Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia

• Published in: Pain (Amsterdam) Vol. 146; no. 1; pp. 26 - 33
• Main Authors: Nagakura, Yukinori, Oe, Tomoya, Aoki, Toshiaki, Matsuoka, Nobuya
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.11.2009; Elsevier
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; Animal pain model; Animals; Biogenic amine; Biogenic Amines - metabolism; Biogenic Amines - physiology; Biological and medical sciences; Central Nervous System - metabolism; Depressive Disorder - chemically induced; Depressive Disorder - drug therapy; Depressive Disorder - psychology; Disease Models, Animal; Diseases of striated muscles. Neuromuscular diseases; Female; Fibromyalgia; Fibromyalgia - chemically induced; Fibromyalgia - drug therapy; Fibromyalgia - psychology; Fundamental and applied biological sciences. Psychology; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Illness and personality; Illness, stress and coping; Male; Medical sciences; Muscle pain; Muscle, Skeletal - physiology; Muscular Diseases - chemically induced; Muscular Diseases - drug therapy; Neurology; Pain - chemically induced; Pain - drug therapy; Pain Threshold - drug effects; Physical Stimulation; Pressure; Psychology and medicine; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Reserpine; Reserpine - pharmacology; Swimming - psychology; Tactile allodynia; Vesicular Monoamine Transport Proteins - antagonists & inhibitors; Fibromyalgia; Tactile allodynia; Animal pain model; Muscle pain; Reserpine; Biogenic amine; Animal model; Spinal cord; Rat; Diseases of the osteoarticular system; Central nervous system; Pregabalin; Encephalon; Pain; Thalamus; Face; Allodynia; Human; Rodentia; Catecholamine; Validity; Striated muscle disease; Vertebrata; Chronic; Mammalia; Dysfunction; Signal processing; Norepinephrine
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2009.05.024

Fibromyalgia is a prevalent and burdensome disorder characterized by chronic widespread pain and complex comorbid symptoms. To develop better treatments for pain-centered fibromyalgia symptoms, there is still a need for animal models which mimic the features of fibromyalgia patients. In the present study, we have established a fibromyalgia animal model by utilizing a never-before-published pharmacological effect of reserpine. Repeated administration of reserpine (1 mg/kg s.c., once daily, for three consecutive days) causes a significant decrease in the muscle pressure threshold and tactile allodynia, which are sustained for 1 week or more in both male and female rats. This treatment regimen decreases the amount of biogenic amines (dopamine, norepinephrine, and 5-hydroxytryptamine) in the spinal cord, thalamus, and prefrontal cortex, which are deeply involved in pain signal processing. It also significantly increases immobility time in the forced swim test, which is indicative of depression, a common comorbid symptom of fibromyalgia. Pregabalin, duloxetine, and pramipexole significantly attenuated the reserpine-induced decrease in muscle pressure threshold, but diclofenac did not. The validity of the use of this reserpinized animal as a fibromyalgia model is demonstrated from three different aspects, i.e., face validity (manifestation of chronic pain and comorbid symptoms), construct validity (dysfunction of biogenic amine-mediated central nervous system pain control is involved), and predictive validity (similar responses to treatments used in fibromyalgia patients). This animal model is expected to contribute to the better understanding of fibromyalgia pathophysiology and the evaluation of drugs, especially those which would activate biogenic amine system.