The Role of PET Scan in Conscious Rats With Neuropathic Pain: Differential Changes in Brain Glucose Metabolic...

Neuropathic pain is caused by lesions in the somatosensory nervous system. Pain occurs spontaneously, and responses to noxious and innocuous stimuli are pathologically amplified. Despite the abundant functional magnetic resonance imaging studies in awake human subjects, there is no available report on the behavioral correlate of differential brain areas involved in spontaneous and evoked pain symptoms in a conscious animal model. We investigated whether positron emission tomography (PET) imaging could depict the spatial changes in glucose metabolic activity in the awake male rat brain during spontaneous- and evoked-pain conditions on a spared nerve injury (SNI) model of neuropathic pain.

Two major branches of the sciatic nerve, the tibial and common peroneal nerves, were transected under anesthesia. Two PET experiments were performed. In the spontaneous pain behavior group, abnormal paw-lifting behaviors were recorded during fluorodeoxyglucose (FDG) uptake. In the allodynia group, the ipsilateral side of the lesion hindpaw was stimulated with a 6-g von Frey fi lament once every 5 seconds for 20 minutes during FDG uptake. Each rat was scanned twice in both experiments: once before and once from 3 to 7 days after SNI surgery. Nerves were isolated but not transected in the sham-operated control group.

After SNI surgery, rats displayed spontaneous jerky paw lifting and mechanical sensitization lasting at least 4 weeks. In the spontaneous pain behavior group, glucose metabolic activity in the SNI condition significantly increased in the ipsilateral posterior insular cortex (PIC) compared to pre-surgery and the sham-operated controls. The glucose metabolic activity of the PIC was linearly correlated with the frequency of spontaneous paw lifting. In the allodynia group, changes in glucose metabolic activities in the SNI condition significantly increased in the bilateral primary somatosensory cortex, contralateral secondary somatosensory cortex, contralateral primary motor cortex, ipsilateral secondary motor cortex, ipsilateral rostral insular cortex, PIC, hypothalamus, medial thalamus (including the medial dorsal nucleus and anterior periventricular thalamic nucleus), and medial cerebellum.

Differential brain areas in rats with peripheral neuropathic pain were activated between mechanical hypersensitivity and spontaneous pain-related behaviors. The data suggest that PET is a useful imaging technique to establish the link between behavioral correlates and topographical representation in awake rats suffering from spontaneous pain and allodynia of neuropathic pain.