Below Level Central Pain Induced by Discrete Dorsal Spinal Cord Injury

Abstract

Central neuropathic pain occurs with multiple sclerosis, stroke, and spinal cord injury (SCI). Models of SCI are commonly used to study central neuropathic pain and are excellent at modeling gross physiological changes. Our goal was to develop a rat model of central neuropathic pain by traumatizing a discrete region of the dorsal spinal cord, thereby avoiding issues including paralysis, urinary tract infection, and autotomy. To this end, dorsal root avulsion was pursued. The model was developed by first determining the number of avulsed dorsal roots sufficient to induce below-level hindpaw mechanical allodynia. This was optimally achieved by unilateral T13 and L1 avulsion, which resulted in tissue damage confined to Lissauer's tract, dorsal horn, and dorsal columns, at the site of avulsion, with no gross physical changes at other spinal levels. Behavior following avulsion was compared to that following rhizotomy of the T13 and L1 dorsal roots, a commonly used model of neuropathic pain. Avulsion induced below-level allodynia that was more robust and enduring than that seen after rhizotomy. This, plus the lack of direct spinal cord damage associated with rhizotomy, suggests that avulsion is not synonymous with rhizotomy, and that avulsion (but not rhizotomy) is a model of central neuropathic pain. The new model described here is the first to use discrete dorsal horn damage by dorsal root avulsion to create below-level bilateral central neuropathic pain.

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

“…Some models use complete deafferentation of the ipsilateral forepaw, [27][28][29][30] or a thoracic avulsion 31,57 to characterize bilateral pain in the hind paws. These two models do not represent avulsion pain as it is known in the clinic.…”

“…Current animal models of unilateral root avulsion injury produce specific pain syndromes in dermatomes far rostral or caudal to the segment of injury. [27][28][29][30][31] These are more representative models of ''belowlevel'' central pain that occurs clinically in conditions such as stroke, multiple sclerosis, and spinal cord injury rather than avulsion injury pain, because, as far as we are aware, these contralateral effects and pain at sites distant to injury do not occur in avulsion patients. The L6-S1 ventral root avulsion injury model 25 produces ipsilateral mechanical hypersensitivity in the L5 spinal cord.…”

“…However, rhizotomy models either fail to elicit reproducible behavioral hypersensitivity, 34,35 or produce transient pain depending on time points assessed. 31,36,37 Moreover, rhizotomy is a procedure that is often used to alleviate neuropathic pain. Most studies use rhizotomy (of either dorsal or ventral roots) in order to investigate techniques to promote functional recovery, CNS plasticity, or the effects of drugs on neuroprotection of motoneurons.…”

Morphine amplifies mechanical allodynia via TLR4 in a rat model of spinal cord injury

“…Our model, termed SNAP ( S pinal N europathic A vulsion P ain), creates physical damage to the superficial laminae of the sensory dorsal horn and robust, reliable, below-level bilateral hindpaw mechanical allodynia for ~9 weeks (Ellis et al, 2014; Wieseler et al, 2010). …”

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.…”