Patterns of increased brain activity indicative of pain in a rat model of peripheral mononeuropathy.
Regional changes in brain neural activity were examined in rats with painful peripheral mononeuropathy (chronic constrictive injury, CCI) by using the fully quantitative 14C-2-deoxyglucose (2-DG) autoradiographic technique to measure local glucose utilization rate. CCI rats used in the experiment exhibited demonstrable thermal hyperalgesia and spontaneous pain behaviors 10 d after sciatic nerve ligation when the 2-DG experiment was carried out. In the absence of overt peripheral stimulation, reliable increases in 2-DG metabolic activity were observed in CCI rats as compared to sham-operated rats within extensive brain regions that have been implicated in supraspinal nociceptive processing. These brain regions included cortical somatosensory areas, cingulate cortex, amygdala, ventral posterolateral thalamic nucleus, posterior thalamic nucleus, hypothalamic arcuate nucleus, central gray matter, deep layers of superior colliculus, pontine reticular nuclei, locus coeruleus, parabrachial nucleus, gigantocellular reticular nucleus, and paragigantocellular nucleus. The increase in 2-DG metabolic activity was bilateral in most brain regions of CCI rats. However, somatosensory regions within the thalamus and the cerebral cortex were activated in CCI rats. High levels of 2-DG metabolic activity were observed within the cortical hind limb area, ventral posterolateral thalamic nucleus, and posterior thalamic nucleus contralateral to the ligated sciatic nerve, and these levels were higher than ipsilateral corresponding regions in CCI rats. In addition, patterns of increased neural activity found in the brain of CCI rats showed some similarities and differences to those found in the brain of rats exposed to acute nociception induced by noxious heat or formalin stimulation. Thus, these CCI-induced spontaneous increases in neural activity within extensive brain regions of CCI rats previously implicated in sensory-discriminative and affective-motivational dimensions of pain as well as centrifugal modulation of pain are likely to reflect brain neural processing of spontaneous pain. Implications of increased brain neural activity in mechanisms of neuropathic pain are discussed with emphasis on correlations between spatial patterns of altered brain neural activity and pain-related behaviors in CCI rats and clinical symptoms in neuropathic pain patients.
Mao
J
J
Department of Anesthesiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Mayer
D J
DJ
Price
D D
DD
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D003250:Constriction; D003847:Deoxyglucose / Q000378:metabolism; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003847:Deoxyglucose