CLINICS 2011;66(2):321-325 Effect of glibenclamide on antinociceptive effects of antidepressants Hajhashemi V and Amin B Figure 1 - The antinociceptive effect of i.p. administration of amitriptyline and amitriptyline plus glibenclamide on licking behavior during phase 2 of formalin test. Bars are mean ¡ SEM for six animals. * means significantly different from control group (p,0.001) and # means significantly different from Ami5 group (p,0.05). phase two of formalin test that is in agreement with previous studies.3,5 As indicated, phase 2 of formalin test is due to central sensitization of inflammatory pathways. This kind of sensitization is a key mechanism in inducing chronic pain.26 These data support the beneficial effect of antidepressants in chronic pain conditions. Glibenclamide neither in phase 1 nor in phase 2 could attenuate pain behavior caused by formalin and this is in agreement with previous studies that showed the sulphonylurea drugs such as glibenclamide did not cause hyperalgesia or antinocicep- tion when administered alone.15,22 As it was mentioned in introduction, activation of G-protein coupled receptors by agonists such as a2-adrenoceptors, opioids, GABAB, mus- carinic M2, adenosine A1, serotonin 5-HT1A and cannabinoid receptors and some nonsteroidal anti-inflammatory drugs (NSAIDs) can activate K+ channels and this mechanism to some extent explains their antinociceptive effects.21 In the absence of analgesic drugs there is no activation of these Figure 2 - The antinociceptive effect of i.p. administration of fluvoxamine and fluvoxamine plus glibenclamide on licking behavior during phase 2 of formalin test. Bars are mean ¡ SEM for six animals. * means significantly different from control group (p,0.001) and # means significantly different from Fluv20 group (p,0.05). 323