Antiallodynic and anti-inflammatory effects of intrathecal R-PIA in a rat model of vincristine-induced peripheral neuropathy
Autor: | Kim, Kyungmi, Jeong, Wonyeong, Jun, In Gu, Park, Jong Yeon |
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Rok vydání: | 2020 |
Předmět: |
Male
Vincristine Adenosine R-PIA DPCPX Anti-Inflammatory Agents Pharmacology lcsh:RD78.3-87.3 Rats Sprague-Dawley 03 medical and health sciences Adenosine A1 receptor 0302 clinical medicine Physical Stimulation medicine Experimental Research Article Animals Injections Spinal 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug biology business.industry medicine.disease Antineoplastic Agents Phytogenic Neuropathy Rats Cold Temperature Disease Models Animal Neuroprotective Agents Anesthesiology and Pain Medicine Peripheral neuropathy Allodynia lcsh:Anesthesiology Hyperalgesia Myeloperoxidase Neuropathic pain biology.protein Neuralgia Sciatic nerve medicine.symptom business 030217 neurology & neurosurgery Receptor medicine.drug |
Zdroj: | Korean Journal of Anesthesiology Korean Journal of Anesthesiology, Vol 73, Iss 5, Pp 434-444 (2020) |
ISSN: | 2005-7563 2005-6419 |
Popis: | 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. |
Databáze: | OpenAIRE |
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