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.