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Role of transient receptor potential vanilloid‐1 (TRPV 1 ) and cannabinoid CB 1 receptors in paracetamol induced antinociception and hypothermia in mice
Author(s) -
Hamza May
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1125.11
Subject(s) - pharmacology , chemistry , trpv , cannabinoid receptor , am251 , nociception , hypothermia , cannabinoid , agonist , capsazepine , analgesic , antagonist , receptor , trpv1 , anesthesia , transient receptor potential channel , medicine , biochemistry
Paracetamol is one of the most popular and widely used analgesic antipyretics; however, its mode of action has not been clear. It was recently shown that paracetamol is metabolized in the brain and the spinal cord to form the potent TRPV 1 agonist N‐acylphenolamine (AM‐404). AM‐404 is also an inhibitor of the cellular uptake of the endogenous cannabinoid, anandamide. This study was designed to study the contribution of TRPV 1 and CB 1 receptors in the antinociceptive and hypothermic effects of paracetamol in mice. Capsazepine, a TRPV 1 antagonist, significantly reversed the antinociceptive effect of paracetamol in the formalin test, when administered i.p. at a dose of 10 mg/kg. A higher dose (30 mg/kg), however, failed to reverse the paracetamol induced antinociceptive effect. In contrast, the higher dose partially blocked paracetamol induced hypothermia but not the lower dose. Furthermore, AM‐251, a cannabinoid CB 1 receptor antagonist, when administered i.p. at a dose of 10 mg/kg, reversed the antinociceptive effect of paracetamol in the formalin test and blocked paracetamol induced hypothermia after 2 hours of paracetamol injection. In conclusion, both TRPV 1 and CB 1 receptors are involved in paracetamol induced antinociception in mice. Hypothermia, however, might involve other mediators and further studies are needed to investigate this point.