Intrathecally administered gabapentin inhibits formalin-evoked nociceptionand the expression of Fos-like immunoreactivity in the spinal cord of the rat
M. Kaneko et al., Intrathecally administered gabapentin inhibits formalin-evoked nociceptionand the expression of Fos-like immunoreactivity in the spinal cord of the rat, J PHARM EXP, 292(2), 2000, pp. 743-751
Citations number
38
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
In the present study, we investigated the effects of intrathecal gabapentin
on nociceptive behaviors and the numbers of spinal Fos-like immunoreactive
(Fos-LI) neurons evoked by injection of 0.25 to 2.5% formalin in the hindp
aw of the rat. Pretreatment with gabapentin dose dependently decreased flin
ches and weighted pain scores in phase 2, but not phase 1, at each concentr
ation of formalin. The highest dose of gabapentin (100 mu g) shifted the EC
50 values of formalin for both flinches and weighted pain scores to the rig
ht by 2.5-fold, suggesting that formalin was perceived to be significantly
less noxious. Gabapentin also decreased phase 2 behaviors when administered
after formalin but was only one third as potent. Unlike its inhibition of
formalin-evoked nociceptive behaviors, the effect of gabapentin on the expr
ession of Fos-like immunoreactivity in the spinal cord was highly dependent
on the concentration of formalin. Intrathecal pretreatment with 100 mg of
gabapentin did not decrease the numbers of Fos-LI neurons evoked by 0.5% fo
rmalin, yet this dose decreased the numbers of Fos-LI neurons in laminae I-
II and VII-X of rats that received 1.25% formalin and uniformly decreased b
y 50% the numbers of Fos-LI neurons in all laminae of rats that received 2.
5% formalin. These latter findings suggest that gabapentin neither nonselec
tively decreases the excitability of spinal cord neurons nor uniformly inhi
bits the release of all neurotransmitters from primary afferent terminals.
Rather, its effects may be preferential for those neurotransmitters release
d by higher, more noxious concentrations of formalin and for conditions in
which there is a greater induction of central sensitization.