Recent Advancements in Animal Models of Fibromyalgia

Nagakura, Yukinori

doi:10.1080/24708593.2016.1273986

Cited by 13 publications

(16 citation statements)

References 68 publications

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“…FM is a complex chronic musculoskeletal disorder characterized by chronic fatigue syndrome, neuropathic pain, allodynia, migraine, mood disorders, depression, sleep disturbances and neurocognitive impairment (13). RIF is highly reproducible and a well-established animal model that induces FM-like symptoms in murine experiments (22,36). Chronic administration of reserpine (1 mg/kg s.c., for 3 consecutive days) causes systemic depletion of biogenic amines (DA, 5-HT and NA), which results in increased nociception and depression in experimental rats (22).…”

Section: Discussionmentioning

confidence: 99%

“…RIF is highly reproducible and a well-established animal model that induces FM-like symptoms in murine experiments (22,36). Chronic administration of reserpine (1 mg/kg s.c., for 3 consecutive days) causes systemic depletion of biogenic amines (DA, 5-HT and NA), which results in increased nociception and depression in experimental rats (22). In the present study, treatment with fisetin significantly attenuated the reserpine-induced changes in the paw or tail withdrawal thresholds (as evaluated by the von Frey hair test, Randall-Selitto test and Hargreaves test), reserpine-induced depression (reflected by decreased immobility time in the FST and TST), reserpine-induced decreased levels of biogenic amines (5-HT, DA and NE) in the spinal cord, thalamus and prefrontal cortex, and elevated oxido-nitrosative stress and ROS in RIF rats.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a potent antioxidant, α-lipoic acid, has been proposed for the management of musculoskeletal pain associated with FM (21). A number of animal models that mimic FM have been employed for the development of new therapeutic moieties for the management of FM (22). Reserpine, a rauwolfia indole alkaloid, has been widely used as an antihypertensive agent, but its chronic administration is associated with major depression and musculoskeletal pain (22).…”

Section: Attenuation Of Reserpine-induced Fibromyalgia Via Ros and Sementioning

confidence: 99%

“…A number of animal models that mimic FM have been employed for the development of new therapeutic moieties for the management of FM (22). Reserpine, a rauwolfia indole alkaloid, has been widely used as an antihypertensive agent, but its chronic administration is associated with major depression and musculoskeletal pain (22). Thus, reserpine-induced FM (RIF) is a well-established and widely used animal model that mimics the etiological and clinical features of FM, including decreased levels of biogenic amines, depression-like syndrome and the induction of musculoskeletal pain reflected by an increased paw or tail withdrawal threshold (22).…”

Section: Attenuation Of Reserpine-induced Fibromyalgia Via Ros and Sementioning

confidence: 99%

“…RIF. FM was induced in rats according to a previously reported method (22,36). After the habituation process, reserpine (1 mg/kg, once daily) was administered by subcutaneous (s.c.) injection over the flank and repeated for 3 consecutive days, with varied sites of injection at the flank.…”

Section: Animalsmentioning

confidence: 99%

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Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Yao

Kandhare

et al. 2019

Exp Ther Med

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Attenuation Of Reserpine-induced Fibromyalgia Via Ros and Sementioning

confidence: 99%

Section: Attenuation Of Reserpine-induced Fibromyalgia Via Ros and Sementioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

See 3 more Smart Citations

Attenuation of reserpine‑induced fibromyalgia via ROS and serotonergic pathway modulation by fisetin, a plant flavonoid polyphenol

Yao

Kandhare

et al. 2019

Exp Ther Med

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Chronic generalized pain disrupts whole brain functional connectivity in mice

Nasseef

Singh

et al. 2021

Brain Imaging and Behavior

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Fibromyalgia (FM) is a generalized chronic pain condition whose pathophysiology is poorly understood, and both basic and translational research are needed to advance the field. Here we used the Sluka model to test whether FM-like pain in mice would produce detectable brain modifications using resting-state (rs) functional Magnetic Resonance Imaging (fMRI). Mice received intramuscular acid saline treatment, images were acquired at 7T 5 days post-treatment, and pain thresholds tested 3 weeks post-scanning. Data-driven Independent Component Analysis revealed significant reduction of functional connectivity (FC) across several component pairs, with major changes for the Retrosplenial cortex (RSP) central to the default mode network, and to a lesser extent the Periaqueductal gray (PAG), a key pain processing area. Seed-to-seed analysis focused on 14 pain-related areas showed strongest FC reduction for RSP with several cortical areas (somatosensory, prefrontal and insular), and for PAG with both cortical (somatosensory) and subcortical (habenula, thalamus, parabrachial nucleus) areas. RSP-PAG FC was also reduced, and this decreased FC tended to be positively correlated with pain levels at individual subject level. Finally, seed-voxelwise analysis focused on PAG confirmed seed-to-seed findings and, also detected reduced PAG FC with the anterior cingulate cortex, increasingly studied in aversive pain effects. In conclusion, FM-like pain triggers FC alterations in the mouse, which are detected by rs-fMRI and are reminiscent of some human findings. The study reveals the causal fingerprint

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