Spinal cord noradrenergic dynamics in diabetic and hypercortisolaemic states.
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 alpha2A-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.
Bitar
M S
MS
Department of Pharmacology, Faculty of Medicine, Kuwait University, PO Box 24923, Safat 13110, Kuwait. milad@hsc.kuniv.edu.kw
Bajic
K T
KT
Farook
T
T
Thomas
M I
MI
Pilcher
C W
CW
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000502:physiology*
D006727:Hormone Antagonists; D015735:Mifepristone; D008734:Methoxyhydroxyphenylglycol; D006854:Hydrocortisone; D009638:Norepinephrine