Investigation of the role of Z944 related to muscarinic receptors on hyperalgesia in rats.

Abstract

Background: This study aims to investigate the muscarinic receptor-associated Z944 responses on hyperalgesia resulting from chronic constriction injury (CCI) of the rat sciatic nerve.

Materials and methods: A total of 72 male Wistar Albino rats (200-250 g) were randomly divided into eight groups. The right sciatic nerve CCI of Wistar Albino rats was performed except the Saline intraperitoneal (i.p.) group. Two weeks after the operations, pressure test of both paws and hot plate test were performed in the groups of Saline, CCI + Saline, CCI + DMSO (i.p.), CCI + 1 mg/kg Atropine (i.p), CCI + Z944 1, 3, 10 mg/kg (i.p) dose and CCI + 1 mg/kg Atropine + 10 mg/kg Z944. The locomotor activity test was performed before the tests.

Results: The results of right paw pressure test (p < 0.001) and hot plate test (p = 0.032) of CCI + Saline group, compared to the Saline group test results, confirmed the development of mechanical hyperalgesia and thermal hyperalgesia of the CCI + Saline group. The locomotor activities of Saline and other CCI groups were higher than the activity of CCI + 1 mg/kg Atropine group (p = 0.017). The dose-dependent increasing effect of Z944 in dose groups compared to the CCI + Saline group was determined, respectively, in the right paw pressure test (p = 0.472, p = 0.006, p < 0.001) and the hot plate test (p = 0.001, p < 0.001, p < 0.001). The left paw pressure test results of CCI + Saline group and Z944 dose groups were not statistically different (p = 0.995, p = 0.159, p = 0.110, respectively). Also, there were no statistically differences between the CCI + Saline and the CCI + 1 mg/kg Atropine + 10 mg/kg Z944 groups according to right paw pressure (p = 0.945), left paw pressure (p = 0.763), and hot plate (p = 0.817) tests results.

Conclusion: The attenuation of the analgesic effect of Z944 by the non-selective muscarinic receptor antagonist atropine suggests that the analgesic activity of Z944 may be mediated, at least in part, through muscarinic receptor-dependent mechanisms.