Concurrent activation of the somatosensory forebrain and deactivation of periaqueductal gray associated with diabetes-induced neuropathic pain.
We combined behavioral testing with brain imaging using (99m)Tc-HMPAO (Amersham Health) to identify CNS structures reflecting alterations in pain perception in the streptozotocin (STZ) model of type I diabetes. We induced diabetic hyperglycemia (blood glucose >300 mg/dl) by injecting male Sprague-Dawley rats with STZ (45 mg/kg i.p.). Four weeks after STZ-diabetic rats exhibited behaviors indicative of neuropathic pain (hypersensitivity thermal stimuli) and this hypersensitivity persisted for up to 6 weeks. Imaging data in STZ-diabetic rats revealed significant increases in the activation of brain regions involved in pain processing after 6 weeks duration of diabetes. These regions included secondary somatosensory cortex, ventrobasal thalamic nuclei and the basolateral amygdala. In contrast, the activation in habenular nuclei and the midbrain periaqueductal gray were markedly decreased in STZ rats. These data suggest that pain in diabetic neuropathy may be due in part to hyperactivity in somatosensory structures coupled with a concurrent deactivation of structures mediating antinociception.
Paulson
Pamela E
PE
Neurology Research Laboratory, VA Medical Center, Ann Arbor, MI 48105, USA. plein@umich.edu
Wiley
John W
JW
Morrow
Thomas J
TJ
D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000503:physiopathology* / Q000523:psychology; D019262:Habenula / Q000503:physiopathology; D006943:Hyperglycemia / Q000209:etiology; D008297:Male; D009437:Neuralgia / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000503:physiopathology*; D016548:Prosencephalon / Q000503:physiopathology*; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013003:Somatosensory Cortex / Q000503:physiopathology; D019690:Technetium Tc 99m Exametazime; D013787:Thalamic Nuclei / Q000503:physiopathology
D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime