Divergent Effect of Dezocine, Morphine and Sufentanil on Intestinal Motor Function in Rats

Xiaocui Bian, Renlong Zhou, Yuting Yang, Peiying Li, Yannan Hang, Youmin Hu, Liqun Yang, Daxiang Wen, Xiaocui Bian, Renlong Zhou, Yuting Yang, Peiying Li, Yannan Hang, Youmin Hu, Liqun Yang, Daxiang Wen

Abstract

Background: Opioid induced bowel dysfunction is the most common side effect of preoperatively administrated morphine, fentanyl and its derivative. However, the influence of dezocine on intestinal mobility is rarely reported. This study was designed to investigate the effects of dezocine, morphine and sufentanil on both intestinal smooth muscle contraction and propulsion in rats.

Methods: Contractile tension and frequency of isolated rat small intestine smooth muscle were measured using tension transducer after incubation with different concentrations of dezocine, morphine and sufentanil. The propulsive rate of methylene blue in rat intestinal tract was measured 30 minutes after intraperitoneal injection of morphine, sufentanil and dezocine. Percent of change in contractile tension and contraction frequency compared to baseline level were calculated to evaluate muscle contraction. Propulsive rate of methylene blue was calculated as the percentage of methylene blue moving distance in intestinal tract compared to the length of the small intestine.

Results: Morphine and sufentanil significantly increased the contractile tension of isolated small intestine smooth muscle at high doses. The contraction frequency did not change significantly among the 3 tested doses. Increasing the dose of dezocine from 1.7 mg.L(-1) to 10.2 mg.L(-1) did not change either the contractile tension or the contraction frequency. The propulsive rate of methylene blue in intestinal tract was significantly decreased after the treatment with morphine, sufentanil and dezocine (45.6%, 43.7%, and 42.1% respectively) compared to control group(57.1%), while the difference among the 3 drug groups were not significant.

Conclusion: Morphine and sufentanil may dose dependently increase the contractile tension and contraction ability of isolated rat small intestine smooth muscle, while dezocine has no significant effect on intestine smooth muscle contraction. However, all these opioids might impair small intestinal propulsion.

Keywords: contractile tension; dezocine; propulsive motility; small smooth muscle intestine.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Effect of morphine, sufentanil and dezocine on contractile tension and frequency of the isolated small intestine smooth muscle of rats. There was no difference in muscle contractile tension after 5mg.L-1 of morphine incubation compared to those of baseline, (P> 0.05), while there were significantly increased muscle tension at concentrations of the 10 and 30 mg.L-1group (P 0.05, figure 1C). Opioids whether morphine, sufentanil or dezocine, had no significant differences in the contractile frequency of the isolated small intestine smooth muscle of rats compared to basal values (P> 0.05). Values are means ± SEM; n=10 in each group; percent change in a given variable compared with its baseline; the baseline values and any opioids groups were compared by two-way analysis of variance (ANOVA) using the Bonferroni test. * p

Figure 2

Effect of morphine, sufentanil and…

Figure 2

Effect of morphine, sufentanil and dezocine on propulsive motility of small intestine of…

Figure 2
Effect of morphine, sufentanil and dezocine on propulsive motility of small intestine of rats. Animals were injected intraperitoneally with 1.04 mg.kg-1 of morphine, 2.08 μg.kg-1 of sufentanil and 1.04 mg.kg-1 of dezocine for treatment groups respectively and 1 ml saline as control. 30min after1ml methylene blue was given orally the rats were sacrificed and the bowels pulled into a straight line. Our result showed a significant decrease in propulsive distance rate in morphine, sufentanil and dezocine groups compared to those in control group (P 0.05). * p
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References
    1. Trescot AM, Glaser SE, Hansen H, Benyamin R, Patel S, Manchikanti L. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician. 2008;11:S181–200. - PubMed
    1. Ahlbeck K. Opioids: a two-faced Janus. Curr Med Res Opin. 2011;27:439–48. - PubMed
    1. Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs. 2003;63:649–71. - PubMed
    1. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182:11S–8S. - PubMed
    1. Holzer P. Treatment of opioid-induced gut dysfunction. Expert Opin Investig Drugs. 2007;16:181–94. - PubMed
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Figure 2
Figure 2
Effect of morphine, sufentanil and dezocine on propulsive motility of small intestine of rats. Animals were injected intraperitoneally with 1.04 mg.kg-1 of morphine, 2.08 μg.kg-1 of sufentanil and 1.04 mg.kg-1 of dezocine for treatment groups respectively and 1 ml saline as control. 30min after1ml methylene blue was given orally the rats were sacrificed and the bowels pulled into a straight line. Our result showed a significant decrease in propulsive distance rate in morphine, sufentanil and dezocine groups compared to those in control group (P 0.05). * p

