Segmental Spinal Root Avulsion in the Adult Rat: A Model To Study Avulsion Injury Pain

Abstract

Road traffic accidents are the most common cause of avulsion injury, in which spinal roots are torn from the spinal cord. Patients suffer from a loss of sensorimotor function, intractable spontaneous pain, and border-zone hypersensitivity. The neuropathic pains are particularly difficult to treat because the lack of a well-established animal model of avulsion injury prevents identifying the underlying mechanisms and hinders the development of efficacious drugs. This article describes a hindlimb model of avulsion injury in adult rats where the L5 dorsal and ventral spinal root are unilaterally avulsed (spinal root avulsion [SRA]), leaving the adjacent L4 spinal root intact. SRA produced a significant ipsilateral hypersensitivity to mechanical and thermal stimulation by 5 days compared with sham-operated or naïve rats. This hypersensitivity is maintained for up to 60 days. No autotomy was observed and locomotor deficits were minimal. The hypersensitivity to peripheral stimuli could be temporarily ameliorated by administration of amitriptyline and carbamazepine, drugs that are currently prescribed to avulsion patients. Histological assessment of the L4 ganglion cells revealed no significant alterations in calcitonin gene-related peptide (CGRP), IB4, transient receptor potential cation channel subfamily V member 1 (TrpV1), or N52 staining across groups. Immunohistochemistry of the spinal cord revealed a localized glial response, phagocyte infiltration, and neuronal loss within the ipsilateral avulsed segment. A comparable response from glia and phagocytes was also found in the intact L4 spinal cord, supporting the role for central mechanisms within the L4-5 spinal cord in contributing to the generation of the pain-related behavior. The SRA model provides a platform to investigate possible new pharmacological treatments for avulsion injuries.

Boundary cap neural crest stem cells homotopically implanted to the injured dorsal root transitional zone give rise to different types of neurons and glia in adult rodents

“…The limated glial differentiation in the spinal cord in our study may be explained by the different environments in the immature SVZ and in conditions with pure de-/dysmyelination compared to the combination of axonal as well as myelin disintegration that occurs after dorsal root avulsion. Dorsal root avulsion also results in degeneration of second order neurons [30], extensive microglial, astroglial and vascular changes [31], processes which may provide additional stimuli for differentiation of bNCSCs towards neuronal phenotypes.…”

A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent

“…22 We observed significant at-level sensory alterations after clip impact-compression injury, which mimics similar outcomes seen in many lumbar root avulsion models. [35][36][37] Root avulsion models are designed to replicate the rare clinical scenario where the root is avulsed without an accompanying SCI. Many peripheral nerve injuries are mixed injuries including both a CNS spinal cord component and a PNS peripheral component, such as those seen in injuries to the thoracolumbar spinal cord at T10-T12 vertebral level.…”

Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

“…Many of these inputs project directly or indirectly to the motoneurons present in the ventral horn. Loss of sensorial information greatly affects motor behavior and constitutes an important medical problem (Rabert et al, 2004; Bigbee et al, 2007; Wu et al, 2012; Chew et al, 2013; Matsuura et al, 2013). …”

“…Due to this, a significant number of patients begin to obtain limited motor function recovery up to 1 year after surgery (Carlstedt, 2009). However, since the restoration of sensory functions does not occur (Carlstedt, 2009; Chew et al, 2013), a persistent imbalance of excitatory and inhibitory inputs remains and generates important changes in the CNS homeostasis.…”