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Vol. 282, Issue 3, 1242-1246, 1997
Department of Biology, Parke-Davis Neuroscience Research Centre,
Cambridge University Forvie Site, Cambridge, CB2 2QB United Kingdom
Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant
agents that selectively interact with the 
2
subunit of voltage-dependent calcium channels. This report describes
the activities of these two compounds in a rat model of postoperative
pain. An incision of the plantaris muscle of a hind paw induced thermal
hyperalgesia and tactile allodynia lasting at least 3 days.
Postoperative testing was carried out using the plantar test for
thermal hyperalgesia and von Frey hairs for tactile allodynia. A single
s.c. dose of gabapentin, 1 h before surgery, dose-dependently
(3-30 mg/kg) blocked the development of allodynia and hyperalgesia
with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively.
The highest dose of gabapentin prevented development of hyperalgesia
and allodynia for 24 and 49 h, respectively. Similar
administration of S-(+)-3-isobutylgaba also dose-dependently
(3-30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia
with MED of 3 and 10 mg/kg, respectively. The highest dose of
S-(+)-3-isobutylgaba completely blocked development of both
nociceptive responses for 3 days. The administration of S-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery
also completely blocked the maintenance of hyperalgesia and allodynia,
but its duration of action was much shorter (3 h). The administration of morphine (1-6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little
effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the
treatment of postoperative pain.
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