Int J Oral Biol.  2014 Mar;39(1):49-56.

Participation of Central P2X7 Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats

Affiliations
  • 1Department of Oral physiology, School of Dentistry, Kyungpook National University, Daegu (700-412), Korea. dkahn@knu.ac.kr

Abstract

We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, 40 microL) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a P2X2/3 receptor antagonist, 5-BDBD, a P2X4 receptor antagonist, or A438079 hydrochloride, a P2X7 receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS (25 microg) or A438079 (25 or 50 microg) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central P2X7 receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central P2X7 receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.

Keyword

P2X receptor; CFA; inflammation; thermal hyperalgesia; glia

MeSH Terms

Animals
Astrocytes
Freund's Adjuvant
Head
Horns
Humans
Hyperalgesia
Hypersensitivity
Inflammation
Injections, Subcutaneous
Male
Microglia
Neuroglia
Rats*
Rats, Sprague-Dawley
Receptors, Purinergic P2X4
Receptors, Purinergic P2X7*
Sodium
Up-Regulation
Freund's Adjuvant
Receptors, Purinergic P2X4
Receptors, Purinergic P2X7
Sodium
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