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Naloxone Reversed Orofacial Analgesia Induced by Treadmill Exercise in a Rat Model of Parkinson's Disease: Exploring Opioid Receptors Involvement

Naloxone Reversed Orofacial Analgesia Induced by Treadmill Exercise in a Rat Model of Parkinson's Disease: Exploring Opioid Receptors Involvement

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Original abstract

Abstract Exercise-induced analgesia has been consistently associated with the activation of endogenous opioid pathways; however, the specific contribution of opioid receptor signaling to the reduction of orofacial pain in Parkinsonian conditions remains incompletely understood. Therefore, this study investigated whether pharmacological blockade of opioid receptors reverses the antinociceptive effect induced by exercise in a rat model of Parkinson’s disease (PD). Hemiparkinsonian rats were generated by unilateral 6-OHDA injection and subsequently submitted to a treadmill exercise protocol. To determine the involvement of endogenous opioids in exercise-induced analgesia, animals received the non-selective opioid receptor antagonist naloxone (1 mg/kg, i.p.), which exhibits high affinity for µ-opioid receptors, on day 28 after lesion induction, following six exercise sessions. Mechanical nociceptive thresholds in the orofacial region were assessed using the von Frey test at 15 and 30 minutes after naloxone administration. In addition, protein expression of µ- and δ-opioid receptors and the endogenous opioid peptide enkephalin was quantified in the trigeminal ganglion (TG) using Western blot analysis. We observed that the 6-OHDA + SED group showed a decrease in the mechanical threshold, which was reversed in the 6-OHDA + EX group. The antinociceptive effects of EX on orofacial pain were significantly reduced by naloxone, as showed in the behavioral test. Additionally, western blot analysis showed that the PD decreased the expression mu, delta and enkephalin in the TG and EX increased this expression. The current study shows that inhibiting opioid receptors, diminishes the facial antinociceptive effects of EX, indicating the involvement of opioid receptor in the analgesic effect of EX.

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