Utilization of the Rat Tibial Nerve Transection Model to Evaluate Cellular and Molecular Mechanisms Underpinning Denervation-Mediated Muscle Injury.

Peripheral nerve injury denervates muscle, resulting in muscle paralysis and atrophy. This is reversible if timely muscle reinnervation occurs. With delayed reinnervation, the muscle's reparative ability declines, and muscle-resident fibro-adipogenic progenitor cells (FAPs) proliferate and differentiate, inducing fibro-fatty muscle degradation and thereby physical disability. The mechanisms by which the peripheral nerve regulates FAPs expansion and differentiation are incompletely understood. Using the rat tibial neve transection model, we demonstrated an increased FAPs content and a changing FAPs phenotype, with an increased capacity for adipocyte and fibroblast differentiation, in gastrocnemius muscle post-denervation. The FAPs response was inhibited by immediate tibial nerve repair with muscle reinnervation via neuromuscular junctions (NMJs) and sensory organs (e.g., muscle spindles) or the sensory protection of muscle (where a pure sensory nerve is sutured to the distal tibial nerve stump) with reinnervation by muscle spindles alone. We found that both procedures reduced denervation-mediated increases in glial-cell-line-derived neurotrophic factor (GDNF) in muscle and that GDNF promoted FAPs adipogenic and fibrogenic differentiation in vitro. These results suggest that the peripheral nerve controls FAPs recruitment and differentiation via the modulation of muscle GDNF expression through NMJs and muscle spindles. GDNF can serve as a therapeutic target in the management of denervation-induced muscle injury.

Chitosan-Based Conduits with Different Inner Diameters at both Ends Combined with Modified Formula Radix Hedysari Promote Nerve Transposition Repair.

BACKGROUND: Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. An innovative approach to repairing severe peripheral nerve damage involves using conduit suturing for nerve transposition repair. Cylindrical nerve guides are typically unsuitable for nerve transposition repair. Moreover, postsurgical adjuvant treatment is essential to promote the development of axonal lateral sprouts, proximal growth, and the restoration of neurostructure and function. The purpose of this research is to assess the impact of chitosan-based conduits with varying inner diameters on nerve transposition repair when combined with modified formula Radix Hedysari (MFRH). METHODS: Using chitosan, we created conduits with varying inner diameters on both ends. These conduits were then utilized to repair the distal common peroneal and tibial nerves in SD rats using the proximal common peroneal nerve. Subsequently, MFRH was employed as a supplementary treatment. The assessment of the repair's effectiveness took place 16 weeks postsurgery, utilizing a range of techniques, including the neurological nerve function index, neuroelectrophysiological measurements, muscle wet weight, and examination of nerve and muscle histology. RESULTS: The outcomes of our study showed that following 16 weeks of postoperative treatment, MFRH had a significant positive impact on the recovery of neuromotor and nerve conduction abilities. Moreover, there was a significant increase in the ratio of wet weight of muscles, cross-sectional area of muscle fibers, quantity and structure of regenerated myelinated nerve fibers, and the count of neurons. CONCLUSIONS: A combination of chitosan-based chitin conduits possessing different inner diameters and MFRH can considerably promote the regeneration and functional recovery of damaged nerves, which in turn enhances nerve transposition repair efficacy.

Reversal of cold intolerance by testosterone in orchiectomized mice after tibial nerve transection.

Cold intolerance is a debilitating effect of nerve injury, has a strong impact on the life of patients and no advisable treatment exists against it. Testosterone influences pain pathways and has analgesic effects. A recent study showed testosterone as being an agonist of TRPM8, the predominant ion channel that contributes to cold hypersensitivity after injury. We investigated the effect of testosterone on cold sensitivity after nerve injury. Specifically, using the double plate test (DPT) (thermo-neutral-plate: 31 ºC and cold-plate: 18 ºC) we determined the thermal preference of mice at different points during the study design consisting of: orchiectomy, tibial nerve transection (TNT) (30 days after orchiectomy), 15-days-repeated subcutaneous injections of testosterone enanthate (250 or 500 µg/kg/day) or vehicle (started 12 h after TNT surgery). Different parameters such as time spent on cold plates, distance traveled, animal speed on the cold- and thermo-neutral-plates were determined in naïve, sham and neuropathic animals. Neither orchiectomy nor sham TNT surgery generate effects on cold intolerance and animal activity while TNT surgery decreased the time spent on the cold-plate and the distance traveled during DPT. Testosterone administration reversed the effect of nerve injury, decreasing the cold hypersensitivity and increasing activity of TNT mice. However, the effect of testosterone on cold avoidance reduced with time and at 14 days after TNT surgery, a higher dose was needed to reverse the effect generated by nerve injury. This indicates that although testosterone administration has a positive effect on cold intolerance, it might not be suitable for prolongated treatment.

