Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opioids are commonly used for pain relief clinically and reduce hyperalgesia in most animal models. Two injections of acidic saline into one gastrocnemius muscle 5 days apart produce a long-lasting bilateral hyperalgesia without associated tissue damage. The current study was undertaken to assess the effects of opioid agonists on mechanical hyperalgesia induced by repeated intramuscular injections of acid. Morphine (mu-agonist), [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (mu-agonist; DAMGO), 4-[((alpha)R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (delta-agonist; SNC80), or (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride (kappa-agonist; U50,488) were administered intrathecally to activate opioid receptors once hyperalgesia was developed. Mechanical hyperalgesia was assessed by measuring the withdrawal thresholds to mechanical stimuli (von Frey filaments) before the first and second intramuscular injection, 24 h after the second intramuscular injection, and for 1 h after administration of the opioid agonist or vehicle. Morphine, DAMGO, and SNC80 dose dependently increased the mechanical withdrawal threshold back toward baseline responses. The reduction in hyperalgesia produced by morphine and DAMGO was prevented by H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) and that of SNC80 was prevented by naltrindole. U50,488 had no effect on the decreased mechanical withdrawal thresholds. Thus, activation of mu- and delta-, but not kappa-, opioid receptors in the spinal cord reduces mechanical hyperalgesia following repeated intramuscular injection of acid, thus validating the use of this new model of chronic muscle pain.
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PMID:Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists. 1218 74

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.
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PMID:Opioid modulation of ferret vagal afferent mechanosensitivity. 1825 89