Background: Certain antineoplastic drugs cause gastrointestinal disorders even after the end of treatment. Enteric neuropathy has been associated with some of these alterations. Our goal was to assess the impact of repeated treatment with cisplatin and vincristine on the contractility of circular and longitudinal muscle strips isolated from the rat colon.Methods: Two cohorts of male rats were used: in cohort 1, rats received one intraperitoneal (ip) injection of saline or cisplatin (2 mg kg^–1 week^–1) on the first day of weeks 1–5; in cohort 2, rats received two cycles of five daily ip injections (Monday to Friday, weeks 1–2) of saline or vincristine (0.1 mg kg^–1 day^–1). Body weight and food and water intake were monitored throughout the study. One week after treatment, responses of colonic smooth muscle strips to acetylcholine (10^–9–10^–5 M) and electrical field stimulation (EFS, 0.1–20 Hz), before and after atropine (10^–6 M), were evaluated in an organ bath.Results: Both drugs decreased body weight gain. Compared to saline, cisplatin significantly decreased responses of both longitudinal and circular smooth muscle strips to EFS, whereas vincristine tended to increase them, although in a non-significant manner. No differences were observed in the muscle response to acetylcholine. Atropine abolished the contractile responses induced by acetylcholine, although those induced by EFS were only partially reduced in the presence of atropine.Conclusion: The findings suggest that although both drugs cause the development of enteric neuropathy, this seems to have a functional impact only in cisplatin-treated animals. Understanding the effects of chemotherapy on gastrointestinal motor function is vital for enhancing the quality of life of cancer patients.

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% confidence interval, 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.