Reporte de caso: radiofrecuencia de nervio de Baxter en paciente con fascitis plantar refractaria a manejo convencional / Case report: Baxters nerve radiofrequency in patient with plantar fasciitis nonresponsive to conventional treatment

La fascitis plantar es reconocida como la principal causa de talalgia a nivel mundial, en la gran mayoría de casos se logra controlar con uso de calzado adecuado, ejercicios de estiramiento y cambios en la actividad deportiva, unos pocos casos requieren infiltraciones o intervenciones quirúrgicas, esta última supone un riesgo mayor para el paciente siendo reservada para los casos más severos.Se propone el uso de radiofrecuencia pulsada del nervio de Baxter como una de las opciones de manejo del síntoma doloroso en aquellos pacientes en los que no se obtenga adecuada respuesta al tratamiento convencional. Exponemos el caso de una paciente con fascitis plantar refractaria, no candidata a cirugía, quien fue llevada a radiofrecuencia pulsada con resultados satisfactorios a corto y medio plazo.(AU)

Plantar fasciitis is recognized as the leading cause of talalgia worldwide. In the vast majority of cases it can be controlled with the use of appropriate footwear, stretching exercises and changes in the sport activity, while a few cases require infiltrations or surgical interventions. The latter puts the patient at greater risk, and is reserved for the most severe cases. We propose using pulsed radiofrequency ablation of Baxter's nerve to treat this painful symptom in patients who do not respond adequately to conventional treatment. We present the case of a patient with refractory plantar fasciitis in whom surgery had been ruled out. The patient underwent pulsed radiofrequency treatment with satisfactory results in the short and medium term.(AU)

Short-Duration, Pulsatile, Electrical Stimulation Therapy Accelerates Axon Regeneration and Recovery following Tibial Nerve Injury and Repair in Rats.

BACKGROUND: Repair of nerve injuries can fail to achieve adequate functional recovery. Electrical stimulation applied at the time of nerve repair can accelerate axon regeneration, which may improve the likelihood of recovery. However, widespread use of electrical stimulation may be limited by treatment protocols that increase operative time and complexity. This study evaluated whether a short-duration electrical stimulation protocol (10 minutes) was efficacious to enhance regeneration following nerve repair using rat models. METHODS: Lewis and Thy1-green fluorescent protein rats were randomized to three groups: 0 minutes of electrical stimulation (no electrical stimulation; control), 10 minutes of electrical stimulation, and 60 minutes of electrical stimulation. All groups underwent tibial nerve transection and repair. In the intervention groups, electrical stimulation was delivered after nerve repair. Outcomes were assessed using immunohistochemistry, histology, and serial walking track analysis. RESULTS: Two weeks after nerve repair, Thy1-green fluorescent protein rats demonstrated increased green fluorescent protein-positive axon outgrowth from the repair site with electrical stimulation compared to no electrical stimulation. Serial measurement of walking tracks after nerve repair revealed recovery was achieved more rapidly in both electrical stimulation groups as compared to no electrical stimulation. Histologic analysis of nerve distal to the repair at 8 weeks revealed robust axon regeneration in all groups. CONCLUSIONS: As little as 10 minutes of intraoperative electrical stimulation therapy increased early axon regeneration and facilitated functional recovery following nerve transection with repair. Also, as early axon outgrowth increased following electrical stimulation with nerve repair, these findings suggest electrical stimulation facilitated recovery because of earlier axon growth across the suture-repaired site into the distal nerve to reach end-organ targets. CLINICAL RELEVANCE STATEMENT: Brief (10-minute) electrical stimulation therapy can provide similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair rat model and merit further studies, as they represent a translational advantage.

