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Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia.
Pain 2009; 146(1-2):26-33PAIN

Abstract

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 (1mg/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 1week 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.

Authors+Show Affiliations

Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yukinori.nagakura@jp.astellas.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19646816

Citation

Nagakura, Yukinori, et al. "Biogenic Amine Depletion Causes Chronic Muscular Pain and Tactile Allodynia Accompanied By Depression: a Putative Animal Model of Fibromyalgia." Pain, vol. 146, no. 1-2, 2009, pp. 26-33.
Nagakura Y, Oe T, Aoki T, et al. Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia. Pain. 2009;146(1-2):26-33.
Nagakura, Y., Oe, T., Aoki, T., & Matsuoka, N. (2009). Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia. Pain, 146(1-2), pp. 26-33. doi:10.1016/j.pain.2009.05.024.
Nagakura Y, et al. Biogenic Amine Depletion Causes Chronic Muscular Pain and Tactile Allodynia Accompanied By Depression: a Putative Animal Model of Fibromyalgia. Pain. 2009;146(1-2):26-33. PubMed PMID: 19646816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia. AU - Nagakura,Yukinori, AU - Oe,Tomoya, AU - Aoki,Toshiaki, AU - Matsuoka,Nobuya, Y1 - 2009/07/30/ PY - 2009/02/06/received PY - 2009/04/28/revised PY - 2009/05/27/accepted PY - 2009/8/4/entrez PY - 2009/8/4/pubmed PY - 2009/12/31/medline SP - 26 EP - 33 JF - Pain JO - Pain VL - 146 IS - 1-2 N2 - 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 (1mg/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 1week 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. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/19646816/Biogenic_amine_depletion_causes_chronic_muscular_pain_and_tactile_allodynia_accompanied_by_depression:_A_putative_animal_model_of_fibromyalgia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(09)00316-9 DB - PRIME DP - Unbound Medicine ER -