Peripheral BDNF Regulates Somatosensory-Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain / 神经科学通报·英文版

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.

Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats / 神经科学通报·英文版

After brachial plexus avulsion (BPA), microglia induce inflammation, initiating and maintaining neuropathic pain. EZH2 (enhancer of zeste homolog 2) has been implicated in inflammation and neuropathic pain, but the mechanisms by which it regulates neuropathic pain remain unclear. Here, we found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) secretion in vivo. In rats with BPA-induced neuropathic pain, mechanical and cold hypersensitivities were induced by EZH2 upregulation and inhibited by EZH2 downregulation in the anterior cingulate cortex. Microglial autophagy was also significantly inhibited, with EZH2 inhibition activating autophagy and reducing neuroinflammation in vivo. However, this effect was impaired by inhibiting autophagy with 3-methyladenine, suggesting that the MTOR signaling pathway is a functional target of EZH2. These data suggest that EZH2 regulates neuroinflammation and neuropathic pain via a novel MTOR-mediated autophagy signaling pathway, providing a promising approach for managing neuropathic pain.

G7nerve double-neurotization in the treatment of total brachial plexus avulsion: An experimental study / 中华显微外科杂志

Objective To test the feasibility of rescuing 2 impaired nerves by C7 nerve transfer (C7 nerve double-neurotization). Methods Using adult male Sprague-Dawley rats(200 - 250 g),a C7 nerve double-neurotization model was established. At postoperative 2, 4, 6, 8, 12th weeks the recovery underwent muscle-nerve morpholosical, histological examinations and was compared with C7 single neurotization, Results Most of the parameters in double neurotization group approximated to those in the single neurotization groups and normal control group at the end of observation period, thus indicating C7 nerve contains enough nerve fibers to provide sufficient regeneration for 2 recipient nerves. Conclusion Compared to single neurotization, C7 nerve double-neurotization has the advantage of restoring 2 nerve function at same time. This implicates its future clinical application in the treatment of severe brachial plexus avulsion injuries.

Clinical results of different ways of neurotization to radial nerve / 中华创伤杂志

Objective To compare the result differences of different dynamic nerves transferring to different segments of the radial nerve. Methods From 1997 to 2000, different ways of intercostal nerves or contralataral C 7 transfering to different segments of the radial nerves were carried out in 36 cases with total avulsed brachial plexus injuries that were followed up for average 42.39 months. Four-fold table was selected to statistically calculate the effective rate of muscle strength recovery. Results The total effective rate was 56% (20/36). The effective rate of the functional rehabilitation of elbow extension was 5/8 in the group with neurotization to radial nerve trunk and 4/4 in the group with neurotization to branches innervating the triceps brachii muscle of radial nerve. The highest effective rate up to 75% (9/12) of the functional rehabilitation of wrist and digit extension belonged to the group with contralateral C 7 transferring to the radial nerve segment in the humeral spiral groove where branches innervating the triceps brachii muscle had already diverged. Conclusions The way of neurotization to radial nerve trunk and to branches innervating the triceps brachii muscle of the radial nerve can win good functional rehabilitation of elbow extension. Contralataral C 7 transfering to the radial nerve segment in the humeral spiral groove ranks the best way for function recovery of the wrist extension. Age below 30 years and operation interval less than 12 months are helpful for functional rehabilitation of the radial nerve.

The Results of DREZ Operation on Deafferentation Pain

OBJECTIVE: The authors present dorsal root entry zone(DREZ) operations on deafferentation pain patients suffered from brachial plexus avulsion(BPA), phantom pain(PP) and postherpetic pain(PHP). METHODS: Eight patients(Six BPA, one PP and one PHP) underwent DREZ operations on the cervical, thoracic and thoracolumbar spinal cords. The patients were 7 men and 1 woman who were in between thirties and sixties. The lesions were made by inserting 2mm bare tip of standard type DREZ electrode connected to Radionics radiofrequency generator into the DREZ 45 degree off the sagittal plane. The tissue was heated to 75degrees C for 15 seconds. RESULTS: All BPA patients had immediate and long-lasting pain relief regardless of the duration and character of the pain but patients with PP and PHP complained rather aggravation of pain after the operation. CONCLUSION: DREZ operation is effective for BPA pain, however, it needs to have attention in performing this surgery for PP or PHP.

Avulsão do plexo braquial em cães -1: aspectos clínicos e neurológicos / Brachial plexus avulsion in dogs -1: clinical and neurological aspects

A avulsão do plexo braquial é afecção de ordem traumática relativamente comum, ocasionando paralisia grave do membro torácico. É freqüentemente confundida com paralisia do nervo radial, havendo controvérsias sobre o tratamento. O objetivo deste trabalho foi: avaliar clinica e neurologicamente cães com avulsão do plexo braquial, demonstrando os aspectos significativos para o diagnóstico desta afecção. Observou-se predominância de cães sem raça definida, fêmea, com menos de três anos de idade, sendo o atropelamento a etiologia principal. As alterações clinicam/neurológicas mais freqüentes foram: paralisia flácida, ausência do reflexo dopanículo, ausência dos reflexos tricipital, bicipital e extensor do carpo radial, atrofia dos músculos tríceps, bíceps, supra-espinhal, infra-espinhal e extensores do carpo, anestesia cutânea abaixo do nível do cotovelo e abrasão/ulceração em face dorsal da mão. A associação destes resultados com os aspectos da histologia e da eletroneuroestimulação (relatados na parte 2 e 3 deste trabalho, respectivamente) sugeriu envolvimento quase que total das raízes do plexo braquial em todos os casos.

Brachial plexus avulsion is a relatively common affection, causing serious paralysis of the thoracic limb. It is often misdiagnosed as radial paralysis and there are controversies about the treatment. The main purposes of this work were: to evaluate clinically and neurologically dogs with brachial plexus avulsion and to demonstrate the relevant aspects in the diagnosis of this affection. Predominantly mixed breed dogs, females under three years of age were observed, and the brachial plexus avulsion was mainly a result of road accidents. The more frequent clinical and neurological signs were: flacid paralysis, loss of the panniculus, triceps, biceps and extensor carpi radial muscle reflexes, atrophy of the muscles triceps, biceps, extensor carpi radial, supraspinatus and infraespinatus; superficial skin sensorial loss distal to the elbow; dorsal carpal skin abrasions and ulceration. The association of these results with histologic and electroneurostimulation exams (described in part 2 and 3 of this work respectively) suggested in all cases an almost total involvement of brachial plexus roots.

Avulsão do plexo braquial em cães - 2: biópsia fascicular e histologia dos nervos radial, mediano, ulnar e musculocutâneo / Brachial plexus avulsion in dogs - 2: fascicular biopsy and histology of the radial, median, ulnar and musculocutaneous nerves

O objetivo deste trabalho foi demonstrar os aspectos clínicos e neurológicos relevantes para o diagnóstico da avulsão do plexo braquial em cães, relacionando estes achados com os resultados da histologia dos nervos radiais, medianos, ulnar e músculo cutânea. A biópsia fascicular destes nervos foi realizada após abordagem cirúrgica às faces lateral e medial do braço afetado. Todos os fascículos submetidos ao exame histológico apresentaram alterações como tumefação axonal, degeneração walleriana e infiltrado inflamatório em graus variados, havendo principalmente nos nervos radial, mediano e ulnar a proliferação de colagem endoneural. A associação destes resultados com as alterações neurológicas e da eletroneuroestimulação (relatados na parte 1 e 3 deste trabalho respectivamente) sugeriu envolvimento quase que total das raízes do plexo braquial em todos os casos.

The main purposes of this work were the neurological evaluation of dogs with brachial plexus avulsion and correlation of these findings with the results of histology of the radial, median, and ulnar and muscle cutaneous nerves. Fascicular nerve biopsy was performed after surgical approach of medial and lateral aspect of the arm. Ali the submitted fascicles presented histologic alterations compatible with wallerian degeneration, axonal swelling, and inflammatory infiltrate ranging from mild to pronounced, with endoneural collagen proliferation mainly in radial, median and ulnar nerves. The association of these results with neurological and electroneurostimulation exams (respectively described in part 1 and 3 of this work) suggested in all cases an almost total involvement of brachial plexus roots.

Avulsão do plexo braquial em cães - 3: eletroneuroestimulação dos nervos radial, mediano, ulnar e musculocutâneo / Brachial plexus avulsion in dogs - 3: electroneurostimulation of radial, median, ulnar and musculocutaneous nerves

O objetivo deste trabalho foi relacionar os aspectos clínicos, neurológicos e histopatológicos (descritos nas partes l e 2 deste trabalho) com os resultados obtidos após estimulação elétrica dos nervos radiai, mediano, ulnar e musculocutâneo. Realizou-se a estimulação elétrica destes nervos durante o ato cirúrgico no qual foram coletados os fascículos para histopatolo gia. Os nervos radial, mediano e ulnar de todos os cães submetidos à eletroneuroestimulação apresentaram evidências de degenera- ção. enquanto que o nervo musculocutâneo apresentava função próxima do normal em 25 por cento dos casos. A associação dos resultados do exame neurológico, da histologia e da eletroneuroestimulação sugeriu envolvimento quase que total das raízes do plexo braquial, enfatizando a necessidade de continuidade de pesquisas na área, visando principalmente a recuperação das raízes nervosas envolvidas.

The purpose ofthis work was to relate lhe clinicai, neurological and histopathotogical aspects (as described in the sections I and 2 ofthis work) with the obtained results after the electric stimulation of radial, median, ulnar and musculocutaneous nerrves. The electric stimulation of these nerves was realized during the cirurgic act, when the fascicle were obtained for the histopathologic examination. The radial, median and ulnar nerves of ali dogs submitted to electroneurostimulation presented evidences of degeneration, while the musculocutaneous nerve present almost normal functions in 25 percent of the cases. The interpretation ofthe results obtained from neurologic, histologic and electroneurostimulation examination suggested the almost total involvement of brachial plexus in ali cases. This work emphasized the need for further research in this área with lhe main purpose of recuperating the involved roots.

Dorsal Root Eentry Zone Operation for Brachial Plexus Avulsion Pain

No abstract available.