Behavioral and pharmacological characterization of a distal peripheral nerve injury in the rat

Abstract

Previous rat neuropathic pain models have utilized peripheral nerve injuries that damage a significant proportion of large nerves such as the sciatic nerve or its divisions. Injuries that lead to neuropathic pain in humans may involve the peripheral extremities. The current study evaluated the behavioral effects of injury to the plantar nerves in the rat (distal nerve injury-DNI). A delayed onset of hypersensitivity to an innocuous mechanical stimulus was observed following cutting of the left plantar nerves, whereas mechanical hypersensitivity developed more rapidly in rats with either an injury near the sciatic nerve trunk (chronic constriction injury (CCI), spared nerve injury (SNI)) or a spinal nerve root (spinal nerve ligation (SNL). Similar to other nerve injury pain models, rats with injured plantar nerves also developed an early onset and persistent sensitivity to a cooling stimulus. The effects of morphine, gabapentin and imipramine on mechanical and cold hypersensitivity were evaluated in rats with a DNI, CCI and SNI. In all three models, morphine dose-dependently suppressed mechanical and cold hypersensitivity, whereas gabapentin only suppressed mechanical hypersensitivity. Imipramine had no effect on either cold or mechanical hypersensitivity in any of the nerve-injured rats. The pharmacological data suggest that the underlying basis of neuropathic pain may be similar irrespective of the site of nerve injury.