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NEUROREGULATION AND MOTILITY

Opioid modulation of ferret vagal afferent mechanosensitivity

¹Nerve Gut Research Laboratory, Department of Gastroenterology and Hepatology, Hanson Institute, Royal Adelaide Hospital; and ²Discipline of Medicine and ³Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, Australia

Submitted 3 December 2007 ; accepted in final form 2 February 2008

Despite universal use of opioids in the clinic to inhibit pain, there is relatively little known of their peripheral actions on sensory nerve endings, where in fact they may be better targeted with more widespread applications. Here we show differential effects of µ-, -, and -opioids on mechanosensitive ferret esophageal vagal afferent endings investigated in vitro. The effects of selective agonists [D-Ala²,N-Me-Phe⁴,Gly-ol⁵]-enkephalin (DAMGO), 2-(3, 4-dichlorophenyl)-N-methyl-N-[(1S)-1phenyl-2-(1-pyrrolidinyl) ethyl] acetamide hydrochlorine (ICI 199441), and (+)-4-[(R)--((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC-80), respectively, on mechanosensory stimulus-response functions were quantified. DAMGO (10^–7 to 10^–5 M) reduced the responses of tension receptors to circumferential tension (1–5 g) by up to 50%, and the responses of mucosal receptors to mucosal stroking (10–1,000 mg von Frey hair) by >50%. DAMGO effects were reversed by naloxone (10^–5 M). Tension/mucosal (TM) receptor responses to tension and stroking were unaffected by DAMGO. ICI 199441 (10^–6 to 10^–5 M) potently inhibited all responses except TM receptor responses to tension, and SNC-80 (10^–5 to 10^–3 M) had no effect other than a minor inhibition of mucosal receptor responses to intense stimuli at 10^–3 M. We conclude that µ- and -opioids have potent and selective peripheral effects on esophageal vagal afferents that may have applications in treatment of disorders of visceral sensation.

vagal afferents; neuromodulation; esophagus

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