TY - JOUR AB - Fibromyalgia (FM) is a chronic complex musculoskeletal disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep disturbance, memory defects and mood changes. Fisetin, a plant flavonoid polyphenol, has been reported to possess potent antioxidant, antinociceptive and neuroprotective activities. The present study aimed to evaluate the efficacy of fisetin against reserpine‑induced FM (RIF) in rats. RIF was induced in male Wistar rats (180‑220 gm) using reserpine (1 mg/kg; subcutaneous; once daily for 3 consecutive days) and the rats were treated with fisetin (5, 10 and 25 mg/kg) for 21 days. Various behavioral, biochemical and molecular parameters were evaluated. Administration of reserpine induced allodynia, hyperalgesia and depression, which were significantly ameliorated (P<0.05) by fisetin (10 and 25 mg/kg), as reflected by an increase in paw and tail withdrawal latency, increased paw withdrawal threshold, and decreased immobility time. Reserpine led to decreased biogenic amine levels [5‑hydroxytryptamine (5‑HT), noradrenaline (NA) and dopamine (DA)] and increased the ratio to their metabolite 3,4‑dihydroxyphenylacetic acid. 5‑hydroxyindoleacetic acid in the spinal cord, thalamus and prefrontal cortex was significantly decreased (P<0.05) by fisetin. Immunohistological analysis of brain tissue revealed that fisetin significantly inhibited (P<0.05) reserpine‑induced depletion of 5‑HT. It also significantly inhibited (P<0.05) elevated oxido‑nitrosative stress and reactive oxygen species (ROS) levels, as analyzed by flow cytometry in RIF rats. Fisetin exerts its antinociceptive and anti‑depressive potential via modulation of decreased levels of biogenic amines (5‑HT, NA and DA), elevated oxido‑nitrosative stress and ROS to ameliorate allodynia, hyperalgesia, and depression in experimental RIF. AD - Department of Neurological Rehabilitation, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450000, P.R. China Encephalopathy Department, The Traditional Chinese Medicine Hospital of Zhangqiu District, Jinan, Shandong 250200, P.R. China Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune‑411038, Maharashtra, India AU - Yao,Xianli AU - Li,Li AU - Kandhare,Amit ,D. AU - Mukherjee‑Kandhare,Anwesha ,A. AU - Bodhankar,Subhash ,L. DA - 2020/02/01 DO - 10.3892/etm.2019.8328 EP - 1355 IS - 2 JO - Exp Ther Med KW - 5‑HT dopamine FM fisetin immunohistochemistry NA ROS reserpine PY - 2020 SN - 1792-0981 1792-1015 SP - 1343 ST - Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol T2 - Experimental and Therapeutic Medicine TI - Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol UR - https://doi.org/10.3892/etm.2019.8328 VL - 19 ER -