3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury

Abstract

Purpose: There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs’ influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed.

Methods: Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed.

Results: Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED₅₀ values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5–100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content.

Conclusions: LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.

• Chronic constriction injury of the sciatic nerve
• dihydrofuran-2-one
• mice
• nerve growth factor
• pregabalin

Declaration of interest

This study was financially supported by the Jagiellonian University grant K/ZDS/003329. The authors declare that they have no conflict of interest. The authors alone are responsible for the content and writing of the paper.