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Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists.
J Pharmacol Exp Ther. 2002 Sep; 302(3):1146-50.JP

Abstract

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.

Authors+Show Affiliations

Physical Therapy and Rehabilitation Science Graduate Program, Neuroscience Graduate Program, Pain Research Program, University of Iowa, 2600 Steindler Building, Iowa City, IA 52242, USA. kathleen-sluka@uiowa.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12183674

Citation

Sluka, Kathleen A., et al. "Chronic Muscle Pain Induced By Repeated Acid Injection Is Reversed By Spinally Administered Mu- and Delta-, but Not Kappa-, Opioid Receptor Agonists." The Journal of Pharmacology and Experimental Therapeutics, vol. 302, no. 3, 2002, pp. 1146-50.
Sluka KA, Rohlwing JJ, Bussey RA, et al. Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists. J Pharmacol Exp Ther. 2002;302(3):1146-50.
Sluka, K. A., Rohlwing, J. J., Bussey, R. A., Eikenberry, S. A., & Wilken, J. M. (2002). Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists. The Journal of Pharmacology and Experimental Therapeutics, 302(3), 1146-50.
Sluka KA, et al. Chronic Muscle Pain Induced By Repeated Acid Injection Is Reversed By Spinally Administered Mu- and Delta-, but Not Kappa-, Opioid Receptor Agonists. J Pharmacol Exp Ther. 2002;302(3):1146-50. PubMed PMID: 12183674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists. AU - Sluka,Kathleen A, AU - Rohlwing,J J, AU - Bussey,R A, AU - Eikenberry,S A, AU - Wilken,J M, PY - 2002/8/17/pubmed PY - 2002/9/19/medline PY - 2002/8/17/entrez SP - 1146 EP - 50 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 302 IS - 3 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12183674/Chronic_muscle_pain_induced_by_repeated_acid_Injection_is_reversed_by_spinally_administered_mu__and_delta__but_not_kappa__opioid_receptor_agonists_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12183674 DB - PRIME DP - Unbound Medicine ER -