Absence of mechanical hyperalgesia after exercise (delayed onset muscle soreness) in neonatally capsaicin-treated rats

Kubo, Asako; Koyama, Michiyo; Tamura, Ryoko; Takagishi, Yoshiko; Murase, Shiori; Mizumura, Kazue

doi:10.1016/j.neures.2012.02.005

Cited by 19 publications

(13 citation statements)

References 26 publications

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“…Indeed, the mechanical response of C‐nociceptors has been demonstrated to be facilitated in a rat model of DOMS (Taguchi, Sato, & Mizumura, ). The development of mechanical hypersensitivity in this model was clearly suppressed by neonatal capsaicin treatment, further supporting the possible contribution of C‐fibres in DOMS (Kubo et al, ). Thick myelinated A‐fibres, including muscle spindle afferents, have also been suggested to be responsible for DOMS in human studies (Weerakkody, Whitehead, Canny, Gregory, & Proske, ).…”

Section: Introductionsupporting

confidence: 79%

Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise

Matsubara

Hayashi

Wakatsuki

et al. 2019

European Journal of Pain

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Background Delayed onset muscle soreness (DOMS) is characterized by mechanical hyperalgesia after lengthening contractions (LC). It is relatively common and causes disturbance for many people who require continuous exercise, yet its molecular and peripheral neural mechanisms are poorly understood. Methods We examined whether muscular myelinated Aδ‐fibres, in addition to unmyelinated C‐fibres, are involved in LC‐induced mechanical hypersensitivity, and whether acid‐sensing ion channel (ASIC)‐3 expressed in thin‐fibre afferents contributes to this type of pain using a rat model of DOMS. The peripheral contribution of ASIC3 was investigated using single‐fibre electrophysiological recordings in extensor digitorum longus muscle‐peroneal nerve preparations in vitro. Results Behavioural tests demonstrated a significant decrease of the muscular mechanical withdrawal threshold following LC to ankle extensor muscles, and it was improved by intramuscular injection of APETx2 (2.2 μM), a selective blocker of ASIC3. The lower concentration of APETx2 (0.22 µM) and its vehicle had no effect on the threshold. Intramuscular injection of APETx2 (2.2 μM) in naïve rats without LC did not affect the withdrawal threshold. In the ankle extensor muscles that underwent LC one day before the electrophysiological recordings, the mechanical response of Aδ‐ and C‐fibres was significantly facilitated (i.e. decreased response threshold and increased magnitude of the response). The facilitated mechanical response of the Aδ‐ and C‐fibres was significantly suppressed by selective blockade of ASIC3 with APETx2, but not by its vehicle. Conclusions These results clearly indicate that ASIC3 contributes to the augmented mechanical response of muscle thin‐fibre receptors in delayed onset muscular mechanical hypersensitivity after LC. Significance Here, we show that not only C‐ but also Aδ‐fibre nociceptors in the muscle are involved in mechanical hypersensitivity after lengthening contractions, and that acid‐sensing ion channel (ASIC)‐3 expressed in the thin‐fibre nociceptors is responsible for the mechanical hypersensitivity. ASIC3 might be a novel pharmacological target for pain after exercise.

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Section: Introductionsupporting

confidence: 79%

Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise

Matsubara

Hayashi

Wakatsuki

et al. 2019

European Journal of Pain

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“…In agreement, lengthening contractions failed to induce muscle mechanical hyperalgesia in rats with selective destruction of unmyelinated afferent C fibres by neonatal treatment with capsaicin, which demonstrated that the C fibres are essential in the transmission of the nociceptive information in DOMS (Kubo et al . ). The Aδ muscle afferent nociceptors were also linked to muscle mechanical hyperalgesia in a glial cell line‐derived neurotrophic factor‐dependent manner (Murase et al .…”

Section: Discussionmentioning

confidence: 97%

Interleukin‐10 limits intense acute swimming‐induced muscle mechanical hyperalgesia in mice

