A comparison of the anti-nociceptive effects of voltage-activated Na+ channel blockers in the formalin test.
We have used the rat formalin test to compare the anti-nociceptive properties of several voltage-activated Na(+) channel blockers. The antiarrhthymic mexiletine (37.5 and 50 mg/kg, i.p.) attenuated flinching behaviour in both first and second phases of the test compared with vehicle (P<0.05). The anti-convulsants lamotrigine (15 and 30 mg/kg, i.p.) and carbamazepine (20 mg/kg, i.p.) also inhibited second phase flinching behaviour compared with vehicle (P<0.05), although phenytoin (up to 40 mg/kg, i.p.) was without effect. Riluzole (5 mg/kg, i.p.), in contrast to lubeluzole (up to 10 mg/kg, i.p.) also inhibited second phase flinching behaviour compared with vehicle (P<0.05). When tested against an acute thermal nociceptive stimulus mexiletine, lubeluzole and riluzole exhibited anti-nociceptive effects. The anti-nociceptive doses used in the formalin test produced no motor impairment in the rotarod test. Thus, voltage-activated Na(+) channel blockers can attenuate nociceptive behaviour in the formalin test, and a specific mechanism of action on Na(+) channel function may be required for this to occur.
Blackburn-Munro
Gordon
G
Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750, Ballerup, Denmark. gbm@neurosearch.dk
Ibsen
Nete
N
Erichsen
Helle K
HK
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*
D000700:Analgesics; D026941:Sodium Channel Blockers; D015222:Sodium Channels