Lifestyle modifications in preclinical Rheumatoid Arthritis (RA) could delay the ongoing pathogenic immune processes and potentially prevent its onset. Physical exercise (PE) benefits RA patients; however, its impact in reducing the risk of developing RA has scarcely been studied. The objective was to describe the effects of low-intensity PE applied at the disease’s preclinical phase on the joints of DBA/1 mice with collagen-induced arthritis (CIA). Twelve mice with CIA were randomly distributed into two groups: the CIA-Ex group, which undertook treadmill PE, and the CIA-NoEx, which was not exercised. The effects of PE were evaluated through clinical, histological, transcriptomics, and immunodetection analyses in the mice’s hind paws. The CIA-Ex group showed lower joint inflammation and damage and a decreased expression of RA-related genes (Tnf Il2, Il10, Il12a, IL23a, and Tgfb1) and signaling pathways (Cytokines, Chemokines, JAK-STAT, MAPK, NF-kappa B, TNF, and TGF-beta). TNF-α expression was decreased by PE in the inflamed joints. Low-intensity PE in pre-arthritic CIA reduced the severity through joint down-expression of proinflammatory genes and proteins. Knowledge on the underlying mechanisms of PE in preclinical arthritis and its impact on reducing the risk of developing RA is still needed.

https://www.mdpi.com/2218-273X/13/3/488/pdf?version=1678156171

Low-Intensity Physical Exercise Decreases Inflammation and Joint Damage in the Preclinical Phase of a Rheumatoid Arthritis Murine Model

We aimed to compare the effects of three intensities of treadmill running on exercise-induced hypoalgesia (EIH) in healthy individuals. We anticipated that the primary and secondary changes in pain perception and modulation may differ between running intensities. Sixty-six women were randomly assigned to one of three treadmill running intensities for 35 min: 40% reserved heart rate (HRR), 55% HRR, or 70% HRR. The effects of EIH were assessed using pressure pain thresholds (PPT) and tolerance thresholds (PPTol). We measured conditional pain modulation (CPM). Compared with baseline, PPT and PPTol significantly increased in all groups during running and at the 5-10-min follow-up. The PPT and PPTol changes in the moderate- and low-intensity groups were significantly higher than those in the high-intensity group during running and 24 h after running, while the CPM responses of the high-intensity group were significantly reduced at the 24-h follow-up. Moderate- and low-intensity running may elicit significant primary and secondary (persisting over 24 h) EIH effects and increase CPM responses in females. However, high-intensity running induced only limited analgesic effects and reduced CPM responses, which may be attributed to the activation of endogenous pain modulation. 

Modulation of pain perceptions following treadmill running with different intensities in females

ABSTRACT Purpose To describe the observations of studies that have explored the effects of exercise on inflammation and tissue remodeling in animal models of inflammatory arthropathies including Rheumatoid Arthritis and Spondyloarthritis. Methods A search was performed at Pubmed, Scopus and Web of Science databases from 2010 to 2021. The selected articles were classified into those who reported positive and negative effects of exercise, and the characteristics of their experimental designs, including the animal model, the study groups, the exercise intervention and the evaluation techniques, were detailed. Results Thirteen original articles that met the selection criteria were included. The effects of exercise on the joint biology of mice with inflammatory arthritis were controversial. Although exercise benefits have been observed in some experimental designs, the majority of them have shown that exercise leads to exacerbation of inflammation, tissue remodeling, and processes associated with arthritis such as oxidative stress and hypoxia. Conclusion Further research is necessary as the existing guidelines do not consider the negative effects of the exercise evidenced in animal models. The potential risks of exercise for patients should be considered.

