The thermal and mechanical anti-hyperalgesic effects of pre- versus post-intrathecal treatment with lamotrigine in a rat model of inflammatory pain

Intrathecal (IT) lamotrigine, a sodium channel blocker which suppresses neuronal release of glutamate, has been shown to produce a long-lasting antihyperalgesic effect in the neuropathic pain models. In the present study, we examined the anti-hyperalgesic effects of pre- versus post-treatment of IT lamotrigine in an animal inflammatory pain model, the inflamed knee joint model of the rat. Thermal and mechanical antinociception was assessed in rats using a modified Hargreaves box and von Frey hairs. Induction of tonic persistent inflammatory pain was induced by intra-articular injection (i.a.) of a carrageenan-kaolin mixture (CK) into the right knee-joint. Rats were randomly assigned to the groups receiving IT lamotrigine in distinct doses of 5, 50 or 100 ug either pre- (10 min before CK injection) or post-inflammation induction (4 h or 23 h). We observed that CK injection resulted in a significant thermal and mechanical hyperalgesia throughout a 24-h observation period. Pre-treatment with IT lamotrigine revealed a time and dose-dependent suppression of thermal and mechanical hyperalgesia, whereas the post-treatment with IT lamotrigine only showed an effect for mechanical nociception. Conclusion: IT Lamotrigine is antihyperalgesic at a dose larger than 50 ug in the early phase of inflammatory pain model. It reverses tactile allodynia but not thermal hyperalgesia when given after the inflammation induction. (C) 2002 Elsevier Science Inc. All rights reserved.