Borghi

Pinho‐Ribeiro

Zarpelon

et al. 2015

Experimental Physiology

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New Findings r What is the central question of this study?This study investigated the role of the endogenous anti-inflammatory cytokine interleukin-10 in intense acute swimming-induced muscle mechanical hyperalgesia in mice. r What is the main finding and its importance?Endogenous interleukin-10 has a key role in limiting exercise-induced muscle pain in a model presenting similarities to delayed-onset muscle soreness in mice. Interleukin-10 reduced muscle pain by diminishing leucocyte recruitment, hyperalgesic cytokine production, oxidative stress and myocyte damage. Interleukin-10 (IL-10) is an antihyperalgesic cytokine. In this study, IL-10-deficient (IL-10−/− ) mice were used to investigate the role of endogenous IL-10 in intense acute swimming-induced muscle mechanical hyperalgesia, which presents similarities with delayed-onset muscle soreness. An intense acute swimming session of 1 or 2 h induced significant muscle mechanical hyperalgesia in a time-dependent manner in wild-type mice compared with the sham group 24 h after the session, which was further increased in IL-10 −/− mice (P ˂ 0.05). Intraperitoneal treatment of wild-type mice with IL-10 (1-10 ng) reduced muscle mechanical hyperalgesia in a dose-dependent manner and reversed the enhanced muscle hyperalgesia in IL-10 −/− mice (P ˂ 0.05). The 2 h swimming session induced increases in tumour necrosis factor-α, interleukin-1β and IL-10 production in the soleus muscle. However, tumour necrosis factor-α and interleukin-1β production in the soleus muscle were even higher in IL-10 −/− mice between 2 and 6 h after the stimulus (P ˂ 0.05). There was no statistical difference in the levels of the antihyperalgesic cytokines interleukin-4, interleukin-5, interleukin-13 and transforming growth factor-β between wild-type and IL-10 −/− mice (P ˃ 0.05). Interleukin-10 deficiency also resulted in increased myeloperoxidase activity, greater depletion of reduced glutathione levels, increased superoxide anion production and the maintenance of high plasma concentrations of creatine kinase (until 24 h after the swimming session) in soleus muscle (P ˂ 0.05). These results demonstrate that endogenous IL-10 controls intense acute swimming-induced muscle mechanical hyperalgesia by limiting oxidative stress and cytokine production.

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“…The perception of muscle pain occurs because of sensitization and/or activation of group III (Aδ-fiber) and group IV (C-fiber) polymodal muscle afferents (nociceptors) in peripheral sites after overload and injuries in skeletal myocytes. Nociceptor neuron sensitization reduces its mechanical threshold to weak nonnociceptive stimuli or enhances neuronal activation to nociceptive stimuli leading to allodynia or hyperalgesia, respectively (Connolly et al, 2003;Graven-Nielsen and Arendt-Nielsen, 2003;Kubo et al, 2012;Matsubara et al, 2019). Signs of exercise-induced muscle pain become apparent between 24 and 48 h after the practice [delayed-onset muscle soreness (DOMS)] in response to unaccustomed exercise, especially those related to muscle fatigue, or of high intensity and long duration (MacIntyre et al, 1995;Taylor et al, 2000;Cheung et al, 2003;Graven-Nielsen and Arendt-Nielsen, 2003;Dannecker and Koltyn, 2014).…”

Section: Introductionmentioning

confidence: 99%

Intense Acute Swimming Induces Delayed-Onset Muscle Soreness Dependent on Spinal Cord Neuroinflammation

et al. 2022

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Unaccustomed exercise involving eccentric contractions, high intensity, or long duration are recognized to induce delayed-onset muscle soreness (DOMS). Myocyte damage and inflammation in affected peripheral tissues contribute to sensitize muscle nociceptors leading to muscle pain. However, despite the essential role of the spinal cord in the regulation of pain, spinal cord neuroinflammatory mechanisms in intense swimming-induced DOMS remain to be investigated. We hypothesized that spinal cord neuroinflammation contributes to DOMS. C57BL/6 mice swam for 2 h to induce DOMS, and nociceptive spinal cord mechanisms were evaluated. DOMS triggered the activation of astrocytes and microglia in the spinal cord 24 h after exercise compared to the sham group. DOMS and DOMS-induced spinal cord nuclear factor κB (NFκB) activation were reduced by intrathecal treatments with glial inhibitors (fluorocitrate, α-aminoadipate, and minocycline) and NFκB inhibitor [pyrrolidine dithiocarbamate (PDTC)]. Moreover, DOMS was also reduced by intrathecal treatments targeting C-X3-C motif chemokine ligand 1 (CX3CL1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β or with recombinant IL-10. In agreement, DOMS induced the mRNA and protein expressions of CX3CR1, TNF-α, IL-1β, IL-10, c-Fos, and oxidative stress in the spinal cord. All these immune and cellular alterations triggered by DOMS were amenable by intrathecal treatments with glial and NFκB inhibitors. These results support a role for spinal cord glial cells, via NFκB, cytokines/chemokines, and oxidative stress, in DOMS. Thus, unveiling neuroinflammatory mechanisms by which unaccustomed exercise induces central sensitization and consequently DOMS.

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Absence of mechanical hyperalgesia after exercise (delayed onset muscle soreness) in neonatally capsaicin-treated rats

Cited by 19 publications

References 26 publications

Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise

Thin‐fibre receptors expressing acid‐sensing ion channel 3 contribute to muscular mechanical hypersensitivity after exercise

Interleukin‐10 limits intense acute swimming‐induced muscle mechanical hyperalgesia in mice

Intense Acute Swimming Induces Delayed-Onset Muscle Soreness Dependent on Spinal Cord Neuroinflammation

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