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Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy

대한마취과학회지 2020년 73권 5호 p.434 ~ 444
김경미, 정원영, 전인구, 박종연,
소속 상세정보
김경미 ( Kim Kyung-Mi ) - University of Ulsan College of Medicine Asan Medical Center Department of Anesthesiology and Pain Medicine
정원영 ( Jeong Won-Yeong ) - University of Ulsan College of Medicine Asan Medical Center Department of Anesthesiology and Pain Medicine
전인구 ( Jun In-Gu ) - University of Ulsan College of Medicine Asan Medical Center Department of Anesthesiology and Pain Medicine
박종연 ( Park Jong-Yeon ) - University of Ulsan College of Medicine Asan Medical Center Department of Anesthesiology and Pain Medicine

Abstract


Background: Studies investigating the correlation between spinal adenosine A1 receptors and vincristine-induced peripheral neuropathy (VIPN) are limited. This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in the rat model of VIPN.

Methods: Vincristine (100 μg/kg) was intraperitoneally administered for 10 days (two 5-day cycles with a 2-day pause) and VIPN was induced in rats. Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, thermal hyperalgesia, cold allodynia, and mechanical static allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in the tissue from beneath the sciatic nerve.

Results: Vincristine administration resulted in the development of cold allodynia, mechanical hyperalgesia, thermal hyperalgesia, mechanical dynamic allodynia, and mechanical static allodynia. Intrathecally administered R-PIA (1.0 and 3.0 μg/10 μl) reversed vincristine-induced neuropathic pain (cold and mechanical static allodynia). The attenuating effect peaked 15 min after intrathecal administration of R-PIA after which it decreased until 180 min. However, pretreatment with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 μg/10 μl) 15 min before intrathecal R-PIA administration significantly attenuated the antiallodynic effect of R-PIA. This antiallodynic effect of intrathecal R-PIA may be mediated through adenosine A1 receptors in the spinal cord. Intrathecally administered R-PIA also attenuated vincristine-induced increases in TNF-α level and MPO activity. However, pretreatment with intrathecal DPCPX significantly reversed this attenuation.

Conclusions: These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of VIPN, partially due to its anti-inflammatory actions.

키워드

Adenosine; DPCPX; Neuropathy; Receptor; R-PIA; Vincristine

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