Role Of Selected Muscarinic, Nicotinic And Opioidergic Drugs In Pain Regulation In The Tachyoryctes Splendens.

Abstract

Little is known about nociception in the East African root rat Tachyoryctes splendens. This therefore prompted further exploration of nociception and antinociception in this species with specific attention to pain modulation by the cholinergic and opioidergic neurotransmitter systems. Three nociceptive tests, namely the formalin-, tail flick-, and the acetic acid induced writhing tests were used to study the nociceptive and antinociceptive effects of selected cholinergic (oxotremorine-muscarinic receptor agonist and epibatidine-nicotinic receptor agonist) and opioidergic drugs (morphine-µ-receptor agonist). Oxotremorine (10, 20, and 60 µg/kg dose levels), epibatidine (1, 3 and 10 µg/kg dosage levels) and morphine (1, 3, and 6 mg/kg dosage levels) were administered systemically. Atropine, mecamylamine and naloxone which are their respective blockers were used for antagonistic reactions. A total of one hundred and twenty East African root rats were used in the experiments. In the formalin test, a monophasic (0-5 minutes) pain behavioral response characterized by biting, licking and favoring of the injected limb was observed. The behavioural response in the late phase (> 5 Minutes) was insignificantly different (P ≥ 0.05) from that of the controls. Oxotremorine at the selected doses (30 or 60 µg/kg) induced a statistically significant (P ≤ 0.05) dose-dependent reduction in the mean time spent licking/biting the injected paw in the early phase of the formalin test. The median effective dose was 21 µg/kg. The effect of oxotremorine (30 µg/kg), on the mean time spent licking/biting the injected paw was reversed by atropine. Epibatidine (3 or 10 µg/kg) caused a statistically significant (P ≤ 0.05) reduction in the mean time spent in licking/biting the injected paw in the formalin test. The median effective dose was 4.5 µg/kg. Co-administration of mecamylamine with epibatidine (3 µg /kg), significantly increased the mean time spent in licking/biting the injected paw. Morphine (3 or 6 mg/kg) caused a statistically significant (P ≤ 0.05) decrease in the mean licking/biting response. The mean effective dose was 4.5 mg/kg. The effect of morphine (3 mg/kg) was reversed by the administration of naloxone (2.5 mg/kg). Lower doses of oxotremorine, epibatidine and morphine had no effect on the mean licking/biting behaviour. In the tail flick test, with a sensitivity setting of 10, beam at 8 and a cut-off time of 10 seconds, no tail flick was observed even after increasing the cut off period to 20 seconds. The acetic acid induced writhing test also did not cause any observable nociceptive behavior. In conclusion, the present data uniquely showed that the formalin test induces a monophasic pain behavior in the East African root rat and secondly, this species appears to have a functional nociceptive system sensitive to cholinergic and opioidergic analgesics.