Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states

Milad Sami Bitar, Katarina T. Bajic, Thameem Farook, Milini I. Thomas, Charles W.T. Pilcher

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Disorders of pain sensation including spontaneous pain, allodynia and hyperalgesia are commonly seen in neuropathic diabetic patients. A wealth of evidence indicates that spinal monoamine systems are implicated in pain modulation but whether abnormalities in these 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 (MHPG)/NE ratio was markedly suppressed in 30-day streptozotocin (STZ)-treated diabetic male and female rats. The density of [3H] p-aminoclonidine binding sites and the level of expression of mRNA encoding for α(2A)-adrenoceptor subtype were also reduced as a function of diabetes. In contrast, an increase in the density of [3H] prazosin binding to spinal synaptosomal membranes was evident in these animals. Clonidine-induced elevation in nociceptive threshold was attenuated in diabetics. Control animals subjected to chronic treatment with a supraphysiological dose of glucocorticoid (GC) exhibited a neurochemical pattern which is similar in many respects to that produced by the diabetic state. Both insulin and the GC receptor blocker, RU 486, restored most of the neurochemical and behavioural abnormalities of diabetes. Overall, the present study supports the concept that a diabetes-related deficit in spinal noradrenergic dynamics may be a reflection of an overactivity of the hypothalamic-pituitary-adrenal axis.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBrain Research
Volume830
Issue number1
DOIs
Publication statusPublished - 29 May 1999

Keywords

  • 3-Methoxy-4- hydroxyphenylglycol
  • Alpha adrenoceptor
  • Diabetes mellitus
  • Norepinephrine
  • Spinal cord

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