Síndrome del túnel del tarso: análisis clínico-imagenológico de una serie de casos / Tarsal tunnel syndrome: Clinical-imaging analysis of a case series

Antecedentes: Revisión retrospectiva de pacientes con diagnóstico de síndrome del túnel del tarso (STT) tratados quirúrgicamente. Método: Serie retrospectiva de pacientes con diagnóstico de STT operados entre los años 2005 y 2020 en un mismo centro. Se analizan variables como edad, género, lado, nervio o rama afectada, clasificación, tipo de estudio imagenológico, resultado biopsia, tasa de infección, tasa recurrencia, secuelas, entre otras. Resultados: Se incluyen ocho hombres y dos mujeres con edad promedio de 47 años (rango 34-67) y seguimiento promedio de 62,2 meses (rango 2-149). Todos los casos se relacionan con una compresión intrínseca. La causa más frecuente fue la presencia de quiste (40%), seguida de adherencias perineurales (20%). El nervio tibial posterior fue el más afectado (50%) y 30% la rama plantar medial. La ecografía (70%) y resonancia magnética (50%) fueron los estudios más solicitados. No hubo casos de infección postoperatoria. Hubo tres pacientes que presentaron recurrencia de la lesión requiriendo una nueva cirugía. Conclusiones: El STT es una neuropatía que compromete al nervio tibial posterior o a algunas de sus ramas. En general su causa es la compresión del nervio por distintas estructuras como músculos accesorios, gangliones, entre otras. El diagnóstico es eminentemente clínico apoyándose en estudio por imágenes. El tratamiento quirúrgico presenta mejores resultados cuando la causa es una compresión intrínseca, aunque se describen tasas variables de recurrencia.(AU)

Background: Retrospective review of patients with a diagnosis of Tarsal Tunnel Syndrome (TTS) treated surgically. Methods: Retrospective series of patients with diagnosis of TTS operated between 2005 and 2020 in the same center. Variables such as age, sex, side, affected nerve or branch, classification, type of imaging study, biopsy result, infection rate, recurrence rate, sequelae, among others, were analyzed. Results: We included 8 men and 2 women with an average age of 47 years (range 34-67) and an average follow-up of 62.2 months (range 2-149). All cases were related to intrinsic compression. The most frequent cause was the presence of cyst (40%) followed by perineural adhesions (20%). The Posterior Tibial Nerve was the most affected (50%) and 30% the Medial Plantar Branch. Ultrasound (70%) and MRI (50%) were the most requested studies. There were no cases of postoperative infection. There were 3 patients who presented recurrence of the lesion requiring a new surgery. Conclusions: TTS is a neuropathy involving the posterior tibial nerve or some of its branches. In general, it is caused by compression of the nerve by different structures such as accessory muscles and ganglions, among others. The diagnosis is eminently clinical, supported by imaging studies. Surgical treatment presents better results when the cause is an intrinsic compression, although variable recurrence rates are described.(AU)

Tarsal tunnel syndrome: Clinical-imaging analysis of a case series / Síndrome del túnel del tarso: análisis clínico-imagenológico de una serie de casos

Background: Retrospective review of patients with a diagnosis of Tarsal Tunnel Syndrome (TTS) treated surgically. Methods: Retrospective series of patients with diagnosis of TTS operated between 2005 and 2020 in the same center. Variables such as age, sex, side, affected nerve or branch, classification, type of imaging study, biopsy result, infection rate, recurrence rate, sequelae, among others, were analyzed. Results We included 8 men and 2 women with an average age of 47 years (range 34-67) and an average follow-up of 62.2 months (range 2-149). All cases were related to intrinsic compression. The most frequent cause was the presence of cyst (40%) followed by perineural adhesions (20%). The Posterior Tibial Nerve was the most affected (50%) and 30% the Medial Plantar Branch. Ultrasound (70%) and MRI (50%) were the most requested studies. There were no cases of postoperative infection. There were 3 patients who presented recurrence of the lesion requiring a new surgery. Conclusions: TTS is a neuropathy involving the posterior tibial nerve or some of its branches. In general, it is caused by compression of the nerve by different structures such as accessory muscles and ganglions, among others. The diagnosis is eminently clinical, supported by imaging studies. Surgical treatment presents better results when the cause is an intrinsic compression, although variable recurrence rates are described.(AU)

