Further Validation of a Model of Fibromyalgia Syndrome in the Rat

  • Paul G. Green
    Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California
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  • Pedro Alvarez
    Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California
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  • Robert W. Gear
    Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California
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  • Dennis Mendoza
    Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California
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  • Jon D. Levine
    Address reprint requests to Dr. Jon D. Levine, MD, PhD, Departments of Medicine and Oral and Maxillofacial Surgery, University of California San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0440.
    Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California

    Department of Medicine, University of California San Francisco, San Francisco, California
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      We have recently developed an animal model of fibromyalgia syndrome in the rat. In this model, rats exposed to unpredictable sound stress develop a delayed onset enhancement and prolongation of cytokine-induced mechanical hyperalgesia in muscle and skin. In this study, we tested the hypothesis that our model also manifests symptoms of common comorbid diagnoses: irritable bowel syndrome, temporomandibular disorder, and anxiety. Both visceral sensitivity and cytokine hyperalgesia in masseter muscle were present in the stressed rats. Furthermore, in an established model of irritable bowel syndrome—water avoidance—we observed significant muscle hyperalgesia. Finally, using the elevated plus maze to assess for anxiety level, we observed a significantly higher anxiety level in sound stress-exposed rats. Thus, unpredictable sound stress produces a condition in the rat with several features—delayed onset visceral and temporomandibular hyperalgesia and increased anxiety, as well as cutaneous and muscle hyperalgesia—commonly found in patients with fibromyalgia syndrome.


      A stress model—unpredictable sound—in the rat exhibits several features (cutaneous, musculoskeletal, and visceral hyperalgesia, as well as anxiety) that are found in patients with fibromyalgia syndrome. Thus, this model may be used to test hypotheses about the underlying mechanisms and response to therapy in patients with fibromyalgia.

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