title: NSAIDs attenuate hyperalgesia induced by TRP channel activation.
abstract: Transient receptor potential (TRP) cation channels have been extensively investigated as targets for analgesic drug discovery. Because some non-steroidal anti-inflammatory drugs (NSAIDs) are structural analogs of prostaglandins (mediators of inflammation) and NSAIDs attenuate heat nociception and mechanical allodynia in models of inflammatory and neuropathic pain, we examined three widely used NSAIDs (diclofenac, ketorolac, and xefocam) on the activation of TRPA1 and TRPV1 channels using thermal paw withdrawal (Hargreaves) test and mechanical paw withdrawal (von Frey) test in male rats. Thermal withdrawal latencies and mechanical thresholds for both hind paws were obtained with 5, 15, 30, 45, 60, and 120 min intraplantar post-injection of TRPA1 agonizts, allyl isothiocyanate (AITC) (a natural compound of mustard oil) and cinnamaldehyde (CA), and TRPV1 agonist capsaicin or vehicle. Twenty minutes prior to the start of the experiment with TRP agonizts, diclofenac, ketorolac or xefocam were pre-injected in the same hindpaw and animals were examined by these two tests. After pretreatment of all three NSAIDs in the ipsilateral (injected) hindpaw that produced strong antinociceptive effects, AITC, CA, and capsaicin caused significant decreases in latency of the thermal withdrawal reflex compared with vehicle or the contralateral hindpaw. The same findings were observed for the paw withdrawal threshold. In approximately 30 min the effects of CA, AITC, and capsaicin returned to baseline. The data are different from our previous evidence, where TRPA1 agonizts AITC and CA and TRPV1 agonist capsaicin produced hyperalgesia for nearly 2 h and resulted in facilitation of these withdrawal reflexes (Tsagareli et al., 2010, 2013). Thus, our data showing that NSAIDs suppress thermal and mechanical hyperalgesia following TRP activation could presumably due to inactivation or desensitization of TRPA1 and TRPV1 channels by NSAIDs.
authors.affiliation: Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia.
authors.forename: Ivliane
authors.initials: I
authors.lastname: Nozadze
authors.affiliation: Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia.
authors.forename: Nana
authors.initials: N
authors.lastname: Tsiklauri
authors.affiliation: Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia.
authors.forename: Gulnaz
authors.initials: G
authors.lastname: Gurtskaia
authors.affiliation: Laboratory of Pain and Analgesia, Beritashvili Center for Experimental Biomedicine, Tbilisi, Georgia.
authors.forename: Merab G
authors.initials: MG
authors.lastname: Tsagareli
keywords: Allodynia; Cold pain; Heat pain; Hyperalgesia; Nociception; Signal transduction