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Novel method for restoration of anorectal function following spinal cord injury via nerve transfer in rats.

ABSTRACT: OBJECTIVES:Nerve transfer has been developed to restore partial function after serious nerve injuries, for example, restoring bladder control after spinal cord injury (SCI). Our aim here was to establish a preclinical proof-of-concept model using nerve transfer for restoring anorectal function after SCI. SETTING:We used laminectomy to model SCI, and bilateral spinal ventral and dorsal nerve root anastomosis to re-establish connectivity to the anorectal musculature. METHODS:Multidisciplinary methods were used to assess the anatomical and functional integrity of the alternative spinal-to-anorectal nerve circuit. Adult rats were used to establish the model. Bilateral anterior and posterior L5 nerve roots were surgically matched with anterior and posterior of S1 nerve roots by microscopic anastomosis to establish an artificial rectal reflex arc with complete sensory and motor pathways. Twelve weeks later, we used retrograde nerve tracing and neurohistomorphological analysis to assess anatomical integrity of the new artificial rectal reflex arc. Anorectal manometry was used to assess the function of the new nerve circuit. RESULTS:Retrograde tracing with recombinant attenuated pseudo rabies virus indicated that the new neural pathway was successfully established to the anorectal musculature after experimental SCI. Toluidine blue-stained sections of the anastomosis site revealed normal-appearing nerve fiber morphology and regeneration, and transmission electron microscopy revealed myelinated axons. Anorectal manometry revealed significant anorectal functional recovery. CONCLUSION:These results suggest that our model is a feasible first step in developing an alternative reflex pathway after laminectomy at L4 to S2 and shows promise for effective restoration of anorectal function.

SUBMITTER: Bao B

PROVIDER: S-EPMC7054926 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Novel method for restoration of anorectal function following spinal cord injury via nerve transfer in rats.

Bao Bingbo B Fu Kai K Zheng Xianyou X Wei Haifeng H Luo Pengbo P Zhu Hongyi H Zhu Xiaozhong X Li Xingwei X Gao Tao T

The journal of spinal cord medicine 20180306 2

<h4>Objectives</h4>Nerve transfer has been developed to restore partial function after serious nerve injuries, for example, restoring bladder control after spinal cord injury (SCI). Our aim here was to establish a preclinical proof-of-concept model using nerve transfer for restoring anorectal function after SCI.<h4>Setting</h4>We used laminectomy to model SCI, and bilateral spinal ventral and dorsal nerve root anastomosis to re-establish connectivity to the anorectal musculature.<h4>Methods</h4> ...[more]

PMID: 29509106

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Project description:BackgroundThe aim of this study is to clarify the neural mechanisms underlying orofacial pain abnormalities after cervical spinal nerve injury. Nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK) expression and astroglial cell activation in the trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal dorsal horn (C1-C2) neurons were analyzed in rats with upper cervical spinal nerve transection (CNX).ResultsThe head withdrawal threshold to mechanical stimulation of the lateral facial skin and head withdrawal latency to heating of the lateral facial skin were significantly lower and shorter respectively in CNX rats compared to Sham rats. These nocifensive effects were apparent within 1 day after CNX and lasted for more than 21 days. The numbers of pERK-like immunoreactive (LI) cells in superficial laminae of Vc and C1-C2 were significantly larger in CNX rats compared to Sham rats following noxious and non-noxious mechanical or thermal stimulation of the lateral facial skin at day 7 after CNX. Two peaks of pERK-LI cells were observed in Vc and C1-C2 following mechanical and heat stimulation of the lateral face. The number of pERK-LI cells in C1-C2 was intensity-dependent and increased when the mechanical and heat stimulations of the face were increased. The decrements of head withdrawal latency to heat and head withdrawal threshold to mechanical stimulation were reversed during intrathecal (i.t.) administration of MAPK/ERK kinase 1/2 inhibitor PD98059. The area of activated astroglial cells was significantly higher in CNX rats (at day 7 after CNX). The heat and mechanical nocifensive behaviors were significantly depressed and the number of pERK-LI cells in Vc and C1-C2 following noxious and non-noxious mechanical stimulation of the face was also significantly decreased following i.t. administration of the astroglial inhibitor fluoroacetate.ConclusionsThe present findings have demonstrated that mechanical allodynia and thermal hyperalgesia occur in the lateral facial skin after CNX and also suggest that ERK phosphorylation of Vc and C1-C2 neurons and astroglial cell activation are involved in orofacial extraterritorial pain following cervical nerve injury.

Dataset Information

Novel method for restoration of anorectal function following spinal cord injury via nerve transfer in rats.

Publications

Novel method for restoration of anorectal function following spinal cord injury via nerve transfer in rats.

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