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

Abstract

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.

Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation

“…IL-10 deficiency enhances acute exercise-induced muscle hyperalgesia concomitantly with exacerbated oxidative stress [69]. On the other hand, increased nuclear levels of Nrf2 were accompanied by high levels of IL-10 in the plasma and the renal proximal tubules of treadmill-exercised rats [70].…”

Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

“…Fig 1 shows the time points of treatments and sample collection, which were based on previous studies or selected in experiments shown in the present study [1,2,21]. Mice received vehicle (Vh, 2% DMSO in saline, 200 μg/mL) or quercetin (Qc, 1–30 mg/kg, diluted in 2% DMSO in saline, 200 μg/mL) by intraperitoneal (i.p.)…”

“…Mice received vehicle (Vh, 2% DMSO in saline, 200 μg/mL) or quercetin (Qc, 1–30 mg/kg, diluted in 2% DMSO in saline, 200 μg/mL) by intraperitoneal (i.p.) route 30 min before swimming session plus reinforcements 12 h after, depending on the sample collection time point and were submitted to one session of intense acute swimming of 120 min [1,2,21]. The doses of 1, 3 and 10 mg/kg of quercetin were used only in the dose-response experiment presented in Fig 2.…”

“…After intense acute swimming session, the following tissues, parameters and time points were used for evaluation of: muscle mechanical hyperalgesia (6–48 h after swimming session); time spent in swimming behavior/immobility behavior during swimming session; plasmatic levels of glucose (2 and 24 h after swimming session); myeloperoxidase (MPO) and N-acetyl- β -D-glucosaminidase (NAG) activities in the soleus and gastrocnemius muscle (24 and 12 and 24 h after swimming session, respectively); cytokine (TNF-α, IL-1β and IL-10) production in the soleus and gastrocnemius muscle (immediately after swimming session); antioxidant capacity by 2,2´-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and reduced glutathione (GSH) levels as well as superoxide anion production (nitroblue tetrazolium [NBT] reduction) and lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) levels in the soleus and gastrocnemius muscles (2 h after swimming session); NFκB activation (24 h), and cyclooxygenase-2 (COX-2), gp91 phox , Nrf2, HO-1, and myoblast determination protein (MyoD) mRNA expression were determined in the soleus muscle (24 h after swimming session); creatine kinase (CK) levels in the blood (2 and 24 h after swimming session); cytokine (TNF-α, IL-1β and IL-10) production, GSH and TBARS levels in spinal cord (L4-L6; 2 h after swimming session); and glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) mRNA expression in the spinal cord (L4-L6; 24 h after swimming session). The experimental design and times described above were based on previous studies [1,2,21]. …”

“…The muscle mechanical hyperalgesia was evaluated 6–48 h after the swimming session. The swimming session period was defined in previous studies that demonstrated a swimming time-dependent muscle hyperalgesia [1,2,21]. Briefly, in the first study standardizing this model, we determined the swimming time necessary to induce significant muscle hyperalgesia using 30 min of swimming at five consecutive days or swimming only once for 30 min, 1h and 2 h of swimming.…”