Abstract: The anti-nociceptive effect of melatonin on visceral pain evoked by i.p. acetic acid injection in mice was investigated. Melatonin (1-8 mg kg-1, s.c.) caused a dose-dependent inhibition of the acetic acid-induced writhes (by 84 to 98.6%). The inhibition of writhing response by melatonin (4 mg kg-1) was not reduced by co-administration of theα-2 adrenoceptor antagonist yohimbine (4 mg kg-1, i.p.). In contrast, the α-1 adrenoceptor antagonist doxazocin (16 mg kg-1, s.c.) reduced the anti-writhing effect of melatonin, whereas the α 1-adrenoceptor antagonist prazosin (2 mg kg-1, i.p.) was without effect. The effect of melatonin was slightly reduced by beta-adrenoceptor blockade with propranolol (2 mg kg-1, i.p.) or adrenergic neuron blockade with guanethidine (8 or 16 mg kg-1, i.p.). The muscarinic receptor antagonist atropine (2 mg kg-1 i.p.), the potassium channel blocker glibenclamide (5 mg kg-1, i.p.), the opioid antagonist naloxone (5 mg kg-1, i.p.) or the non-selective adenosine receptor antagonist, theophylline (10 mg kg-1 i.p.), failed to reduce the anti-writhing effect of melatonin. The antinociceptive effect of melatonin was slightly reduced by co-administration of the central dopamine D2 receptor antagonist sulpiride (15 mg kg-1, i.p.) (though not by haloperidol, 2 mg kg-1, i.p.) and to more extent by the dopamine D2 receptor agonist bromocryptine (1.5 mg kg-1, i.p.), whereas metoclopramide (3 mg kg-1, i.p.), chlorpromazine (3 mg kg-1, i.p.), domperidone (10 mg kg-1, i.p.) or blockade of dopamine D1 receptors by clozapine (5 mg kg-1, i.p.) had no effect. In conclusion, melatonin exerts potent anti-nociceptive effects on visceral pain in mice. The antinociception caused by melatonin is subject to modulation by noradrenergic and dopaminergic neural pathways.