Thymoquinone (TQ), the bioactive compound found in black seed, possesses beneficial properties. In the present study, the effects of oral administration of TQ were investigated on acute corneal and orofacial pains in rats. To clarify the central mechanism of action, muscarinic cholinergic, cannabinergic 1 (CB1) and 5-hydroxytryptamine receptor antagonists were delivered into the 4^th ventricle of the brain after oral administration of TQ. Acute corneal and orofacial pains were induced by dropping of hypertonic saline (50.00 µL; 5.00 M) on the corneal surface and subcutaneous injection of capsaicin (1.50 µg; 20.00 µL) in the vibrissal pad, respectively. The eye wiping number and face rubbing duration were recorded as corneal and orofacial pains behavioral responses, respectively. Locomotor activity was measured using an open-field test. The TQ (5.00 mg kg^-1) had no effects, while it reduced pain responses at 10.00, 20.00, and 40.00 mg kg^-1. Intracerebro-ventricular injections of naloxone (an antagonist of opioid receptors), (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (an antagonist of CB1 receptors), atropine (an antagonist of muscarinic cholinergic receptors), and ondansetron (an antagonist of 5-hydroxytryptamine 3 receptors) at a similar dose of 10.00 µg kg^-1 inhibited corneal and orofacial pains suppression caused by 40.00 mg kg^-1 TQ. The tested drugs did not affect locomotor activity. It is concluded that TQ caused analgesia in the acute corneal and orofacial pains. Central opioid, cholinergic muscarinic, CB1, and 5-hydroxytryptamine 3 receptors might be involved in the anti-nociceptive effects of TQ.