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1 Nerve Gut Research Laboratory, Royal Adelaide Hospital, Adelaide, South Australia, Australia
* To whom correspondence should be addressed. E-mail: amanda.page{at}health.sa.gov.au.
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 mu, kappa and delta opioids on mechanosensitive ferret esophageal vagal afferent endings investigated in vitro. The effects of selective agonists DAMGO, ICI 199441 and SNC 80 respectively on mechanosensory stimulus-response functions were quantified. DAMGO (10-7 - 10-5M) reduced the responses of tension receptors to circumferential tension (1-5g) by up to 50%, and the responses of mucosal receptors to mucosal stroking (10-1000mg von Frey hair) by >50%. DAMGO effects were reversed by naloxone (10-5M). Tension/mucosal (TM) receptor responses to tension and stroking were unaffected by DAMGO. ICI 199441 (10-6 - 10-5M) potently inhibited all responses except TM receptor responses to tension, and SNC 80 (10-5 - 10-3M) had no effect other than a minor inhibition of mucosal receptor responses to intense stimuli at 10-3M. We conclude that mu- and kappa- opioids have potent and selective peripheral effects on esophageal vagal afferents which may have applications in treatment of disorders of visceral sensation.
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