Nociceptive chemical hypersensitivity in the spinal cord of a rat reserpine-induced fibromyalgia model

Ejiri, Yuto; Uta, Daisuke; Ota, Hiroki; Mizumura, Kazue; Taguchi, Toru

doi:10.1016/j.neures.2022.03.005

Cited by 6 publications

(4 citation statements)

References 41 publications

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“…All these events may contribute to afferent hyperexcitability in the ASI model, with greater neurotransmitter release in the dorsal horn neurons that may contribute to a greater activation of these neurons, as well as to their central sensitization. Although these peripheral mechanisms can be clearly attributable to the ASI model, it is worth mentioning that it has been described also peripheral mechanisms in reserpine model 17 , 21 , 42 . Animals treated with repeated administrations of reserpine may show increased sensitivity of nociceptive afferent fibers to mechanical stimuli mediated by the increase in ASIC3 channels, and also to painful chemical stimuli (formalin).…”

Section: Discussionmentioning

confidence: 98%

“…Available RIM models manifest widespread pain and hyperalgesia without apparent tissue damage 15 , 16 , an increased proportion of activated microglial cells in the spinal dorsal horn 17 , and molecular changes (e.g., increased substance-P, TNF-alpha, lipid peroxide, and elevated expression of GluN2B-NMDA receptors) in supraspinal structures 18 , 19 . This model consists of repeated administration of reserpine to patterns of 3 (RIM3) 15 – 21 , 4 (RIM4) 16 and 6 (RIM6) 16 administrations, in which biogenic amine depletion may cause muscular pain and tactile allodynia accompanied by depressive-like behaviors. Intramuscular acid saline solution (ASI) injection is also an experimental model that induces hyperalgesia without apparent tissue damage 22 .…”

Section: Introductionmentioning

confidence: 99%

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Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5–6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Deulofeu

Homs

Vela³

et al. 2022

Sci Rep

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“…Similarly, animals treated with repeated administrations of reserpine showed increased sensitivity of nociceptive afferent fibers, mediated, at least in part, by ASIC3 channels. Peripheral hypersensitivity in RIM animals leads to overactivation and sensitization of dorsal horn neurons in the spinal cord, accompanied by decreased inhibitory inputs as well as the activation of spinal microglial cells [ 43 , 44 , 45 ]. Pregabalin is known to bind to the alpha-2-delta (α 2 δ 1 ) subunit of voltage-gated calcium channels, located at the terminals of the nociceptive afferents in the dorsal horn, causing presynaptic inhibition of calcium influx, and thus reduced calcium-induced release of excitatory neurotransmitters, including glutamate [ 46 ], thereby reducing the excitability of the spinal nociceptive neurons to relieve pain [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models

Bagó-Mas

Deulofeu

Vela³

et al. 2022

IJMS

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Sigma-1 receptor (s1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a s1R antagonist (BD1063) compared to pregabalin. ICR-CD1 female mice were subjected to either six repeated injections of reserpine, to cause reserpine-induced myalgia (RIM6), or acidified saline intramuscular injections (ASI). In these two models, we evaluated the effect of BD1063 and pregabalin on thermal hypersensitivity, anxiety-like and depression-like behaviors, and on spinal cord gliosis. BD1063 exerted an antinociceptive effect on both reflexive (thermal hyperalgesia) and nonreflexive (anxiety- and depression-like) pain behaviors, and reduced spinal astroglial and microglial reactivity, following repeated treatment for 2 weeks. Interestingly, the effects of BD1063 were long-term, lasting several weeks after treatment discontinuation in both fibromyalgia-like models. Similar results were obtained with pregabalin, but the effects on pain behaviors lasted for a shorter length of time, and pregabalin did not significantly modulate spinal glial reactivity. The inhibitory and long-lasting effect of pharmacological blockade of s1Rs on both sensory and affective dimensions of nociplastic-like pain and spinal cord gliosis in two experimental models of fibromyalgia support the application of this therapeutic strategy to treat fibromyalgia.

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“…Studies have shown that in a rat model of fibromyalgia, neurons in the spinal cord were hyperactivated, exhibiting higher background firing and increased mechanical responses, as well as increased excitatory synaptic input and decreased inhibitory synaptic input, resulting in nociceptive hypersensitivity reactions. 24 Acupuncture can down-regulate the phosphorylation levels of two subtypes of N-methyl-aspartate receptors (NMDARs), NR1 and NR2, and down-regulate the expression levels of transient receptor potential vanilloid 1 (TRPV1) and TRPV4 in the spinal cord to alleviate pain in mice with fibromyalgia. [25][26][27] In addition, acupuncture can exert analgesic effect by increasing the pain threshold and reducing pain sensitivity in patients with fibromyalgia.…”

mentioning

confidence: 99%

Knowledge Mapping of Acupuncture for Fibromyalgia from 1990 to 2022: A Bibliometric Analysis

Li¹,

Zheng²,

Chen³

et al. 2022

JPR

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Background Fibromyalgia is a rheumatic disease with no specific laboratory markers and is insensitive to hormonal drugs and nonsteroidal anti-inflammatory drugs commonly used to treat rheumatism. Guidelines recommend that non-pharmacological therapy should be the first-line treatment for fibromyalgia. Since the publication of the first diagnostic criteria for fibromyalgia in 1990, studies on acupuncture for fibromyalgia have been reported periodically. This study aims to explore the intellectual landscape of acupuncture for fibromyalgia since 1990, and to identify research trends and fronts in this field. Methods The Web of Science Core Collection Database was searched for publications on acupuncture for fibromyalgia from 1990 to 2022. VOSviewer and CiteSpace were used to analyze the annual publication, countries, institutions, authors and cited authors, journals and cited journals, references and keywords. Results A total of 280 publications were retrieved, and the number of publications showed an overall upward trend. The United States was the most productive country. China Medical University was the institution with the most publications. Lin Yi-wen was the most prolific author, while Wolfe was the most cited author. Evidence-Based Complementary and Alternative Medicine was the journal in which most of the research was published, while Pain was the most cited journal. An article by Wolfe (1990) had the most citations, but an article by Crofford (2001) had the highest centrality. The four most frequently used keywords in the included articles were mechanism, spinal cord, activation and sensitivity. Conclusion Acupuncture can effectively relieve pain in patients with fibromyalgia and improve accompanying symptoms such as anxiety and depression. However, the design of clinical trials still needs to be optimized to better verify the efficacy of acupuncture on various clinical symptoms of fibromyalgia. Exploring the central analgesic mechanism of acupuncture on fibromyalgia is also the focus research direction now and future.

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Nociceptive chemical hypersensitivity in the spinal cord of a rat reserpine-induced fibromyalgia model

Cited by 6 publications

References 41 publications

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models

Knowledge Mapping of Acupuncture for Fibromyalgia from 1990 to 2022: A Bibliometric Analysis

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