Comparison of the anti-allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain

Abstract

The present study has assessed the efficacy and potency of systemic, intrathecal (i.t.) and intracerebroventricular (i.c.v.) morphine in alleviating a chronic mechanical allodynia-like behaviour in a rat model of central pain after spinal cord injury. The anti-allodynic potency of morphine was compared to its antinociceptive potency in both spinally injured and normal rats. Systemic (intraperitoneal or subcutaneous) morphine did not significantly relieve allodynia up to 3 mg/kg cumulative dose, which was sedative. Mechanical allodynia-like behaviour was only significantly relieved by l0 mg/kg morphine which caused severe sedation. Low doses of i.c.v. morphine abolished vocalization of allodynic rats to von Frey hair stimulation. However, other components of abnormal reactions to innocuous mechanical stimulation, such as agitation, jumping and avoidance, were only relieved by i.c.v. morphine at high, sedative doses. In contrast, i.t. morphine dose dependently reversed all components of the allodynic reactions without causing sedation. Morphine administered by all three routes produced powerful antinociception in the tail flick test in normal rats. The antinociceptive potency of morphine was reduced after systemic, i.t. and, particularly, i.c.v. administration in allodynic rats. These results indicated that i.t. morphine relieved the mechanical allodynia-like responses in spinally injured rats, whereas systemic or i.c.v. morphine only increased the response threshold to innocuous mechanical stimulation at high doses, which was associated with sedation, making it difficult to assess the anti-allodynic effect. However, i.c.v. morphine may be particularly effective for the affective component of pain in the present model. The antinociceptive potency of morphine was also reduced in spinally injured rats. It is suggested that morphine may be differentially effective against different types of pain after different routes of administration. Spinal morphine may be a therapeutic alternative in treating central pain after spinal cord injury.