Antecedentes: Revisión retrospectiva de pacientes con diagnóstico de síndrome del túnel del tarso (STT) tratados quirúrgicamente. Método: Serie retrospectiva de pacientes con diagnóstico de STT operados entre los años 2005 y 2020 en un mismo centro. Se analizan variables como edad, género, lado, nervio o rama afectada, clasificación, tipo de estudio imagenológico, resultado biopsia, tasa de infección, tasa recurrencia, secuelas, entre otras. Resultados: Se incluyen ocho hombres y dos mujeres con edad promedio de 47 años (rango 34-67) y seguimiento promedio de 62,2 meses (rango 2-149). Todos los casos se relacionan con una compresión intrínseca. La causa más frecuente fue la presencia de quiste (40%), seguida de adherencias perineurales (20%). El nervio tibial posterior fue el más afectado (50%) y 30% la rama plantar medial. La ecografía (70%) y resonancia magnética (50%) fueron los estudios más solicitados. No hubo casos de infección postoperatoria. Hubo tres pacientes que presentaron recurrencia de la lesión requiriendo una nueva cirugía. Conclusiones: El STT es una neuropatía que compromete al nervio tibial posterior o a algunas de sus ramas. En general su causa es la compresión del nervio por distintas estructuras como músculos accesorios, gangliones, entre otras. El diagnóstico es eminentemente clínico apoyándose en estudio por imágenes. El tratamiento quirúrgico presenta mejores resultados cuando la causa es una compresión intrínseca, aunque se describen tasas variables de recurrencia.(AU)

The Role of TMEM16A/ERK/NK-1 Signaling in Dorsal Root Ganglia Neurons in the Development of Neuropathic Pain Induced by Spared Nerve Injury (SNI).

Increasing evidence suggests that transmembrane protein 16A (TMEM16A) in nociceptive neurons is an important molecular component contributing to peripheral pain transduction. The present study aimed to evaluate the role and mechanism of TMEM16A in chronic nociceptive responses elicited by spared nerve injury (SNI). In this study, SNI was used to induce neuropathic pain. Drugs were administered intrathecally. The expression and cellular localization of TMEM16A, the ERK pathway, and NK-1 in the dorsal root ganglion (DRG) were detected by western blot and immunofluorescence. Behavioral tests were used to evaluate the role of TMEM16A and p-ERK in SNI-induced persistent pain and hypersensitivity. The role of TMEM16A in the hyperexcitability of primary nociceptor neurons was assessed by electrophysiological recording. The results show that TMEM16A, p-ERK, and NK-1 are predominantly expressed in small neurons associated with nociceptive sensation. TMEM16A is colocalized with p-ERK/NK-1 in DRG. TMEM16A, the MEK/ERK pathway, and NK-1 are activated in DRG after SNI. ERK inhibitor or TMEM16A antagonist prevents SNI-induced allodynia. ERK and NK-1 are downstream of TMEM16A activation. Electrophysiological recording showed that CaCC current increases and intrathecal application of T16Ainh-A01, a selective TMEM16A inhibitor, reverses the hyperexcitability of DRG neurons harvested from rats after SNI. We conclude that TMEM16A activation in DRG leads to a positive interaction of the ERK pathway with activation of NK-1 production and is involved in the development of neuropathic pain after SNI. Also, the blockade of TMEM16A or inhibition of the downstream ERK pathway or NK-1 upregulation may prevent the development of neuropathic pain.

Effect of Nimodipine and Botulinum Toxin A on Peripheral Nerve Regeneration in Rats: A Pilot Study.

BACKGROUND: Peripheral nerve damage is a frequent problem, with an estimated 2.8%-5.0% of trauma admissions involving peripheral nerve injury. End-to-end, tension-free microsurgical repair (neurorrhaphy) is the current gold standard treatment for complete transection (neurotmesis). While neurorrhaphy reapproximates the nerve, it does not address the complex molecular regenerative process. Evidence suggests that botulinum toxin A (BTX) and nimodipine (NDP) may improve functional recovery, but mechanisms of action remain unknown. METHODS: This research investigates BTX and NDP for their novel capacity to improve neural regeneration in the setting of neurorrhaphy using a Lewis rat tibial nerve neurotmesis model. In a triple-masked, placebo-controlled, randomized study design, we compared functional (rotarod, horizontal ladder walk), electrophysiological (conduction velocity, duration), and stereological (axon count, density) outcomes of rats treated with: NDP+saline injection, BTX+NDP, Saline+placebo, and BTX+placebo. Additional controls included sham surgery +/- BTX. RESULTS: NDP+saline outperformed other treatment groups in the ladder walk. This group had the fewest deep slips (15.07% versus 30.77% in BTX+NDP, P = 0.122), and the most correct steps (70.53% versus 55.58% in BTX+NDP, P = 0.149) in functional testing. NDP+saline also had the fastest nerve conduction velocity (0.811m/s versus 0.598m/s in BTX+NDP, P = 0.126) among treatment groups. BTX+NDP had the highest axon count (10,012.36 versus 7,738.18 in NDP+Saline, P = 0.009). CONCLUSION: This study is the first to test NDP with BTX in a multimodal assessment of nerve recovery following neurotmesis and neurorrhaphy. NDP outperformed BTX+NDP functionally. Future work will focus on nimodipine in an effort to improve nerve recovery in trauma patients.

Unrecognized tibial nerve injury in total-ankle arthroplasty: Two case reports.

RATIONALE: Tibial nerve injury is a sustainable but rare complication during total-ankle arthroplasty (TAA). We outlined 2 previously unreported cases of tibial nerve injury in TAA, including the prognoses and possible causes. PATIENT CONCERNS: First, a 63-year-old woman complained of a 5-month history of persistent tingling sensation and numbness on the medial and plantar aspects of her foot after TAA. Second, a 50-year-old woman complained of a 6-month history of tingling sensation and numbness on the plantar surface of her forefoot after TAA. DIAGNOSIS: Explorations were performed on suspicion of tarsal tunnel syndrome; however, both patients exhibited complete laceration of tibial nerve with neuroma formation. INTERVENTIONS: In both patients, we excised the neuroma and performed end-to-end nerve repair. OUTCOMES: The sensory disturbance of the sole considerably improved at long-term follow-up over 8 years after the neurorrhaphy procedures. LESSONS: Tibial nerve injury is rare following TAA, and is sometimes unrecognized or misdiagnosed. If tibial nerve injury is suspected, prompt surgical exploration should be performed; great precaution must also be taken to prevent injury of the tibial nerve during TAA.

Initial Evaluation and Classification of Knee Dislocations.

The traumatic knee dislocation (KD) is a complex condition resulting in injury to >1 ligament or ligament complexes about the knee, termed multiligament knee injuries. Typically, KDs result in injury to both cruciate ligaments with variable injury to collateral ligament complexes. Very rarely, KD may occur with single cruciate injuries combined with collateral involvement but it is important to understand that not all multiligament knee injuries are KDs. Patients can present in a wide spectrum of severity; from frank dislocation of the tibiofemoral joint to a spontaneously reduced KD, either with or without neurovascular injury. The initial evaluation of these injuries should include a thorough patient history and physical examination, with particularly close attention to vascular status which has the most immediate treatment implications. Multiple classification systems have been developed for KDs, with the anatomic classification having the most practical application.

[Selective ultrasound-guided hydrodissection of gastrocnemius nerve branch after post-surgical entrapment: Apropos of a case]. / Hidrodisección ecoguiada selectiva de rama nerviosa gemelar tras atrapamiento posquirúrgico: a propósito de un caso.

Chronic or recalcitrant plantar fasciitis is a cause of persistent plantar pain. These cases are usually resistant to conventional treatments consisting of exercises, orthoses, shock waves and infiltrations and require a surgical approach. Proximal medial gastrocnemius release is a surgical option that provides satisfactory results, but is not free of complications, which include injuries and nerve entrapment. We report the first published case of symptomatic medial gastrocnemius branch entrapment in the post-surgical scar of a tenotomy for the treatment of recalcitrant plantar fasciitis. We propose ultrasound-guided hydrodissection with local anesthetic as a treatment with promising results.

Musculoskeletal ultrasonography combined with electromyography in the diagnosis of massage-inducted lateral plantar nerve injury: A case report.

