Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states

Citation
Ms. Bitar et al., Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states, BRAIN RES, 830(1), 1999, pp. 1-9
Citations number
58
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
00068993 → ACNP
Volume
830
Issue
1
Year of publication
1999
Pages
1 - 9
Database
ISI
SICI code
0006-8993(19990529)830:1<1:SCNDID>2.0.ZU;2-Y
Abstract
Disorders of pain sensation including spontaneous pain, allodynia and hyper algesia are commonly seen in neuropathic diabetic patients. A wealth of evi dence indicates that spinal monoamine systems are implicated in pain modula tion but whether abnormalities in these systems underlay such disorders is unclear. The present study was therefore initiated to investigate spinal no radrenergic dynamics during diabetes. Spinal release of norepinephrine (NE) represented by 3-methoxy-4-hydroxyphenylglycol (MHPG)/NE ratio was markedl y suppressed in 30-day streptozotocin (STZ)-treated diabetic male and femal e rats. The density of [H-3] p-aminoclonidine binding sites and the level o f expression of mRNA encoding for alpha(2A)-adrenoceptor subtype were also reduced as a function of diabetes. In contrast, an increase in the density of [H-3] prazosin binding to spinal synaptosomal membranes was evident in t hese animals. Clonidine-induced elevation in nociceptive threshold was atte nuated in diabetics. Control animals subjected to chronic treatment with a supraphysiological dose of glucocorticoid (GC) exhibited a neurochemical pa ttern which is similar in many respects to that produced by the diabetic st ate. Both insulin and the GC receptor blocker, RU 486, restored most of the neurochemical and behavioural abnormalities of diabetes. Overall, the pres ent study supports the concept that a diabetes-related deficit in spinal no radrenergic dynamics may be a reflection of an overactivity of the hypothal amic-pituitary-adrenal axis. (C) 1999 Elsevier Science B.V. All rights rese rved.