Analgesic Effects of Intranasal Ketamine in Rat Models of Facial Pain

Aims: To assess the analgesic effect of intranasal administration of S-ketamine in different rat models of facial pain. Methods: Nociceptive responses induced by formalin injected into the upper lip and facial hyperalgesia induced by capsaicin or carrageenan injected into the upper lip were used to evaluate the analgesic effect of intranasal ketamine in acute facial pain models in rats (n = 173). The effect of intranasal ketamine on heat and mechanical hyperalgesia induced by constriction of the infraorbital nerve (CION) was also evaluated. In addition, locomotor activity in the open field test was assessed after intranasal ketamine administration. Two-way repeated measures analysis of variance followed by Bonferroni post hoc correction were used to analyze all data. Results: Intranasal ketamine (0.5 mg/kg) failed to modify the first phase of the orofacial formalin test, but reduced the second phase by about 40%. Intranasal ketamine also reduced the facial heat hyperalgesia induced by capsaicin and carrageenan. In the CION model, intranasal ketamine at 0.5 mg/kg reversed the heat hyperalgesia and at 1 mg/kg attenuated the mechanical hyperalgesia 4 and 14 days after the surgery, respectively. The open field test did not reveal locomotor deficits in rats treated with intranasal ketamine. Conclusion: This study has demonstrated that intranasal ketamine produces analgesic effects in inflammatory and neuropathic facial pain models and may represent an adjuvant in the treatment of such conditions, especially when rapid pain relief is needed. Keywords: formalin test, heat hyperalgesia, inflammatory pain, ketamine, mechanical hyperalgesia, NMDA receptors, trigeminal neuropathic pain