Mu-Opioid Receptors in Ganglia, But Not in Muscle, Mediate Peripheral Analgesia in Rat Muscle Pain

BACKGROUND: Previous studies have demonstrated the participation of peripheral μ-opioid receptors (MOR) in the antinociceptive effect of systemically administered morphine and loperamide in an orofacial muscle pain model, induced by hypertonic saline, but not in a spinally innervated one, in rats. In this study, we determine whether this peripheral antinociceptive effect is due to the activation of MOR localized in the muscle, ganglia, or both. METHODS: To determine the local antinociceptive effect of morphine and loperamide, 2 models of acute muscle pain (trigeminal and spinal) were used. Also, to study the MOR expression, protein quantification was performed in the trigeminal and spinal ganglia, and in the muscles. RESULTS: The behavioral results show that the intramuscular injection of morphine and loperamide did not exert an antinociceptive effect in either muscle (morphine: P = .63, loperamide: P = .9). On the other hand, MOR expression was found in the ganglia but not in the muscles. This expression was on average 44% higher (95% CI, 33.3–53.9) in the trigeminal ganglia than in the spinal one. CONCLUSIONS: The peripheral antinociceptive effect of systemically administered opioids may be due to the activation of MOR in ganglia. The greater expression of MOR in trigeminal ganglia could explain the higher antinociceptive effect of opioids in orofacial muscle pain than in spinal muscle pain. Therefore, peripheral opioids could represent a promising approach for the treatment of orofacial pain. Accepted for publication October 23, 2017. Funding: This study was supported by the Ministry of Science and Innovation of Spain (SAF2012-40075-C02-01) and General Directorate for Scientific Research of Community of Madrid (S-2011/BMD-2308). The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Eva María Sánchez-Robles, PhD, Facultad Ciencias de la Salud, Área de Farmacología y Nutrición, Universidad Rey Juan Carlos, Avda Atenas, s/n. 28922 Alcorcón, Madrid, Spain. Address e-mail to eva.sanchez@urjc.es. © 2017 International Anesthesia Research Society

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