• Neuronal Mechanisms of Chronic Pain Induced by Spinal Cord Injury

      Whitt, Jessica Lucas; Keller, Asaf; Masri, Radi, 1975- (2012)
      Chronic pain develops in most patients who suffer from spinal cord injury (SCI), and manifests as exaggerated responses to painful stimuli (hyperalgesia), pain in response to normally non-painful stimuli (allodynia), and, most commonly, constant spontaneous pain. The mechanisms of SCI-pain have been difficult to identify, though it is hypothesized to develop as a result of thalamic disinhibition. Here we use an electrolytic lesion in the spinal thalamic tract of rats to model SCI-pain. We employ novel behavioral metrics to show that after spinal lesion rats develop both hyperalgesia and spontaneous pain. We tested the hypothesis that these behavioral abnormalities result from reduced inhibition from the zona incerta (ZI) to thalamic nuclei involved in the sensory aspects of pain (the posterior nucleus, PO) and the affective aspects of pain (mediodorsal nucleus, MD). With single unit, extracellular electrophysiological recordings we demonstrate that SCI- pain results from decreased activity in the inhibitory nucleus ZI, which leads to a dramatic increase in spontaneous and evoked neuronal activity in both PO and MD thalamus. We show that SCI-pain can be reduced by stimulating the motor cortex, and demonstrate that this effect occurs through cortical inputs to ZI, thereby enhancing ZI inputs to PO and MD. These results support the hypothesis that SCI-pain results from reduced activity in ZI which corresponds with increased activity in thalamic nuclei involved with both sensory aspects of pain (PO) and affective aspects of pain (MD). Further, they provide evidence that MCS reverses sensory and affective components of pain by activating the incerto- thalamic pathway and highlight a novel pathway for clinical intervention.