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

There exists a limited number of studies investigating the correlation between spinal adenosine A1 receptors and Vincristine-induced peripheral neuropathy (VIPN). This study explored the role of intrathecal N6-(2-phenylisopropyl)-adenosine R-(-)isomer (R-PIA) in neuropathic pain induced in rats by administering vincristine (100 μg/kg i.p.) for 10 days (two 5-day cycles with a 2-day pause).Pain was assessed by evaluating mechanical hyperalgesia, mechanical dynamic allodynia, heat hyperalgesia, and cold allodynia. Biochemically, tumor necrosis factor-alpha (TNF-α) level and myeloperoxidase (MPO) activity were measured in tissue from beneath the sciatic nerve.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). However, pretreatment with DPCPX (1,3-dipropyl-8-cyclopentylxanthine, 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.These results suggest that intrathecally administered R-PIA attenuates cold and mechanical static allodynia in a rat model of vincristine-induced peripheral neuropathy, partially due to its anti-inflammatory actions.