role of ATP-sensitive K[+] channels in the antinociceptive effect of gabapentin and lamotrigine in rats

ABSTRACT

Persistent pain syndromes are considered by some to be poorly responsive to analgesics such as opioids and non-steroidal antiinflammatory drugs. There has been growing interest in the potential utility of anticonvulsant drugs in the treatment of persistent pain, but systematic studies comparing the various clinically used drugs have not been conducted. Was to investigate the analgesic effects of anticonvulsant drugs [gabapentin and lamotrigine] in a persistent pain model, the formalin test which shows injury-induced hyperalgesia as well as acute pain and the spinal reflex test, paw-pressure test. Also, to determine the participation of the ATP-sensitive K[+] channels in the antinociceptive effect of both drugs. Seventy two adult male albino rats were divided into 2 main groups, the formalin test [group I] and the paw pressure test [group II]. Each group was divided into 6 subgroups [6 rats each] Subgroup a rats served as the untreated control, whereas, Subgroup a rats were given intraperitoneal [i.p.] saline as a solvent of glibenclamide. Subgroups b and c rats received a single oral dose of gabapentin [300 mg/kg] or lamotrigine [100mg/kg], respectively, by gastric gavage. One hour later, rats were subjected to formalin test or paw pressure test. Subgroups d and e rats received glibenclamide in a dose of [0.5 mg/kg i.p], 15 minutes later, rats received either oral gabapentin or lamotrigine, respectively, in the same previously mentioned doses. One hour later, rats were subjected to formalin test or paw pressure test. A single oral dose of gabapentin [300 mg/kg] or lamotrigine [100 mg/kg] reduced the flinching behavior significantly in both the first and second phases of the formalin test. Moreover, gabapentin and lamotrigine significantly increased the paw withdrawal threshold. The selective blockers of ATP-sensitive K[+] channels glibenclamide [0.5 mg/kg i.p] partially antagonized the antinociception induced by gabapentin and lamotrigine both in formalin test and paw-pressure test. The results showed that a single oral dose of gabapentin or lamotrigine produced antinociceptive effects it both the formalin test and the paw pressure test. Intraperitoneal glibenclamide significantly attenuated the antinoceciptive effect of both drugs, suggesting that activation of ATP sensitive K[+] channels plays a role in the antinoceciptive effect of gabapentin or lamotrigine