Participation of Central P2X7 Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats
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We investigated the role of central P2X receptors ininflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawleyrats weighing 230-280g. Complete Freund's adjuvant (CFA,40 μL) was applied subcutaneously to the vibrissa pad toproduce inflammatory pain. The intracisternal administrationof iso-PPADS tetrasodium salt, a non-selective P2X receptorantagonist, A317491 sodium salt hydrate, a P2X2/3 receptorantagonist, 5-BDBD, a P2X4 receptor antagonist, or A438079hydrochloride, a P2X7 receptor antagonist, was performed 5days after CFA injection. Subcutaneous injections of CFAproduced increases in thermal hypersensitivity. Intracisternalinjections of iso-PPADS (25 μg) or A438079 (25 or 50 μg)produced significant anti-hyperalgesic effects against thermalstimuli compared to the vehicle group. A317491 or 5-BDBDdid not affect the head withdrawal latency times in ratsshowing an inflammatory response. Subcutaneous injectionsof CFA resulted in the up-regulation of OX-42, a microgliamarker, and GFAP, an astrocyte marker, in the medullarydorsal horn. The intracisternal administration of A438079reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that ablockade of the central P2X7 receptor produces antinociceptiveeffects, mediated by inhibition of glial cellfunction in the medullary dorsal horn. These data also indicatethat central P2X7 receptors are potential targets for futuretherapeutic approaches to inflammatory pain in the orofacialarea.
Abstract
We investigated the role of central P2X receptors ininflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawleyrats weighing 230-280g. Complete Freund's adjuvant (CFA,40 μL) was applied subcutaneously to the vibrissa pad toproduce inflammatory pain. The intracisternal administrationof iso-PPADS tetrasodium salt, a non-selective P2X receptorantagonist, A317491 sodium salt hydrate, a P2X2/3 receptorantagonist, 5-BDBD, a P2X4 receptor antagonist, or A438079hydrochloride, a P2X7 receptor antagonist, was performed 5days after CFA injection. Subcutaneous injections of CFAproduced increases in thermal hypersensitivity. Intracisternalinjections of iso-PPADS (25 μg) or A438079 (25 or 50 μg)produced significant anti-hyperalgesic effects against thermalstimuli compared to the vehicle group. A317491 or 5-BDBDdid not affect the head withdrawal latency times in ratsshowing an inflammatory response. Subcutaneous injectionsof CFA resulted in the up-regulation of OX-42, a microgliamarker, and GFAP, an astrocyte marker, in the medullarydorsal horn. The intracisternal administration of A438079reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that ablockade of the central P2X7 receptor produces antinociceptiveeffects, mediated by inhibition of glial cellfunction in the medullary dorsal horn. These data also indicatethat central P2X7 receptors are potential targets for futuretherapeutic approaches to inflammatory pain in the orofacialarea.
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