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).

Department of Physical Therapy Science Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan

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CHUGANJI S, NAKANO J, SEKINO Y, HAMAUE Y, SAKAMOTO J, OKITA M. Hyperalgesia in an immobilized rat hindlimb: effect of treadmill exercise using non-immobilized limbs. Neurosci Lett. 2015;584:66–70. doi: 10.1016/j.neulet.2014.09.054. PubMed DOI

DIETRICH A, McDANIEL WF. Endocannabinoids and exercise. Br J Sports Med. 2004;38:536–541. doi: 10.1136/bjsm.2004.011718. PubMed DOI PMC

ISHIKAWA K, KAJIWARA Y, SAKAMOTO J, SASAKI R, GOTO K, HONDA Y, KATAOKA H, OKITA M. Low-intensity muscle contraction exercise following the onset of arthritis improves hyperalgesia via reduction of joint inflammation and central sensitization in the spinal cord in a rat model. Neurosci Lett. 2019;706:18–23. doi: 10.1016/j.neulet.2019.04.031. PubMed DOI

KAMI K, TAJIMA F, SENBA E. Exercise-induced hypoalgesia: potential mechanisms in animal models of neuropathic pain. Anat Sci Int. 2017;92:79–90. doi: 10.1007/s12565-016-0360-z. PubMed DOI

KAMI K, TAGUCHI S, TAJIMA F, SENBA E. Mechanisms and effects of forced and voluntary exercises on exercise-induced hypoalgesia in neuropathic pain model mice. Pain Res. 2015;30:216–229. doi: 10.11154/pain.30.216. DOI

KAWAI S, TAKAGI Y, KANEKO S, KUROSAWA T. Effect of three types of mixed anesthetic agents alternate to ketamine in mice. Exp Anim. 2011;60:481–487. doi: 10.1538/expanim.60.481. PubMed DOI

KOLTYN KF, BRELLENTHIN AG, COOK DB, SEHGAL N, HILLARD C. Mechanisms of exercise-induced hypoalgesia. J Pain. 2014;15:1294–1304. doi: 10.1016/j.jpain.2014.09.006. PubMed DOI PMC

MOLANDER C, XU Q, RIVERO-MELIAN C, GRANT G. Cytoarchitectonic organization of the spinal cord in the rat: II. The cervical and upper thoracic cord. J Comp Neurol. 1989;289:375–385. doi: 10.1002/cne.902890303. PubMed DOI

NAKABAYASHI K, SAKAMOTO J, KATAOKA H, KONDO Y, HAMAUE Y, HONDA Y, NAKANO J, OKITA M. Effect of continuous passive motion initiated after the onset of arthritis on inflammation and secondary hyperalgesia in rats. Physiol Res. 2016;65:683–691. doi: 10.33549/physiolres.933214. PubMed DOI

NAKANO J, SEKINO Y, HAMAUE Y, SAKAMOTO J, YOSHIMURA T, ORIGUCHI T, OKITA M. Changes in hind paw epidermal thickness, peripheral nerve distribution and mechanical sensitivity after immobilization in rats. Physiol Res. 2012;61:643–647. doi: 10.33549/physiolres.932362. PubMed DOI

NAUGLE KM, FILLINGIM RB, RILEY JL. A meta-analytic review of the hypoalgesic effects of exercise. J Pain. 2012;13:1139–1150. doi: 10.1016/j.jpain.2012.09.006. PubMed DOI PMC

NEUGEBAUER V, HAN JS, ADWANIKAR H, FU Y, JI G. Techniques for assessing knee joint pain in arthritis. Mol Pain. 2007;3:8. doi: 10.1186/1744-8069-3-8. PubMed DOI PMC

O’CONNOR SR, TULLY MA, RYAN B, BLEAKLEY CM, BAXTER GD, BRADLEY JM, McDONOUGH SM. Walking exercise for chronic musculoskeletal pain: systematic review and meta-analysis. Arch Phys Med Rehabil. 2015;96:724–734.e3. doi: 10.1016/j.apmr.2014.12.003. PubMed DOI

PELESHOK JC, RIBEIRO-DA-SILVA A. Delayed reinnervation by nonpeptidergic nociceptive afferents of the glabrous skin of the rat hindpaw in a neuropathic pain model. J Comp Neurol. 2011;519:49–63. doi: 10.1002/cne.22500. PubMed DOI

RADHAKRISHNAN R, MOORE SA, SLUKA KA. Unilateral carrageenan injection into muscle or joint induces chronic bilateral hyperalgesia in rats. Pain. 2003;104:567–577. doi: 10.1016/s0304-3959(03)00114-3. PubMed DOI PMC

STAGG NJ, MATA HP, IBRAHIM MM, HENRIKSEN EJ, PORRECA F, VANDERAH TW, MALAN TP., JR Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology. 2011;114:940–948. doi: 10.1097/aln.0b013e318210f880. PubMed DOI PMC

TAJERIAN M, CLARK JD. Nonpharmacological interventions in targeting pain-related brain plasticity. Neural Plast. 2017;2017:2038573. doi: 10.1155/2017/2038573. PubMed DOI PMC

VAEGTER HB, HANDBERG G, GRAVEN-NIELSEN T. Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans. Pain. 2014;155:158–167. doi: 10.1016/j.pain.2013.09.023. PubMed DOI