Exercise-driven exacerbation of inflammation: contribution of animal models of rheumatoid arthritis and spondyloarthritis

[Purpose] This study evaluated the effect of low-level laser therapy on inflammatory signs in an arthritis rat model as a foundation for elucidating the mechanism of the anti-inflammatory effect. [Materials and Methods] Eigteen Wistar rats were divided into three groups: group I (arthritis without low-level laser therapy), group II (arthritis with low-level laser therapy), and the control group (sham arthritis control). Arthritis was induced in the right knee by injecting a mixture of kaolin and carrageenan. Low-level laser therapy was continued for seven days after the onset of arthritis by 60 times of repeated irradiation for 10 seconds in the right knee joint area. The joint transverse diameter, pressure pain threshold in the affected knee joint, and mechanical paw withdrawal threshold at the distant site were evaluated the day before the injection and one, three, and seven days after the injection. Pathological changes were observed. [Results] Group II showed better improvement in swelling and pain in the affected knee joint and secondary hyperalgesia at the distance site when compared to group I. In group II, there was only mild infiltration of synovial cells, and the progression of arthritis was suppressed compared with that of group I. [Conclusion] Low-level laser therapy can mitigate swelling and inflammatory pain in the affected knee joint and prevent secondary hyperalgesia.

/pdf/effects-of-low-level-laser-therapy-on-inflammatory-symptoms-2d6crkgg.pdf

Effects of low-level laser therapy on inflammatory symptoms in an arthritis rat model

Objective: This study investigated the acute and follow-up exercise induced hypoalgesia (EIH) effects of treadmill running with various intensities and durations in healthy individuals, and evaluated the relation between the endogenous pain modulation and the EIH effects. Methods: A total of 66 healthy female individuals were enrolled in this study. Participants were randomly assigned into 3 intervention groups, and performed a running session at the intensity of 40% reserved heart rate (HRR), 55% HRR and 70% HRR for 35min. The EIH effects were evaluated by the changes of pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) before running, every 5min during running and 5min, 10min, 24h follow-ups. And the conditioned pain modulation (CPM) was also measured to determine the changes of endogenous pain modulation functions. Results: Compared with baseline, there was a significant increase of PPT and PPTol at arm and leg in all groups during running and 5-10min follow-ups. The PPT and PPTol changes of moderate and low intensity groups were significantly higher than the high intensity group during running and 24h after running. While the CPM responses of high intensity group were significantly reduced compared with other groups at 24h follow-up. Conclusion: Moderate and low intensity running may trigger the endogenous descending inhibition and elicit EIH effects following running and persisting over 24h. While the high intensity running only induced limited EIH effects for the activation of both descending pain inhibition and facilitation, with reduced CPM at 24h follow-up. And the improvement of PPTol might also contributed by the reward circuit in the pain cognitive processing, and might be limited by the fatigue induced via high intensity running.

Modulation of Pain Perception and Tolerance Following Treadmill Running with Different Intensities

This study investigated the effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats. Forty male Wistar rats (aged 8 weeks) divided into four groups randomly: arthritis (AR), immobilization after arthritis (Im), wheel-running exercise with the upper limbs following immobilization after arthritis induction (Im+Ex) and sham arthritis induction (Con). The knee joints of the Im and Im+Ex groups were immobilized with a cast for 4 weeks. In the Im+Ex group, wheel-running exercise was administered for 60 min/day (5 times/week). The swelling and the pressure pain threshold (PPT) of the knee joint were evaluated for observing the condition of inflammatory symptoms in affected area, and the paw withdraw response (PWR) was evaluated for observing the condition of secondary hyperalgesia in distant area. Especially, in order to evaluate histological inflammation in the knee joint, the number of macrophage (CD68-positive cells) in the synovium was examined. The expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn (L2-3 and L4-5) was examined to evaluate central sensitization. The Im+Ex group showed a significantly better recovery than the Im group in the swelling, PPTs, and PWRs. Additionally, CGRP expression of the spinal dorsal horn (L2-3 and L4-5) in the Im+Ex group was significantly decreased compared with the Im group. According to the results, upper limb exercise can decrease pain in the affected area, reduce hyperalgesia in distant areas, and suppress the central sensitization in the spinal dorsal horn by triggering exercise-induced hypoalgesia (EIH).

/pdf/the-effects-of-wheel-running-using-the-upper-limbs-following-3bcvny7oqi.pdf

The effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats.

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The effects of wheel-running using the upper limbs following immobilization after inducing arthritis in the knees of rats.