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Opioid modulation of ferret vagal afferent mechanosensitivity.
Am J Physiol Gastrointest Liver Physiol. 2008 Apr; 294(4):G963-70.AJ

Abstract

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 [d-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO), 2-(3, 4-dichlorophenyl)-N-methyl-N-[(1S)-1phenyl-2-(1-pyrrolidinyl) ethyl] acetamide hydrochlorine (ICI 199441), and (+)-4-[(alphaR)-alpha-((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 mu- and kappa-opioids have potent and selective peripheral effects on esophageal vagal afferents that may have applications in treatment of disorders of visceral sensation.

Authors+Show Affiliations

Nerve Gut Research Laboratory, Department of Gastroenterology and Hepatology, Level 1 Hanson Institute, Royal Adelaide Hospital, Frome Rd., Adelaide, SA 5000, Australia. amanda.page@health.sa.gov.auNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18258789

Citation

Page, Amanda J., et al. "Opioid Modulation of Ferret Vagal Afferent Mechanosensitivity." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 294, no. 4, 2008, pp. G963-70.
Page AJ, O'Donnell TA, Blackshaw LA. Opioid modulation of ferret vagal afferent mechanosensitivity. Am J Physiol Gastrointest Liver Physiol. 2008;294(4):G963-70.
Page, A. J., O'Donnell, T. A., & Blackshaw, L. A. (2008). Opioid modulation of ferret vagal afferent mechanosensitivity. American Journal of Physiology. Gastrointestinal and Liver Physiology, 294(4), G963-70. https://doi.org/10.1152/ajpgi.00562.2007
Page AJ, O'Donnell TA, Blackshaw LA. Opioid Modulation of Ferret Vagal Afferent Mechanosensitivity. Am J Physiol Gastrointest Liver Physiol. 2008;294(4):G963-70. PubMed PMID: 18258789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Opioid modulation of ferret vagal afferent mechanosensitivity. AU - Page,Amanda J, AU - O'Donnell,Tracey A, AU - Blackshaw,L Ashley, Y1 - 2008/02/07/ PY - 2008/2/9/pubmed PY - 2008/5/23/medline PY - 2008/2/9/entrez SP - G963 EP - 70 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 294 IS - 4 N2 - 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 [d-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (DAMGO), 2-(3, 4-dichlorophenyl)-N-methyl-N-[(1S)-1phenyl-2-(1-pyrrolidinyl) ethyl] acetamide hydrochlorine (ICI 199441), and (+)-4-[(alphaR)-alpha-((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 mu- and kappa-opioids have potent and selective peripheral effects on esophageal vagal afferents that may have applications in treatment of disorders of visceral sensation. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/18258789/Opioid_modulation_of_ferret_vagal_afferent_mechanosensitivity_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00562.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -