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- W2890829519 endingPage "32" @default.
- W2890829519 startingPage "21" @default.
- W2890829519 abstract "The mechanism of neuropathic pain is complex and unclear. Based on our results, we postulate that an intensification of the kynurenine pathway occurs as a consequence of nerve injury. The G protein-coupled receptor 35 (GPR35) is important for kynurenine pathway activation. Cyclic GMP-specific phosphodiesterase inhibitors have also been shown to have beneficial effects on neuropathic pain. Therefore, the aims of our research were to elucidate how a substance that acts as both an agonist of GPR35 and an inhibitor of phosphodiesterase influences neuropathic pain in a rat model. Here, we demonstrated that preemptive and repeated intrathecal (i.t.) administration (16 h and 1 h before injury and then after nerve ligation daily for 7 days) of zaprinast (1 μg/5 μl) significantly attenuated mechanical (von Frey test) and thermal (cold plate test) hypersensitivity measured on day 7 after chronic constriction injury, and the effect of even a single injection lasted up to 24 h. Our data indicate that zaprinast diminished the number of IBA1-positive cells and consequently attenuated the levels of IL-1beta, IL-6, IL-18, and NOS2 in the lumbar spinal cord and/or dorsal root ganglia. Our results also demonstrated that zaprinast potentiated the analgesic properties of morphine and buprenorphine. In summary, in a neuropathic pain model, zaprinast significantly reduced pain symptoms and enhanced the effectiveness of opioids. Our data provide new evidence that modulation of both GPR35 and phosphodiesterase could be an important strategy for innovative pharmacological treatments designed to decrease hypersensitivity evoked by nerve injury." @default.
- W2890829519 created "2018-09-27" @default.
- W2890829519 creator A5003101597 @default.
- W2890829519 creator A5012182352 @default.
- W2890829519 creator A5041585871 @default.
- W2890829519 creator A5068565210 @default.
- W2890829519 creator A5091216223 @default.
- W2890829519 date "2018-11-01" @default.
- W2890829519 modified "2023-10-03" @default.
- W2890829519 title "Zaprinast diminished pain and enhanced opioid analgesia in a rat neuropathic pain model" @default.
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