High-frequency stimulation in the ventral posterolateral thalamus reverses electrophysiologic changes and hyperalgesia in a rat model of peripheral neuropathic pain

Abstract

Chronic neuropathic pain is associated with long-term changes at multiple levels of the neuroaxis, including in the brain, where electrical stimulation has been used to manage severe pain conditions. However, the clinical outcome of deep brain stimulation is often mixed, and the mechanisms are poorly understood. By means of electrophysiologic methods, we sought to characterize the changes in neuronal activity in the ventral posterolateral nucleus of the thalamus (VPL) in a rat model of peripheral neuropathic pain, and to reverse these changes with low-voltage, high-frequency stimulation (HFS) in the VPL. Extracellular single-unit neuronal activity was recorded in naive rats and in those with sciatic chronic constriction injury (CCI). Seven days after CCI, brush- and pinch-evoked firing, as well as spontaneous firing and afterdischarge, were significantly increased compared to naive rats. Spontaneous rhythmic oscillation in neuronal firing was also observed in rats with CCI. HFS decreased neuronal firing rates in rats with CCI up to ∼50% except for spontaneous activity, whereas low-frequency stimulation had no effect. Compared to naive rats, burst firing properties (burst events, percentage of spikes in burst, and mean interburst time) were altered in rats with CCI, whereas these changes were reversed to near normal after HFS. Thermal hyperalgesia in rats with CCI was significantly attenuated by HFS. Therefore, this study demonstrates that electrical stimulation within the VPL can effectively modulate some nociceptive phenomena associated with peripheral neuropathic pain.