INTRODUCTION: It is well known that foot massage is a very prevalent stress relief method in China. Literatures have reported various massage-inducted peripheral nerve injuries. However, massage-inducted lateral plantar nerve (LPN) injury is very rare. Here, we represent an unusual case of massage-inducted LPN damage, and we also report the diagnostic method of this patient using musculoskeletal ultrasonography combined with electromyography (EMG). PATIENT CONCERNS: A 21-year-old woman presented symptoms of redness, swelling, pain and numbness in the medial right ankle joint for 2 days. DIAGNOSIS: The results of musculoskeletal ultrasonography and EMG provide great help for doctors to make accurate diagnosis. The patient was eventually diagnosed with LPN injury. INTERVENTIONS: No further foot massage was allowed. Vitamin B12 was taken orally for 2 months. Conservative therapy, including electrical stimulation therapy and infrared therapy, was conducted. Besides, active rehabilitation training was also performed. OUTCOMES: The discomfort symptoms were relieved significantly after 2 months conservative treatment. Clinical symptoms and EMG examination illustrated satisfactory result during follow up time. CONCLUSION: The report showed that the masseur should be very careful when doing foot massage to prevent nerve damage. Besides, musculoskeletal ultrasonography combined with EMG can provide important evidence for accurate and effective diagnosis of LPN injury.

[Closed medial talus dislocation with damage to the tibial nerve]. / Geschlossene mediale Talusluxation mit N.-tibialis-Schädigung.

This article reports a case of medial dislocation of the talus as a rare injury caused by a fall from a low height.Treatment recommendations given in the literature for this rare injury are heterogeneous but closed reduction is predominant. Little is known about possible obstacles in closed reduction. The known complications include posttraumatic arthritis and necrosis of the talus.A posttraumatic lesion of the tibial nerve has not been reported, which is why a treatment recommendation is illustrated and discussed based on this case report.

Anatomical Considerations of Infrageniculate Popliteal Artery Puncture: Alternative Pathway for Retrograde Access After Failed Re-entry.

BACKGROUND: A distal approach in endovascular procedures for revascularization of lowers limbs can be considered in case of no re-entry in subintimal recanalization. The aim of this study is to evaluate the feasibility of a medial approach to the infrageniculate popliteal artery (IPA) using existing computed tomography (CT) scan simulation and punctures performed on cadavers. METHODS AND RESULTS: CT angiographies of lower extremities were used to simulate IPA puncture and puncture trajectory. Tissues damaged during the trajectory between the puncture site and the access-related injuries were analyzed. Anatomical punctures on cadaverous model were also performed. Corpses were placed in supine position, the hip in slight flexion (40°) and abduction (external rotation of 60°). A 16 G needle was used for the IPA puncture. Twelve CT angiography simulations were made. Of these 12 simulations, 9 revealed an isolated lesion of the popliteal vein and 2 isolated lesions of the tibial nerve. A lesion of the tibial nerve and the popliteal vein on the same simulation was once observed. Damage to the medial gastrocnemius muscle could not be avoided in each case. Ten punctures were performed on cadavers with technical success. There were 6 popliteal vein lesions, 3 tibial nerve lesions, and 1 case without lesion. In all cases, damage to the medial gastrocnemius muscle was seen. CONCLUSIONS: This medial approach was feasible and is accompanied by trauma of elements of the popliteal pedicle. Preoperative CT angiography could anticipate best site of puncture and potential access-related injury.

Schwannoma of the Posterior Tibial Nerve.

A 61-year-old woman was referred to physical therapy by a podiatrist who suspected a posterior tibialis degenerative tear. To further examine the irritable posterior tibial nerve, a musculoskeletal ultrasound examination was performed, showing a vascularized focal lesion suggestive of a nerve tumor. The patient was referred back to the referring podiatrist, who ordered magnetic resonance imaging, which confirmed the schwannoma of the posterior tibialis nerve. J Orthop Sports Phys Ther 2020;50(2):111. doi:10.2519/jospt.2020.9103.

Development and persistence of neuropathic pain through microglial activation and KCC2 decreasing after mouse tibial nerve injury.

Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter in the mature brain, but is excitatory during development and after motor nerve injury. This difference in GABAergic action depends on the intracellular chloride ion concentration ([Cl-]i), primarily regulated by potassium chloride co-transporter 2 (KCC2). To reveal precise processes of the neuropathic pain through changes in GABAergic action, we prepared tibial nerve ligation and severance models using male mice, and examined temporal relationships amongst changes in (1) the mechanical withdrawal threshold in the sural nerve area, (2) localization of the molecules involved in GABAergic transmission and its upstream signaling in the dorsal horn, and (3) histology of the tibial nerve. In the ligation model, tibial nerve degeneration disappeared by day 56, but mechanical allodynia, reduced KCC2 localization, and increased microglia density remained until day 90. Microglia density was higher in the tibial zone than the sural zone before day 21, but this result was inverted after day 28. In contrast, in the severance model, all above changes were detected until day 28, but were simultaneously and significantly recovered by day 90. These results suggested that in male mice, allodynia may be caused by reduced GABAergic synaptic inhibition, resulting from elevated [Cl-]i after the reduction of KCC2 by activated microglia. Furthermore, our results suggested that factors from degenerating nerve terminals may diffuse into the sural zone, whereby they induced the development of allodynia in the sural nerve area, while other factors in the sural zone may mediate persistent allodynia through the same pathway.

