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 produced analgesic effects when tail flick/withdrawal latency was used as an indicator. This action was blocked by genistein (an inhibitor of tyrosine kinase) but not by atipamezol (an alpha2 adrenoreceptor antagonist), naloxone (an opioid antagonist) or glibenclamide (a blocker of ATP sensitive K+ channels). Induction of diabetes with streptozotocin (STZ, 55 mg/kg, i.v.) impaired the ability of IGF-1 to elevate nociceptive 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 expresses mRNA transcripts for IGF-1 and its receptor. The rates of expression of both of these transcripts were reduced during diabetes. The above behavioral and biochemical abnormalities induced by the diabetic state were partially restored following replacement therapy with insulin. Overall, our data suggest that a receptor-linked tyrosine kinase mediates the antinociceptive effect of IGF-1. Additionally, the attenuation in the ability of IGF-1 to elevate nociceptive threshold may be a consequence of reduced gene expression of IGF-1 receptor within the spinal cord.
Bitar
Milad S
MS
Department of Pharmacology, Faculty of Medicine, Kuwait University, Post Box 24923, 13110 Safat, Kuwait.
Pilcher
T C W
TCW
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D007278:Injections, Spinal; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism*
D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I