Exploring the Pain Attenuating Potential of Imatinib in Chronic Constriction Injury Model of Neuropathic Pain

Abstract

Background: Preclinical studies have identified three members of tyrosine kinase receptor family (Trk), TrkA, TrkB, and TrkC in dorsal root of ganglia (DRG), which carry sensory neural signals to the central nervous system from the peripheral nervous system in neuropathic pain. Imatinib is a selective tyrosine kinase inhibitor and widely employed as anti-cancer drug in myeloid leukemia and gastrointestinal stromal tumor. The present study was designed to investigate the potential of imatinib in neuropathic pain. Method: Neuropathic pain was induced by chronic constriction injury in rats by putting four loose ligatures around sciatic nerve. The extent of neuropathic pain was assessed by noting paw withdrawal threshold (mechanical hyperalgesia) in pin prick test, paw withdrawal latency in hot plate test (heat hyperalgesia) and paw withdrawal duration in acetone drop test (cold allodynia) before surgery and on 14th day post surgery. Result: There was a significant development of cold allodynia, mechanical and heat hyperalgesia on 14th day in CCI-subjected rats. Administration of imatinib (25 mg/kg and 50 mg/kg) significantly abolished the behavioural deficits (hyperalgesia and allodynia) induced by CCI in a dose-dependent manner. Conclusion: The observed beneficial effects of imatinib in reduction of behavioral deficits in CCI-subjected rats may be possibly attributed to tyrosine kinase inhibition in dorsal root ganglia neurons associated with the neuropathic pain.