Nerve Repair and Orthodromic and Antidromic Nerve Grafts: An Experimental Comparative Study in Rabbit.

PURPOSE: Although many surgeons have anecdotally described reversing the polarity of the autograft with the intent of improving regeneration, the optimal orientation of the autogenous nerve graft remains controversial. The aim of this study was to compare (1) the outcomes of orthodromic and antidromic nerve grafts to clarify the effect of nerve graft polarity and (2) the outcome of either form of nerve grafts with that of nerve repair. METHODS: In 14 of the 26 rabbits used in this study, a 1 cm defect was made in the tibial nerve. An orthodromic nerve graft on one side and an antidromic nerve graft on the other were performed using a 1.2 cm long segment of the peroneal nerve. In the remaining 12 rabbits, the tibial nerve was transected completely and then repaired microscopically on one side but left untreated on the other. Electrophysiologic studies were performed in all animals at 8 weeks after surgery, and the sciatic nerves were harvested. RESULTS: Compound motor action potential was visible in all rabbits treated by nerve repair but in only half of the rabbits treated by nerve graft. There was no significant difference in the compound motor action potential, nerve conduction velocity, or total number of axons between the orthodromic and antidromic nerve graft groups. However, in both groups, the outcome was significantly poorer than that of the nerve repair group. CONCLUSION: There was no significant difference by electromyographic or histologic evaluation between orthodromic and antidromic nerve grafts. Direct nerve repair with moderate tension may be a more effective treatment than nerve grafting.

The injection site in the tarsal tunnel to minimize neurovascular injury for heel pain: an anatomical study.

INTRODUCTION: The aim of this study was to investigate the location and distribution patterns of neurovascular structures and determine the effective injection point in the tarsal tunnel for heel pain. METHODS: Fifteen adult non-embalmed cadavers with a mean age of 71.5 years were studied. The most inferior point of the medial malleolus of the tibia (MM) and the tuberosity of the calcaneus (TC) were identified before dissection. A line connecting the MM and TC was used as a reference line. The reference point was expressed in absolute distance along the reference line using the MM as the starting point. For measurements using MRI, the depth from the skin was measured to inferior at an interval of 1 cm from the MM. RESULTS: The posterior tibial artery, lateral plantar nerve, and medial plantar nerve were located from 29.0 to 37.3% of the reference line from the MM. The distribution frequencies of the medial calcaneal nerve on the reference line from the MM were 0%, 8.60%, 37.15%, 37.15%, and 17.10%, respectively. The mean depth of the neurovascular structures was 0.3 cm. DISCUSSION: This study recommended an effective injection site from 45.0 to 80.0% of the reference line.

Side-to-side supercharging nerve allograft enhances neurotrophic potential.

INTRODUCTION: Critical limitations of processed acellular nerve allograft (PNA) are linked to Schwann cell function. Side-to-side bridge grafting may enhance PNA neurotrophic potential. METHODS: Sprague-Dawley rats underwent tibial nerve transection and immediate repair with 20-mm PNA (n = 33) or isograft (ISO; n = 9) or 40-mm PNA (n = 33) or ISO (n = 9). Processed acellular nerve allograft groups received zero, one, or three side-to-side bridge grafts between the peroneal nerve and graft. Muscle weight, force generation, and nerve histomorphology were tested 20 weeks after repair. Selected animals underwent neuron back labeling with fluorescent dyes. RESULTS: Inner axon diameters, g-ratios, and axon counts were smaller in the distal vs proximal aspect of each graft (P < .05). Schwann cell counts were greater, with a lower proportion of senescent cells for groups with bridges (P < .05). Retrograde labeling demonstrated that 6.6% to 17.7% of reinnervating neurons were from the peroneal pool. DISCUSSION: Bridge grafting positively influenced muscle recovery and Schwann cell counts and senescence after long PNA nerve reconstruction.