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Involvement of P2X 2 and P2X 3 receptors in neuropathic pain in a mouse model of chronic constriction injury
Author(s) -
Ueno Shinya,
Moriyama Tomoko,
Honda Kenji,
Kamiya Hiroo,
Sakurada Tsukasa,
Katsuragi Takeshi
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10208
Subject(s) - ppads , neuropathic pain , allodynia , hyperalgesia , nociception , pharmacology , receptor , anesthesia , medicine , nerve injury , chemistry , purinergic receptor
In the present study, we examined the involvement of P2X receptors in neuropathic pain using the chronic constriction injury (CCI) model. The thermal and mechanical nociceptive thresholds were evaluated using the paw withdrawal test and a von Frey test, respectively. Also, the expression of P2X receptors in the dorsal root ganglia (DRG) was analyzed using quantitative real‐time RT‐PCR. In the acute stage of CCI (3–30 days after injury), thermal hyperalgesia and mechanical allodynia had developed and mRNA of P2X 2 and P2X 3 was upregulated in the ipsilateral DRG. The thermal hyperalgesia at 7 days was inhibited by intrathecal (i.t.) administration of P2X antagonists, pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulfonate (PPADS), 2′‐O‐(trinitrophenyl)adenosine 5′‐triphosphate, trisodium salt (TNP‐ATP) and diinosine pentaphosphate (IP 5 I). In contrast, mechanical allodynia (7 days) was inhibited by the i.t. administration of PPADS and TNP‐ATP but not IP 5 I. These pharmacological and gene expression data suggest that upregulated homomeric P2X 3 and heteromeric P2X 2 and P2X 3 (P2X 2/3 ) receptors augmented thermal hyperalgesia and mechanical allodynia, respectively, at the spinal level in acute stage of CCI. In the chronic stage (>40 days), thermal hyperalgesia disappeared but the mechanical allodynia persisted. Only P2X 3 mRNA was downregulated. PPADS and TNP‐ATP failed to restore the mechanical threshold to the normal level. These data suggest that the involvement of P2X receptors changed in the chronic stage of CCI. Drug Dev. Res. 59:104–111, 2003. © 2003 Wiley‐Liss, Inc.