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Cited by 47Pain Mechanisms and TreatmentsPain Management and TreatmentMusculoskeletal pain and rehabilitation

Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat

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Alvarez, Pedro, Green, Paul G., Levine, Jon D.·2014·Pain
DOI 10.1016/j.pain.2014.03.004PMC PMC4303347
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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.

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  • CCL2 can bind to its receptor CCR2 on peripheral nerve terminals, thereby inducing nociplastic pain.

    “CCL2 can bind to its receptor CCR2 on peripheral nerve terminals, thereby inducing NPP (75).”

    From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [75]

    The Discussion (§5.3; page unavailable) says MCP-1/CCL2 acts through CCR2 on peripheral nociceptor terminals and induces long-lasting muscle hyperalgesia in rats. The paper does not establish that this response is nociplastic pain, so the claimed pain classification is unsupported. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Alvarez, P., Green, P. G., & Levine, J. D.
Affiliations
University of California, San Francisco (US)
Corresponding author
Levine, Jon D.
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-06
Volume
155
Issue
6
Pages
1161-1167
ISSN
0304-3959 (ISSN-L)
DOI
10.1016/j.pain.2014.03.004
PMC
PMC4303347
OpenAlex
W2045282997
Cited by
47
References
4
Citations by year
2026: 4 · 2025: 1 · 2024: 2 · 2023: 6 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 5
FWCI
2.89
Type
journal article
Language
en
Open access
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR063312)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
  • Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
Keywords
MCP-1, chronic muscle pain, mechanical hyperalgesia, hyperalgesic priming, CCR2, isolectin B4, nociceptors, antisense oligonucleotides, water avoidance stress, stress-induced pain, prostaglandin E2, musculoskeletal pain syndromes
MeSH terms
Animals, Hyperalgesia, Male, Rats, Sprague-Dawley, Chemokine CCL2, Rats, Chronic Pain, Myalgia

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