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.


CONCLUSIONS
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.
Lee
Tsung-Hsing
TH
Anesthesiology Research Laboratory, Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, 123 Ta-Pei Road, Niao Shung Hsiang, Hsien, 833, Kaohsiung, Taiwan.
Wang
Ching-Jen
CJ
Wu
Ping-Ching
PC
Buerkle
Hartmut
H
Lin
S-H
SH
Yang
Lin-Cheng
LC
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007278:Injections, Spinal; D007719:Knee Joint / Q000503:physiopathology; D000077213:Lamotrigine; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D011897:Random Allocation; D051381:Rats; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D014227:Triazines; D000077213:Lamotrigine