Afferent drive elicits ongoing pain in a model of advanced osteoarthritis

Alec Okun, Ping Liu, Peg Davis, Jiyang Ren, Bethany Remeniuk, Triza Brion, Michael H. Ossipov, Jennifer Xie, Gregory O. Dussor, Tamara King, Frank Porreca

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience pain at rest (ie, ongoing pain) that is generally resistant to nonsteroidal antiinflammatory drugs. Injection of monosodium iodoacetate (MIA) into the intraarticular space of the rodent knee is a well-established model of OA that elicits weight-bearing asymmetry and referred tactile and thermal hypersensitivity. Whether ongoing pain is present in this model is unknown. Additionally, the possible relationship of ongoing pain to MIA dose is not known. MIA produced weight asymmetry, joint osteolysis, and cartilage erosion across a range of doses (1, 3, and 4.8 mg). However, only rats treated with the highest dose of MIA showed conditioned place preference to a context paired with intraarticular lidocaine, indicating relief from ongoing pain. Diclofenac blocked the MIA-induced weight asymmetry but failed to block MIA-induced ongoing pain. Systemic AMG9810, a transient receptor potential V1 channel (TRPV1) antagonist, effectively blocked thermal hypersensitivity, but failed to block high-dose MIA-induced weight asymmetry or ongoing pain. Additionally, systemic or intraarticular HC030031, a TRPA1 antagonist, failed to block high-dose MIA-induced weight asymmetry or ongoing pain. Our studies suggest that a high dose of intraarticular MIA induces ongoing pain originating from the site of injury that is dependent on afferent fiber activity but apparently independent of TRPV1 or TRPA1 activation. Identification of mechanisms driving ongoing pain may enable development of improved treatments for patients with severe OA pain and diminish the need for joint replacement surgery.

Original languageEnglish (US)
Pages (from-to)924-933
Number of pages10
JournalPain
Volume153
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Anterior cingulate cortex
  • Axotomy
  • Negative reinforcement
  • Nerve injury
  • Spontaneous pain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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  • Cite this

    Okun, A., Liu, P., Davis, P., Ren, J., Remeniuk, B., Brion, T., Ossipov, M. H., Xie, J., Dussor, G. O., King, T., & Porreca, F. (2012). Afferent drive elicits ongoing pain in a model of advanced osteoarthritis. Pain, 153(4), 924-933. https://doi.org/10.1016/j.pain.2012.01.022