Blockade of central cyclooxygenase (COX) pathways enhances the cannabinoid-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception

Abstract

The present study is the first to investigate the participation of central cyclooxygenase (COX) pathways in modulating the antinociceptive effects of intracisternally administered cannabinoid on nociception induced by inflammation of the temporomandibular joint (TMJ) in freely moving rats. Following intra-articular injection of 5% formalin in the TMJ, nociceptive scratching behavior was recorded for nine successive 5-min intervals in Sprague-Dawley rats. Intracisternal injection of 30 microg of WIN 55,212-2, a synthetic non-subtype-selective CB1/2 agonist, administered 20 min prior to formalin injection significantly reduced the number of scratches and duration of scratching induced by formalin compared with the vehicle-treated group. Antinociceptive effect of WIN 55,212-2 was blocked by intracisternal injection of 10 microg of AM251, a CB1 receptor-selective antagonist, but not by AM630, a CB2 receptor-selective antagonist. A 10 microg dose of WIN 55,212-2 that was ineffective in producing antinociception became effective following intracisternal administration of NS-398, a selective COX-2 inhibitor; indomethacin, a non-selective COX 1/2 inhibitor; acetaminophen, a putative COX-3 inhibitor, but not following pretreatment with the selective COX-1 inhibitor, SC-560. The ED(50) value of WIN 55,212-2 in the NS-398-treated group was significantly lower than that in the vehicle-treated group. Importantly, administration of low doses of COX inhibitors alone did not attenuate nociception. These results indicate that inhibition of central COX pathways, presumably via COX-2 inhibition, reduces inflammatory pain by enhancing the cannabinoid-induced antinociceptive effect. Based on our observations, combined administration of cannabinoids with COX inhibitors may hold a therapeutic promise in the treatment of inflammatory TMJ pain.

Effect of Combination of Preoperative Ibuprofen/Acetaminophen on the Success of the Inferior Alveolar Nerve Block in Patients with Symptomatic Irreversible Pulpitis

“…The analgesic activity of acetaminophen in rats can be completely prevented by addition of a cannabinoid (CB1) receptor antagonist (27,28). Blockade of central COX pathways can enhance a cannabinoidinduced antinociceptive effect (29).…”

Increased COX2 in the Trigeminal Nucleus Caudalis Is Involved in Orofacial Pain Induced by Experimental Tooth Movement

“…It was shown that spinal COX2 was activated and was involved in driving the initial hyperalgesia and allodynia following peripheral tissue injury (Ghilardi et al, 2004), and indomethacin (a nonselective COX inhibitor) could reduce spinal nociception during the formalin test (Yamamoto and Nozaki-Taguchi, 1996). Recent studies also found that central COX2 pathways participated in the IL-1b-induced hyperalgesia and cannabinoids modulated antinociception in the orofacial formalin test (Choi et al, 2003;Ahn et al, 2007). Furthermore, a recent study showed that conditional deletion of COX2 gene in central nervous system could inhibit the development of inflammatory mechanical allodynia (Vardeh et al, 2009).…”

“…Intrathecal administration of COX2 inhibitors was reported to decrease inflammation-induced PGE2 levels in the spinal cord of rats (Samad et al, 2001). Recently, it was found that central COX2 pathway played an important role in the IL-1b-induced hyperalgesia in the orofacial formalin test (Choi et al, 2003) and modulated the antinociceptive effects of cannabinoids in the formalin-induced temporomandibular joint nociception (Ahn et al, 2007). Furthermore, a recent study also showed that COX2 expressed within spinal dorsal horn neurons played an essential role in the development of inflammatory mechanical allodynia by increasing neuronal excitation (Vardeh et al, 2009).…”

Peri‐operative use of paracetamol

“…AM404 inhibits the cellular uptake of anandamide, an endocannabinoid, and is an agonist at the vanilloid receptor TRPV1, which is believed to play a central role in nociception. The analgesic activity of paracetamol in rats can be completely prevented by addition of a CB 1 receptor antagonist [34,35], while blockade of central COX pathways can enhance a cannabinoid-induced antinociceptive effect [36].…”