ATTENUATION OF IGF-1 ANTINOCICEPTIVE ACTION AND A REDUCTION IN SPINAL-CORD GENE-EXPRESSION OF ITS RECEPTOR IN EXPERIMENTAL DIABETES

Insulin-like growth factor I (IGF-1) is trophic to sensory, motor and sympathetic neurons. Intrathecal (i.t.) administration of IGF-1 produc ed analgesic effects when tail flick/withdrawal latency was used as an indicator. This action was blocked by genistein (an inhibitor of tyro sine kinase) but not by atipamezol (an alpha(2) adrenoreceptor antagon ist), naloxone (an opioid antagonist) or glibenclamide (a blocker of A TP sensitive K+ channels). Induction of diabetes with streptozotocin ( STZ, 55 mg/kg, i.v.) impaired the ability of IGF-1 to elevate nocicept ive threshold. This phenomenon was not seen in normal animals rendered hyperglycemic with D-glucose (20 mmol in 2.5 ml of saline, i.p.). PCR -based assay revealed that the lumbar region of the spinal cord expres ses mRNA transcripts for IGF-1 and its receptor. The rates of expressi on of both of these transcripts were reduced during diabetes. The abov e behavioral and biochemical abnormalities induced by the diabetic sta te were partially restored following replacement therapy with insulin. Overall, our data suggest that a receptor-linked tyrosine kinase medi ates the antinociceptive effect of IGF-1. Additionally, the attenuatio n in the ability of IGF-1 to elevate nociceptive threshold may be a co nsequence of reduced gene expression of IGF-1 receptor within the spin al cord. (C) 1998 International Association for the Study of Pain. Pub lished by Elsevier Science B.V.