HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice.

Abstract
1. The aim of the present study is to characterize the role of spinal endogenous ATP and P2X receptors in the generation of neurogenic and inflammatory pain. We examined the effects of intrathecal treatment with P2X receptor antagonists on the formalin- and capsaicin-induced nociceptive behaviours in mice. 2. Intrathecal pretreatment with the general P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS), significantly suppressed both the first and second phases of the formalin-induced nociceptive behaviour. The second phase of the nociceptive response was also suppressed by intrathecal treatment with PPADS after the first phase. Furthermore, pretreatment with the selective antagonist for the P2X1, P2X3 and P2X2+3 receptors, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP), significantly reduced the first phase, but not the second phase. The second phase was also not suppressed by intrathecal TNP-ATP after the first phase. 3. Capsaicin-induced nociceptive behaviour that has been shown to be a model for neurogenic pain, was also significantly suppressed by intrathecal pretreatment with PPADS or TNP-ATP. 4. Nociceptive behaviour in the first phase of the formalin test and in the capsaicin test were significantly inhibited by intrathecal pretreatment with alpha, beta-methylene ATP (alpha,betameATP: 5 microg mouse-1) 15 min prior to injection of formalin or capsaicin. This treatment has been previously shown to desensitize spinal P2X3 receptor subtypes in vivo. 5. These findings suggest that spinal endogenous ATP may play a role in (1) the formalin- and capsaicin-induced neurogenic pain via the PPADS- and TNP-ATP-sensitive P2X receptors which are also desensitized by alpha,betameATP (perhaps the P2X3 receptor subtype) and (2) formalin-induced inflammatory pain via PPADS-sensitive, TNP-ATP- and alpha,betameATP-insensitive P2X (and/or P2Y) receptors.
AuthorsM Tsuda, S Ueno, K Inoue
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 128 Issue 7 Pg. 1497-504 (Dec 1999) ISSN: 0007-1188 [Print] England
PMID10602329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Purinergic P2 Receptor Antagonists
  • Receptors, Purinergic P2
  • pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid
  • Formaldehyde
  • Pyridoxal Phosphate
  • 2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate
  • Adenosine Triphosphate
  • Capsaicin
Topics
  • Adenosine Triphosphate (analogs & derivatives, pharmacology, physiology)
  • Animals
  • Behavior, Animal (drug effects)
  • Capsaicin (pharmacology)
  • Formaldehyde (pharmacology)
  • Male
  • Mice
  • Motor Activity (drug effects)
  • Nociceptors (drug effects, physiology)
  • Pain (chemically induced, physiopathology)
  • Pain Measurement
  • Purinergic P2 Receptor Antagonists
  • Pyridoxal Phosphate (analogs & derivatives, pharmacology)
  • Receptors, Purinergic P2 (classification, physiology)
  • Spinal Cord (drug effects, physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: