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 (μ-agonist), [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (μ-agonist; DAMGO), 4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (δ-agonist; SNC80), or (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride (κ-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 byH-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(CTAP) and that of SNC80 was prevented by naltrindole. U50,488 had no effect on the decreased mechanical withdrawal thresholds. Thus, activation of μ- and δ-, but not κ-, 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.
Footnotes
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This study was supported by National Institutes of Health Grants R01 NS 39734 and K02 AR 02201.
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DOI: 10.1124/jpet.102.033167
- Abbreviations:
- NMDA
- N-methyl-d-aspartate
- DAMGO
- [d-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin
- DMSO
- dimethyl sulfoxide
- SNC80
- 4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide
- U50,488
- (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride
- CTAP
- H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2
- %MPE
- percentage of maximal possible effect
- Received January 15, 2002.
- Accepted May 10, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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