C. Advokat et al., Dissociation of (-) baclofen-induced effects on the tail withdrawal and hindlimb flexor reflexes of chronic spinal rats, PHARM BIO B, 63(4), 1999, pp. 527-534
We previously reported that the antinociceptive effect of the GABA(B) recep
tor agonist, (-)baclofen, in chronic spinal rats depended on the route of a
dministration. That is, subcutaneous (SC) injections significantly increase
d the latency of the thermally elicited tail withdrawal (tail flick, TF) re
flex, whereas spinal (intrathecal, IT) injections did not. The present stud
ies attempted to determine the reason for this differential response. The p
ossible contribution of a peripheral component to the systemic effect was e
valuated, but was not supported by negative results of intradermal (-)baclo
fen injections (50 and 500 mu g) into the tail skin of chronic spinal rats.
A spinal site of action was indicated when pretreatment with 30 mu g, IT o
f the GABA(B) receptor antagonist, phaclofen, significantly reduced the ant
inociceptive effect of SC (-)baclofen in both chronic spinal (5 mg/kg) and
intact rats (2 mg/kg). Moreover, direct IT injections of (-)baclofen in chr
onic spinal rats produced a modest, but statistically significant increase
in TF latency at doses of 0.06, 0.12, 0.3, and 0.6 mu g, but not 1.2 mu g.
In the same spinal preparation, the flexor response was significantly reduc
ed by IT injection of 0.6 and 1.2 mu g, but not lower doses of 0.3 and 0.12
mu g. These results provide the first quantitative, electrophysiological e
vidence of an antispastic effect of IT (-)baclofen in an in vivo, unanesthe
tized animal model. Second, the data show a separation between an antinocic
eptive effect of low spinal doses and an antispastic/muscle relaxant effect
at higher doses, which may account for the results of our prior report. Fi
nally, the data are also consistent with behavioral reports of antiallodyni
c/analgesic effects of low-dose baclofen, and may be relevant to the electr
ophysiological evidence of a preferential presynaptic action of low-dose (-
)baclofen at the primary afferent synapse. (C) 1999 Elsevier Science Inc.