Mechanical hyperalgesia correlates with insulin deficiency in normoglycemic streptozotocin-treated rats.
The triggers and pathogenesis of peripheral diabetic neuropathy are poorly understood, and this study evaluated the role of insulinopenia in nociceptive abnormalities in the streptozotocin (STZ) rat model of diabetes to test the hypothesis that, in addition to hyperglycemia, impairment of insulin signaling may be involved in progression of neuropathy. We measured blood glucose, plasma insulin, and sciatic nerve glucose and sorbitol levels, and withdrawal thresholds for hind limb pressure pain and heat pain in STZ-injected rats that developed hyperglycemia or remained normoglycemic. The pressure pain threshold did not change in vehicle-injected controls, but during the 2 weeks after STZ, it decreased by 25-40% in STZ-hyperglycemic and STZ-normoglycemic animals (P<0.05). Mean heat pain threshold did not change in STZ-normoglycemic rats, but increased by about 1.5 degrees C in STZ-hyperglycemic rats (P<0.05). These pain thresholds did not correlate with blood or nerve glucose or sorbitol levels, but both correlated with plasma insulin level in STZ-normoglycemic rats, and low-dose insulin replacement normalized the pressure threshold without affecting blood glucose level. Thus, at least one of early signs of diabetic neuropathy in STZ-treated rats, mechanical hyperalgesia, can be triggered by moderate insulinopenia, irrespective of glycemic status of the animals.
Romanovsky
Dmitry
D
Department of Anesthesiology, University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA.
Cruz
Nancy F
NF
Dienel
Gerald A
GA
Dobretsov
Maxim
M
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000172:deficiency* / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013012:Sorbitol / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D013012:Sorbitol; D005947:Glucose