Nerve injury-associated kinase: A sterile 20-like protein kinase up-regulated in dorsal root ganglia in a rat model of neuropathic pain

Partial injury of the rat sciatic nerve elicits a variety of characteristic chemical, electrophysical and anatomical changes in primary sensory neuron s and constitutes a physiologically relevant model of neuropathic pain. To elucidate molecular mechanisms that underlie the physiology of neuropathic pain, we have used messenger RNA differential display to identify genes tha t exhibit increased ipsilateral expression in L4/5 dorsal root ganglia, fol lowing unilateral partial ligation of the rat sciatic nerve. One set of par tial complementary DNA clones identified in this screen was found to encode a protein kinase, nerve injury-associated kinase. Cloning of the full-leng th human nerve injury-associated kinase complementary DNA, together with re combinant expression analysis, reveal nerve injury-associated kinase to be a functional member of a subgroup of sterile 20-like protein kinases charac terised by the presence of a putative carboxy terminal autoregulatory domai n. Induction of nerve injury-associated kinase expression in dorsal root ga nglia in the rat neuropathic pain model was confirmed by quantitative rever se transcription-polymerase chain reaction, and RNA in situ hybridization a nalysis revealed enhanced levels of nerve injury-associated kinase within n eurons. Together, our data implicate nerve injury-associated kinase as a novel upst ream component of an intracellular signalling cascade that is up-regulated in dorsal root ganglia neurons in response to sciatic nerve injury. (C) 200 0 IBRO. Published by Elsevier Science Ltd. All rights reserved.