Analgesic effects of cuminic alcohol (4-isopropylbenzyl alcohol), a monocyclic terpenoid, in animal models of nociceptive and neuropathic pain: Role of opioid receptors, L-arginine/NO/cGMP pathway, and inflammatory cytokines

Abstract

Cuminic alcohol (4-isopropylbenzyl alcohol; 4-IPBA) is a monocyclic terpenoid found in the analgesic medicinal plants Cuminum cyminum and Bunium persicum. The current study assessed the analgesic effects of 4-IPBA in different animal models of pain. Hot plate, formalin, and acetic acid tests were used to evaluate nociceptive pain in mice. The involvement of opioid receptors and the L-arginine/NO/cGMP/K+ channel pathway in 4-IPBA effects were investigated. Allodynia and hyperalgesia were assessed following peripheral neuropathy induced by chronic constriction of the sciatic nerve in rats. The spinal levels of inflammatory cytokines were measured using the ELISA method. The drugs and compounds were administered intraperitoneally. The results showed that 4-IPBA (200 and 400 mg/kg) significantly prolonged the hot plate latency. This effect was antagonized by naloxone (2 mg/kg). 4-IPBA (25–100 mg/kg) also significantly attenuated formalin- and acetic acid-induced nociceptive pain. L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg) reversed while L-NAME (30 mg/kg) and methylene blue (20 mg/kg) potentiated the antinociceptive effects of 4-IPBA in the writhing test. Glibenclamide (10 mg/kg) and tetraethylammonium chloride (4 mg/kg) did not have any influence on the 4-IPBA effect. Furthermore, 4-IPBA (6.25–25 mg/kg) significantly relieved mechanical allodynia, cold allodynia, and hyperalgesia in rats. The concentrations of TNF-α and IL-1β in the spinal cord of rats were decreased by 4-IPBA. No evidence of 4-IPBA-induced toxicity was found in behavioral or histopathological examinations. These results demonstrate that 4-IPBA attenuates nociceptive and neuropathic pain through the involvement of opioid receptors, the L-arginine/NO/cGMP pathway, and anti-inflammatory functions.