References

    1. Trescot AM, Glaser SE, Hansen H, Benyamin R, Patel S, Manchikanti L. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician. 2008;11:S181–200.
    1. Ahlbeck K. Opioids: a two-faced Janus. Curr Med Res Opin. 2011;27:439–48.
    1. Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs. 2003;63:649–71.
    1. Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182:11S–8S.
    1. Holzer P. Treatment of opioid-induced gut dysfunction. Expert Opin Investig Drugs. 2007;16:181–94.
    1. Minkowitz HS, Singla NK, Evashenk MA, Hwang SS, Chiang YK, Hamel LG. et al. Pharmacokinetics of sublingual sufentanil tablets and efficacy and safety in the management of postoperative pain. Reg Anesth Pain Med. 2013;38:131–9.
    1. Brock C, Olesen SS, Olesen AE, Frokjaer JB, Andresen T, Drewes AM. Opioid-induced bowel dysfunction: pathophysiology and management. Drugs. 2012;72:1847–65.
    1. Liu YF, Chen KB, Lin HL, Ho CH, Liu SK, Liu YC. et al. Comparison of the effect of epidural and intravenous patient-controlled analgesia on bowel activity after cesarean section: a retrospective study of 726 Chinese patients. Acta Anaesthesiol Taiwan. 2009;47:22–7.
    1. Pandit UA, Kothary SP, Pandit SK. Intravenous dezocine for postoperative pain: a double-blind, placebo-controlled comparison with morphine. J Clin Pharmacol. 1986;26:275–80.
    1. Ouyang A. The partial opiate receptor agonists, dezocine and ciramadol act as mu receptor antagonists at the feline ileocecal sphincter. Life Sci. 1989;45:1491–7.
    1. Bueno L, Fioramonti J. Action of opiates on gastrointestinal function. Baillieres Clin Gastroenterol. 1988;2:123–39.
    1. Feng ZY, Mao LG, Lu Y. [Effect of morphine chloride on contractility of small intestinal muscle in vitro or in vivo and its mechanisms] Zhejiang Da Xue Xue Bao Yi Xue Ban. 2008;37:271–5.
    1. Junker U, Lux EA, Neugebauer EA, Basler HD. [Therapy of pain in multiborbid elderly patients] Med Monatsschr Pharm. 2009;32:175–81.
    1. McNicol ED, Boyce D, Schumann R, Carr DB. Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database Syst Rev; 2008. CD006332.
    1. Ross GR, Gabra BH, Dewey WL, Akbarali HI. Morphine tolerance in the mouse ileum and colon. J Pharmacol Exp Ther. 2008;327:561–72.
    1. Cohen RI, Edwards WT, Kezer EA, Ferrari DA, Liland AE, Smith ER. Serial intravenous doses of dezocine, morphine, and nalbuphine in the management of postoperative pain for outpatients. Anesth Analg. 1993;77:533–9.
    1. Poonyachoti S, Portoghese PS, Brown DR. Characterization of opioid receptors modulating neurogenic contractions of circular muscle from porcine ileum and evidence that delta- and kappa-opioid receptors are coexpressed in myenteric neurons. J Pharmacol Exp Ther. 2001;297:69–77.
    1. Chamouard P, Klein A, Martin E, Adloff M, Angel F. Regulatory role of enteric kappa opioid receptors in human colonic motility. Life Sci. 1993;53:1149–56.
    1. Brown DR, Poonyachoti S, Osinski MA, Kowalski TR, Pampusch MS, Elde RP. et al. Delta-opioid receptor mRNA expression and immunohistochemical localization in porcine ileum. Dig Dis Sci. 1998;43:1402–10.
    1. Manara L, Bianchetti A. The central and peripheral influences of opioids on gastrointestinal propulsion. Annu Rev Pharmacol Toxicol. 1985;25:249–73.
    1. Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett. 2004;361:192–5.
    1. Tavani A, Petrillo P, La Regina A, Sbacchi M. Role of peripheral mu, delta and kappa opioid receptors in opioid-induced inhibition of gastrointestinal transit in rats. J Pharmacol Exp Ther. 1990;254:91–7.
    1. Liu R, Huang XP, Yeliseev A, Xi J, Roth BL. Novel molecular targets of dezocine and their clinical implications. Anesthesiology. 2014;120:714–23.
    1. Menozzi A, Pozzoli C, Zullian C, Poli E, Serventi P, Bertini S. Inhibition of motility in isolated horse small intestine is mediated by kappa but not micro opioid receptors. Equine Vet J. 2012;44:368–70.
    1. Picker MJ. Discriminative stimulus effects of the mixed-opioid agonist/antagonist dezocine: cross-substitution by mu and delta opioid agonists. J Pharmacol Exp Ther. 1997;283:1009–17.

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