At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord

Abstract

Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. We examined whether a unilateral L6-S1 ventral root avulsion (VRA) injury in adult female rats might elicit pain within the dermatome projecting to the adjacent, uninjured L5 spinal segment. Additionally, a subset of subjects had the avulsed L6-S1 ventral roots reimplanted (VRA+Imp) into the lateral funiculus post-avulsion to determine whether this neural repair strategy elicits or ameliorates pain. Behavioral tests for mechanical allodynia and hyperalgesia were performed weekly over 7 weeks post-injury at the hind paw plantar surface. Allodynia developed early and persisted post-VRA, whereas VRA+Imp rats exhibited allodynia only at 1 week postoperatively. Hyperalgesia was not observed at any time in any experimental group. Quantitative immunohistochemistry showed increased levels of inflammatory markers in laminae III-V and in the dorsal funiculus of the L5 spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive projections from mechanoreceptive, but not nociceptive, primary afferents. These data suggest that sustained at-level neuropathic pain can develop following a pure motor lesion, whereas the pain may be ameliorated by acute root reimplantation. We believe that our findings are of translational research interest, as root implantation surgery is emerging as a potentially useful strategy for the repair of cauda equina/conus medullaris injuries.

Re-established micturition reflexes show differential activation patterns after lumbosacral ventral root avulsion injury and repair in rats

“…However, we have recently developed a rat lumbosacral ventral root avulsion (VRA) injury model, which mimics key features of the clinical CM syndrome, including denervation of pelvic targets and the development of neuropathic pain (Hoang et al, 2003(Hoang et al, , 2006aBigbee et al, 2007). A bilateral L5-S2 VRA injury in the rat is followed by urinary retention and absence of both reflex bladder contractions and EUS activity detected by electromyography (EMG), as well as increased bladder weight and size (Hoang et al, 2006a).…”

Minocycline protects motor but not autonomic neurons after cauda equina injury

“…Minocycline may also attenuate the development of hyperesthesia and allodynia after an L5 spinal nerve transection injury in the rat (Raghavendra et al, 2003). The latter finding is of special interest to the present studies, as both transection and avulsion injuries of ventral roots may result in persistent neuropathic pain Bigbee et al, 2007). However, in some studies, minocycline treatment has failed to demonstrate beneficial effects (Smith et al 2003;Fernandez-Gomez et al 2005).…”

Reimplantation of avulsed lumbosacral ventral roots in the rat ameliorates injury-induced degeneration of primary afferent axon collaterals in the spinal dorsal columns

“…As such, we showed that a unilateral L6-S1 VRA injury induces at-level allodynia, concomitant with glial and macrophage activation in the adjacent L5 deep dorsal gray matter and dorsal funiculus (DF) ipsilateral to the lesion at 8 weeks post-injury (Bigbee et al, 2007). Importantly, acute reimplantation of the avulsed lumbosacral roots into the lateral funiculus ameliorated VRAinduced neuropathic pain and inflammation in the dorsal horn (Bigbee et al, 2007). The regions of specificity of the inflammatory response in the dorsal horn of the VRA group warrants further investigation.…”

“…Experimental groups included: 1) sham operated controls receiving a hemi-laminectomy (Lam; n=7); 2) rats receiving unilateral avulsion of the L6-S1 ventral roots (VRA; n=9); and 3) rats undergoing unilateral L6-S1 VRA followed by immediate implantation of the avulsed roots into the lateral funiculus (Imp; n=5). The surgical procedures for the unilateral VRA procedure have been previously described (Bigbee et al, 2007). Briefly, a midline incision was made over the lumbar spine under anesthesia (2% isoflurane), and an L1-3 hemi-laminectomy was performed.…”