title: Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat.
abstract: While raised levels of monocyte chemoattractant protein 1 (MCP-1) have been observed in patients with chronic muscle pain, direct evidence for its role as an algogen in skeletal muscle is still lacking. In the rat, MCP-1 induces a dose-dependent mechanical hyperalgesia lasting for up to 6weeks. Following recovery, rats exhibited a markedly prolonged hyperalgesia to an intramuscular injection of prostaglandin E2, hyperalgesic priming. Intrathecal pretreatment with isolectin B4 (IB4)-saporin, which selectively destroys IB4-positive (IB4+) nociceptors, markedly decreased MCP-1-induced hyperalgesia and prevented the subsequent development of priming. To evaluate the involvement of MCP-1 in stress-induced chronic pain we administered, intrathecally, antisense (AS) or mismatch oligodeoxynucleotides directed against CCR2 (the canonical receptor for MCP-1) mRNA, during the exposure to water-avoidance stress, a model of stress-induced persistent muscle pain. The AS treatment attenuated this hyperalgesia, whereas IB4-saporin abolished water-avoidance stress-induced muscle hyperalgesia and prevented stress-induced hyperalgesic priming. These results indicate that MCP-1 induces persistent muscle hyperalgesia and a state of latent chronic sensitization to other algogens, by action on its cognate receptor on IB4+ nociceptors. Because MCP-1 also contributes to stress-induced widespread chronic muscle pain, it should be considered as a player in chronic musculoskeletal pain syndromes.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA Division of Neuroscience, University of California San Francisco, San Francisco, CA, USA Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alvarez
authors.forename: Paul G
authors.initials: PG
authors.lastname: Green
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000502:physiology* / Q000633:toxicity; D059350:Chronic Pain / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D063806:Myalgia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2
keywords: Fibromyalgia; Inflammation; Myalgia; Nociceptor; Stress