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Screening the Role of Pronociceptive Molecules in a Rodent Model of Endometriosis Pain

  • Pedro Alvarez
    Affiliations
    Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, California

    Division of Neuroscience, University of California San Francisco, San Francisco, California
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  • Jon D. Levine
    Correspondence
    Address reprint requests to Jon D. Levine, MD, PhD, University of California, San Francisco, C-555, Box 0440, 521 Parnassus Ave, San Francisco, CA 94143-0440.
    Affiliations
    Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, California

    Division of Neuroscience, University of California San Francisco, San Francisco, California

    Department of Medicine, University of California San Francisco, San Francisco, California
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      Abstract

      Chronic pain is a major symptom in patients with endometriosis, a common gynecologic condition affecting women in their reproductive years. Although many proalgesic substances are produced by endometriosis lesions, experimental evidence supporting their relative roles is still lacking. Furthermore, it is unclear whether these proalgesic agents directly activate nociceptors to induce endometriosis pain. To determine their relative contribution to pain associated with endometriosis, we evaluated the intrathecal administration of oligodeoxynucleotides (ODNs) antisense to messenger RNA for receptors for 3 pronociceptive mediators known to be produced by the ectopic endometrium. Two weeks after the implant of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia was observed in operated rats. Intrathecal antisense ODN targeting messenger RNA for the interleukin 6 receptor–signaling complex subunit glycoprotein 130 and the nerve growth factor tyrosine kinase receptor A, but not their mismatch ODNs, reversibly attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal antisense ODN targeting the tumor necrosis factor receptor 1, at a dose that markedly inhibited intramuscularly injected tumor necrosis factor alpha, had only a small antihyperalgesic effect in this model. These results indicate the relative contribution of pronociceptive mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental approach presented here provides a novel method to evaluate for the differential contribution of mediators produced by other painful lesions as well as endometriosis lesions as targets for novel treatment of pain syndromes.

      Perspective

      This article presents evidence for the relative contribution of proalgesic mediators to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain. This approach can be used to identify potential targets for the treatment of endometriosis pain.

      Key words

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