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. 2021 Mar 17;70(1):79-87.
doi: 10.33549/physiolres.934469. Epub 2021 Jan 14.

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

Y Tong  1 , K Ishikawa, R Sasaki, I Takeshita, J Sakamoto, M Okita
Affiliations

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

Y Tong et al. Physiol Res. .

Abstract

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).

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Conflict of interest statement

Conflict of Interest

There is no conflict of interest.

Figures

Fig. 1
Fig. 1
Changes in swelling and PPT of the knee joint in all groups. (a) Changes in swelling. (b) Changes of PPT. Data are mean ± SD. * significantly different from the Con group (p<0.05); + significantly different from the AR group (p<0.05); # significantly different from the Im group (p<0.05). PPT: pressure pain threshold.
Fig. 2
Fig. 2
Changes of the mechanical hyperalgesia of the hind paw in all groups. (a) 4 g von Frey filament (VFF) as a measurement of mechanical allodynia. (b) 15 g VFF as a measurement of mechanical hyperalgesia. Data are mean ± SD. * significantly different from the Con group (p<0.05); # significantly different from the Im group (p<0.05).
Fig. 3
Fig. 3
Numbers of CD68-positive cells in the synovium of the knee joint. (a) Representative photographs of macrophage immune-histochemistry in the synovium. (b) Comparison of the number of CD68-positive cells per unit area (1 mm2). Data are mean ± SD. * significantly different from the Con group (p<0.05).
Fig. 4
Fig. 4
CGRP expression in the spinal dorsal horn at the L2–3. (a) Representative photographs of CGRP immunohistochemistry in the spinal dorsal horn at the L2–3. (b) Percentage of fluorescence intensity of CGRP expression in the superficial layer (lamina I–II) and deep layers (lamina III–VI) at L2–3. Data are mean ± SD. * significantly different from the Con group (p<0.05); + significantly different from the AR group (p<0.05); # significantly different from the Im group (p<0.05). CGRP: calcitonin gene related peptide.
Fig. 5
Fig. 5
CGRP expression in the spinal dorsal horn at the L4–5. (a) Representative photographs of CGRP immunohistochemistry in the spinal dorsal horn at the L4–5. (b) Percentage of fluorescence intensity of CGRP expression in the superficial layer (lamina I–II) and deep layers (lamina III–VI) at L4–5. Data are means ± SD. * significantly different from the Con group (p<0.05); + significantly different from the AR group (p<0.05); # significantly different from the Im group (p<0.05). CGRP: calcitonin gene related peptide.
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