Antinociceptive activity of intraperitoneally administered novel and potent anticonvulsive compound, CY-PROLL-SS, in animal neuropathic pain models

Background: Neuropathic pain is still one of the most difficult pain states to be treated due to the lack of effective drugs. Although the mechanism of action of antiepileptic drugs in alleviating neuropathic pain is not fully understood, it is believed that the bases for both diseases are similar pathophysiologic disturbances. Therefore, in this article we explored the analgesic potential of a recently discovered compound CY-PROLL-SS (ADD 408003; 4-phenyl-perhydropyrrole[1,2-a]pyrazine-1,3-dione) with proved anticonvulsant activity. Methods: CY-PROLL-SS was delivered to animals systemically to assess the antinociceptive effects either in streptozocin (STZ)-induced diabetic or in chronic constriction injury (CCI) models of neuropathic pain after acute exposure to both thermal and mechanical stimulus. Results: Examined here compound dose-dependently reversed thermal and mechanical hyperalgesia induced by STZ single injection. Similar results were obtained for CCI-induced hyperalgesia; however, in this case an attenuation of thermal and reversal of mechanical hyperalgesia were observed. Conclusions: High doses of CY-PROLL-SS considerably alleviate peripheral neuropathic pain in model of STZ diabetic neuropathy and CCI. However, mechanisms remain to be elucidated. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.