Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states
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Elsevier Science B.V.
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Disorders of pain sensation including spontaneous pain, allodynia and hyperalgesia are commonly seen in neuropathic diabeticpatients. A wealth of evidence indicates that spinal monoamine systems are implicated in pain modulation but whether abnormalities inthese systems underlay such disorders is unclear. The present study was therefore initiated to investigate spinal noradrenergic dynamics . .during diabetes. Spinal release of norepinephrine NE represented by 3-methoxy-4-hydroxyphenylglycol MHPGrNE ratio was .w3xmarkedly suppressed in 30-day streptozotocin STZ -treated diabetic male and female rats. The density of Hp-aminoclonidine bindingsites and the level of expression of mRNA encoding fora-adrenoceptor subtype were also reduced as a function of diabetes. In2Aw3xcontrast, an increase in the density ofH prazosin binding to spinal synaptosomal membranes was evident in these animals.Clonidine-induced elevation in nociceptive threshold was attenuated in diabetics. Control animals subje...cted to chronic treatment with a .supraphysiological dose of glucocorticoid GC exhibited a neurochemical pattern which is similar in many respects to that produced bythe diabetic state. Both insulin and the GC receptor blocker, RU 486, restored most of the neurochemical and behavioural abnormalitiesof diabetes. Overall, the present study supports the concept that a diabetes-related deficit in spinal noradrenergic dynamics may be areflection of an overactivity of the hypothalamic–pituitary–adrenal axis.
Keywords:Diabetes mellitus / Spinal cord / Norepinephrine / 3-Methoxy-4-hydroxyphenylglycol / Alpha adrenoceptor
Source:Brain Research, 1999, 830, 1, 1-9
- Elsevier Science B.V.
- Kuwait University Grant MR 033