Antinociceptive effects of the ORL1 receptor agonist nociceptin/orphanin FQ in diabetic mice

The antinociceptive potency of nociceptin/orphanin FQ, an opioid-like orpha n receptor agonist, was examined using the tail-flick test and the formalin -induced nociception test in diabetic mice. Nociceptin/orphanin FQ, at dose s of 0.1 to 10 nmol, intrathecal (i.t.), produced a marked and dose-depende nt inhibition of the tail-flick response in both non-diabetic and diabetic mice. The antinociceptive effect of nociceptin/orphanin FQ in the tail-flic k test in diabetic mice was greater than that in non-diabetic mice. The ant inociceptive effect of nociceptin/orphanin FQ was not antagonized by pretre atment with either beta-funaltrexamine, a selective mu-opioid receptor anta gonist, naltrindole, a selective delta-opioid receptor antagonist, or nor-b inaltorphimine, a selective kappa-opioid receptor antagonist. The antinocic eptive effects of nociceptin/orphanin FQ in diabetic, but not in non-diabet ic mice, were abolished when mice were pretreated with capsaicin i.t. 24 h before testing. In the formalin test, nociceptin/orphanin FQ also produced a marked and dose-dependent antinociceptive effect on the first-phase respo nse, but not the second phase-response, in both diabetic and non-diabetic m ice. Furthermore, nociceptin/orphanin FQ significantly and dose-dependently reduced the flinching responses to i.t.-administered substance P in diabet ic mice, but not in non-diabetic mice. The results of the present experimen ts clearly indicate that the antinociceptive potency of nociceptin/orphanin FQ is significantly greater in diabetic mice than in non-diabetic mice. Fu rthermore, the results of this study suggest that the reduction of substanc e P-mediated nociceptive transmission in the spinal cord may be responsible for the antinociceptive effect of nociceptin/orphanin FQ. (C) 1999 Elsevie r Science B.V. All rights reserved.