The present study investigated the role of peripheral P2Xreceptors in inflammatory pain transmission in the orofacialarea in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220 to 280 g. Formalin (5%, 50 μL) andcomplete Freund's adjuvant (CFA, 25 μL) was appliedsubcutaneously to the vibrissa pad to produce inflammatorypain. TNP-ATP, a P2X2,2/3,4 receptor antagonist, or OX-ATP, aP2X7 receptor antagonist, was then injected subcutaneouslyat 20 minutes prior to formalin injection. One of theantagonists was administered subcutaneously at three daysafter CFA injection. The subcutaneous injection of formalinproduced a biphasic nociceptive behavioral response. Subcutaneouspretreatment with TNP-ATP (80, 160 or 240 μg)significantly suppressed the number of scratches in the secondphase produced by formalin injection. The subcutaneousinjection of 50 μg of OX-ATP also produced significantantinociceptive effects in the second phase. Subcutaneousinjections of CFA produced increases in mechanical andthermal hypersensitivity. Both TNP-ATP (480 μg) andOX-ATP (100 μg) produced an attenuation of mechanicalhypersensitivity. However, no change was observed in thermalhypersensitivity after the injection of either chemical.These results suggest that the blockade of peripheral P2Xreceptors is a potential therapeutic approach to the onset ofinflammatory pain in the orofacial area.