8–10 Nerve injury essentially causes reorganization of the nervous system after peripheral afferent loss in peripheral nerve injury, triggering hypersensitive (central sensitization) pain memory. It has been reported that neuronal damage activates microglia and astrocytes in the dorsal horn of the spinal cord, causing pain through the production of inflammatory substances and abnormal nerve cell function. Neuropathic pain is caused by central or peripheral nerve damage. 5–7 Various reports have addressed therapeutic effects and mechanisms of treatment in humans and animals, but many unclear issues remain. Pharmacological treatment of neuropathic pain is limited, with 40‒60% of patients failing to achieve even partial relief of their pain. However, neuropathic pain is very difficult to treat effectively. Neuropathic pain patients have more difficulties in daily life and social life due to their pain.
Patients with neuropathic pain frequently present with abnormal sensation or hypersensitivity in the skin areas where peripheral nerves have been damaged. The clinical manifestations of neuropathic pain include pathological pain states, such as spontaneous pain, burning pain, and hyperalgesia. Its prevalence is considered to be constant or increasing, 2, 3 at a population prevalence of 6.9‒10%. Chronic pain is the most important cause of current and future morbidity-associated disability worldwide, with significant increases in both morbidity and disability loss each year. 1 An accurate classification of chronic neuropathic pain in the International Classification of Diseases (ICD)-11 is necessary to document the public health needs and therapeutic challenges associated with chronic neuropathic pain, which is a major contributor to the global burden of disease. However, almost 40 years thereafter, in 2020, pain was redefined as an unpleasant sensory and emotional experience related to or similar to actual or potential tissue damage. The International Association for the Study of Pain defined pain as “An unpleasant sensory and emotional experience with actual or potential tissue damage, or described in terms of such damage” in 1979. Keywords: CCR2, hippocampal dentate gyrus, microglia, neurogenesis, spinal dorsal horn, TRAF6 At 5 weeks post-CCI, both DCX and PROX1 expression was markedly increased in the Ex group compared to the No-Ex group.Ĭonclusion: Our findings suggest that regular exercise can improve the neuropathic pain-induced neurogenic dysfunction in the hippocampal dentate gyrus. In the hippocampus, DCX, but not PROX1, expression was significantly higher in the Ex group than in the No-Ex group at 3 weeks post-CCI. IBA1, GFAP, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 5 weeks post-CCI. In the spinal cord dorsal horn, IBA1, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 3 weeks post-CCI. Results: The 50% pain response threshold was significantly lower in the Ex than in the No-Ex group at 5 weeks post-CCI, indicating pain relief.
Using immunohistochemistry, we examined activation of glial cells (microglia and astrocytes) by CCR2 and TRAF6 expression in the spinal cord dorsal horn and DCX and PROX1 expression in the hippocampal dentate gyrus. The 50% pain response threshold was assessed by mechanical stimulation. The Ex group exercised on a treadmill at 20 m/min for 30 min, 5 days per week for 5 weeks post-CCI.
Normal rats (Normal group) were used as controls. Methods: CCI model rats were randomly divided into exercise (Ex) and no exercise (No-Ex) groups. This study created a chronic constriction injury (CCI) model in rats to examine the effects of regular exercise on neuropathic pain relief, elucidate the mechanism, and determine the effects of neuropathic pain in the hippocampus. Pharmacological treatments for neuropathic pain are limited, and 40– 60% of patients do not achieve even partial relief of their pain. Effective treatment of neuropathic pain is difficult. Purpose: Pain disrupts the daily and social lives of patients with neuropathic pain. Megumi Sumizono, 1, 2 Yushin Yoshizato, 1 Ryohei Yamamoto, 1 Takaki Imai, 1 Akira Tani, 2 Kazuki Nakanishi, 2 Tomomi Nakakogawa, 2 Teruki Matsuoka, 2 Ryoma Matsuzaki, 2 Takashi Tanaka, 3 Harutoshi Sakakima 2ġDepartment of Rehabilitation, Kyushu University of Nursing and Social Welfare, Kumamoto, Japan 2Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan 3Department of Rehabilitation, Kumamoto Health Science University, Kumamoto, JapanĬorrespondence: Megumi Sumizono, Department of Rehabilitation, Kyushu University of Nursing and Social Welfare, 888 Tominoo, Tamana, Kumamoto, 865-0062, Japan, Tel/Fax +81 968-75-1931, Email