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Aim: To characterize the role of orexin‐1 receptors (OX1Rs) in ventrolateral periaqueductal grey matter (vlPAG) on modulation of capsaicin‐induced pulpal nociception in rats. Methodology: Sixty‐six adult male Wistar rats (2 months old) weighing between 230 and 260 g were used. The animals were cannulated for microinjection of drugs into the vlPAG matter. Pulpalgia was induced by intradental application of capsaicin solution (100 μg) into the incisor teeth of the rats. Ten min prior to capsaicin application, orexin‐A (50, 100 and 150 pmol L−1 per rat) was administered. Orexin‐A (150 pmol L−1) was also co‐administrated with SB‐334867 (40 nmol L−1 per rat), an OX1Rs antagonist; or bicuculline (1 μg per rat), a GABAA receptors antagonist. Moreover, treatment effects on the release of pro‐nociceptive modulator substance P (SP) in vlPAG and trigeminal nucleus caudalis (Vc) of rats were explored using an immunofluorescence technique. One‐way analysis of variance was used for the statistical analysis. Results: Orexin‐A dose‐dependently decreased capsaicin‐induced nociceptive behaviour. However, SB‐334867 (40 nmol L−1 per rat) pretreatment (P < 0.05), but not bicuculline (1 μg per rat), attenuated the analgesic effect of orexin‐A (150 pmol L−1). The level of SP was significantly increased in Vc and decreased in vlPAG of capsaicin‐treated rats (P < 0.05). Capsaicin‐induced changes in SP levels, however, were prohibited by orexin‐A treatment (150 pmol L−1) (P < 0.05). Conclusions: Orexin‐A administration into the vlPAG was associated with an inhibitory effect on capsaicin‐induced pulpal nociception and bidirectional effects on the induction of SP in vlPAG and Vc of rats. Central activation of OX1Rs is a potential therapeutic tool for pulpalgia. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of central administration of α‐pinene alone and in combination with either bicuculline or naloxone, as GABAA and μ‐opioid receptor antagonists, respectively, on capsaicin‐induced dental pulp stimulation in rats. Methodology: Forty‐eight adult male Wistar rats aged 2 months (230–270 g) were cannulated via their lateral ventricles for the central administration of the drugs. α‐Pinene was injected at 0.1, 0.2 and 0.4 μmol L−1. Then, dental pulp stimulation was induced by intradental application of capsaicin solution (100 μg), and nociceptive scores were recorded for up to 40 min. For investigation of the anti‐inflammatory effects of α‐pinene, expression of COX‐2 in the subnucleolus caudalis (Vc) of rats was determined using immunofluorescence staining. Nonparametric repeated measure Friedman and Kruskal–Wallis tests as well as parametric one‐way analysis of variance were used for the statistical analysis. Results: α‐Pinene at 0.2 and 0.4 μmol L−1 was able to decrease capsaicin‐induced nociception. Moreover, there was a significant increase in the expression of COX‐2‐positive cells in the Vc of capsaicin‐treated rats (P < 0.01). This effect was prohibited by α‐pinene (0.4 μmol L−1). Co‐administration of bicuculline (1 μg per rat) or naloxone (6 μg per rat) with α‐pinene (0.4 μmol L−1), however, prevented the inhibitory effects of α‐pinene on both capsaicin‐induced pulp nociception and COX‐2 over‐expression. Conclusions: Pinene exhibited significant curable effects on capsaicin‐induced pulpal nociception and inflammation mainly via pharmacological interfacing with GABAA and μ‐opioid receptors. [ABSTRACT FROM AUTHOR]