METHODS: Formalin-induced paw licking model was used to assess the anti-nociceptive activity of CMEO and its major constituent, terpinolene (TP). The anti-nociceptive activity of these compounds was determined by investigating the roles of various non-opioid and NO-cGMP-K+ channels. Additionally, the anti-neuropathic potential of CMEO and TP was determined using cervical spinal cord contusion/CCS technique.

RESULTS: The CMEO exerted significant anti-nociceptive activity with a remarkable activity seen in the second phase of formalin-induced paw licking model and this activity were remarkably reversed by pre-treatment of naloxone (an opioid antagonist). Pretreatment with several types of NO-cGMP-potassium channel pathway meaningfully reversed the anti-nociceptive potential of CMEO in phase II of formalin model. Moreover, pre-treatment with several antagonists of non-opioid receptors revealed that only the antagonist of TRPV-1, serotonin type 3, 5-HT2, α2 adrenergic, and CB1 receptors (capsaicin, ondansetron, ketanserin, yohimbine, and SR141716A, respectively) reversed CMEO anti-nociception. CMEO and TP also remarkably reversed hyperalgesia and mechanical allodynia in the CCS technique.