Fibromyalgia is a common, chronic, and generalized pain syndrome that is often associated with comorbid depression. The etiology of fibromyalgia is complex; most researchers have documented that the hallmark symptoms are due to the central nervous system’s abnormal functioning. Neurotransmitters such as serotonin, norepinephrine, and glutamate, have been reported to be key regulators of fibromyalgia syndrome. Daphnetin is a 7, 8 dihydroxy coumarin widely distributed in Thymelaeaceae family plants, possessing various activities such as anti-arthritic, anti-tumor, anti-malarial, and anti-parasitic. The present study was designed to explore the potential of daphnetin against reserpine-induced fibromyalgia in mice. In mice, a fibromyalgia-like state was achieved by injecting reserpine (0.5 mg/kg, s.c) continuously for 3 days. All behavioral tests were conducted on the 4th and 6th day of experimentation. Reserpine administration significantly increased the mechanical hypersensitivity in electronic von Frey (eVF) and pressure application measurement (PAM) tests. It also increased the immobility period and time to reach the platform in force swim test (FST) and Morris water maze (MWM) test, respectively. In the biochemical analysis, reserpine treatment upregulated the monoamine oxidase-A (MAO-A) activity and level of glutamate, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and thiobarbituric acid reactive substances (TBARS). Whereas, it decreased the level of glutathione (GSH), dopamine, serotonin, and norepinephrine. Daphnetin pretreatment attenuated the behavioral and biochemical changes induced by reserpine. Thus, the current investigation results delineate that daphnetin might exert its protective effect by inhibiting inflammatory stress and MAO-A-mediated neurotransmitter depletion and oxidative stress.
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Electronic von Frey
Pressure application measurement
Forced swim test
Morris water maze
Thiobarbituric acid reactive substances
Tumor necrosis factor-alpha
Central nervous system
Serotonin–norepinephrine reuptake inhibitors
Carboxy methyl cellulose
5-5′-Di-thio-bis [2-nitrobenzoic acid]
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The authors are grateful to the Department of Science and Technology, Government of India, for funding received under EMR (EMR/2016/005878). The authors gratefully acknowledge the financial support received from the University Grants Commission under RUSA 2.0 scheme.
Department of Science and Technology, Government of India (EMR/2016/005878), and University Grants Commission, RUSA 2.0 scheme.
Conflict of interest
The authors declare no conflicts of interest.
The whole investigation involving the use of mice was approved by the Institutional Animal Ethics Committee (Approval No. 226/CPCSEA/2018/23) and the experiments were performed according to ethical guidelines of the Ministry of Environment and Forests, Government of India.
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Communicated by Sreedharan Sajikumar.
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Singh, L., Kaur, A., Singh, A.P. et al. Daphnetin, a natural coumarin averts reserpine-induced fibromyalgia in mice: modulation of MAO-A. Exp Brain Res 239, 1451–1463 (2021). https://doi.org/10.1007/s00221-021-06064-1
- Oxidative stress