection of amitriptyline group (group E). Pain induced by selective injury of sciatic nerve branches in rats, pain induced by chronic compression of sciatic nerve, diabetic neuropathic pain and fibromyalgia were conducted to determine the pain threshold of mechanical stimulation in rats after drug administration.ResultsThe pain threshold of mechanical stimulation in the local amitriptyline group (group B, C, D) was significantly higher than that in the group A and group E at each time point after drug treatment, and the pain threshold of mechanical stimulation gradually increased with the increase of concentration. There was no statistically significant difference in mechanical stimulation pain threshold between group A and group E at each time point after drug treatment.ConclusionPara-sciatic injection of amitriptyline at different concentrations has analgesic effects on neuropathic pain, diabetic neuropathic pain and fibromyalgia in rat models, and amitriptyline directly ACTS on the local sciatic nerve.

Variations in the branching pattern of the tibial nerve in the posterior compartment of the leg

Background: Tibial nerve is the largest branch of sciatic nerve. It innervates muscles of the posterior compartment of the leg. Knowledge of the variations in motor branching pattern may help the surgeons when certain procedures are done for calf reduction and also for spastic equinus foot where selective neurectomy is required. It is also required for anesthetists for inducing neurolytic blocks. The aim of the present study was to study the variations in its branching pattern of the tibial nerve in the posterior compartment of the leg. Materials and Methods: The study was done by dissecting forty formalin-fixed lower limbs from twenty adult human cadavers. The origin of tibial nerve, variations, branching pattern, number of muscular branches and termination of the tibial nerve were studied. The level of origin of these nerves was taken in relation to the apex of head of fibula. Results: 57.5% showed that the origin was <12 cm and 42.5% were between 12 and 24 cm above the level of apex of head of fibula. The flexor hallucis longus received one branch in 70% and two branches in 30% of the specimens. Forty percent of the branches showed two or three divisions. The flexor digitorum longus received one branch in 95% and two branches in 5% of the specimens. Eighty percent of the branches of the muscle showed 2–4 divisions. 82.5% of nerve to soleus muscle had one branch and 17.5% had two branches. In 17.5% of the specimens, nerve to soleus originated from the nerve to the lateral head of gastrocnemius. Thirty percent of the branches showed 2–3 divisions. All specimens had one branch which supplied the tibialis posterior muscle and 47.5% of the branches showed 2–3 divisions. In 77.5% of the specimens, the termination occurred above the malleolar calcaneal axis. Conclusion: The flexor hallucis longus, flexor digitorum longus, and soleus muscle had one or two branches from tibial nerve. Single branch innervates tibialis posterior. Nerves to flexor hallucis longus, tibialis posterior, and the soleus had up to three divisions and nerve to flexor digitorum longus had up to four divisions.