Pharmacological characterisation of the spared nerve injury model of neuropathic pain

Abstract

The spared nerve injury (SNI) model involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the sural nerve intact. The changes in pain-like sensation of the injured animals appear to correlate with a number of symptoms presented in human patients with neuropathic pain syndromes. In order to characterise the SNI model pharmacologically, reflex nociceptive responses to mechanical and cold stimulation were measured after systemic administration of morphine, mexiletine, gabapentin and the glutamate receptor antagonists, MK-801 and NS1209. We observed that injection of morphine (6 mg/kg, s.c.) in non-sedative doses significantly attenuated mechanical hypersensitivity in response to von Frey hair and pin prick stimulation and cold hypersensitivity in response to ethyl chloride. The sodium-channel blocker, mexiletine (37.5 mg/kg, i.p.), relieved both cold allodynia and mechanical hyperalgesia, but the most distinct and prolonged effect was observed on mechanical allodynia. Gabapentin (100 mg/kg, i.p.) significantly alleviated mechanical allodynia for at least 3 h, while no significant effects were observed for either mechanical hyperalgesia or cold allodynia. In contrast, the NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) and the AMPA receptor antagonist NS1209 (6 mg/kg, i.p.) did not relieve any of the pain-like behaviours of the SNI animals. The present study has shown that a variety of drugs with proven analgesic potency in other models of chronic pain, have differing analgesic profiles in the SNI model of neuropathic pain.