Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat.
We identified long-term (up to 12 weeks), bilateral changes in spontaneous and evoked pain behavior and baseline forebrain activity following a chronic constriction injury (CCI) of the sciatic nerve. The long-term changes in basal forebrain activation following CCI were region-specific and can be divided into forebrain structures that showed either: (1) no change, (2) an increase, or (3) a decrease in activity with regard to the short-term (2 weeks) changes we previously reported. All the rats showed spontaneous pain behaviors that persisted throughout the 12-week observation period, resembling the pattern of change found in four limbic system structures: the anterior dorsal thalamus, habenular complex, and the cingulate and retrosplenial cortices. In contrast, heat hyperalgesia was delayed in onset until 4 weeks following CCI, but then persisted, showing a nearly constant level of increased responsiveness. The forebrain activation that resembles this behavioral pattern of change is found in somatosensory cortex, and in the hypothalamic paraventricular nucleus and the basolateral amygdala. Finally, mechanical allodynia, which was maximal during the first 2 weeks following nerve injury and gradually recovered by the seventh post-operative week uniquely matches the time course of changes in ventrolateral and ventroposterolateral thalamic activity. Our results indicate that peripheral nerve damage results in persistent changes in behavior and resting forebrain systems that modulate pain perception. The persistent abnormalities in the somatosensory cortex and thalamus suggest that the sensory thalamocortical axis is functionally deranged in certain chronic pain states.
Paulson
Pamela E
PE
Neurology Research Laboratories, University of Michigan, Ann Arbor, MI 48105, USA.
Casey
Kenneth L
KL
Morrow
Thomas J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000503:physiopathology*; D016548:Prosencephalon / Q000098:blood supply / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000503:physiopathology; D013995:Time