Enhanced excitability of thalamic sensory neurons and slow-wave EEG pattern after stimuli that induce spinal long-term potentiation.

The term "long-term potentiation" (LTP) is classically attributed to molecular and cellular events caused by repetitive stimulation in the hippocampus. LTP is essentially linked to memory, and chronic pain is associated with long-term plasticity. Hence, LTP-like phenomena are thought to be related to chronic pain.

Sandkühler and colleagues championed the method of high-frequency stimulation (HFS) of the sciatic nerve as a model of pain-related LTP in the spinal cord. In this paper, HFS in anesthetized rats caused sensitization of single units in the ventral postero-lateral nucleus (VPL) and enhanced low-frequency EEG rhythmic activity in the parietal cortex. Long-term depression (LTD) by sciatic nerve conditioning (SNC), known to depress spinal LTP, failed to counter these supraspinal changes. One unequivocal conclusion is that peripheral HFS leads to long-term supraspinal changes that are resistant to peripheral nerve SNC. A less cautious interpretation would be that thalamocortical plasticity, secondary to peripheral nerve injury, is uncoupled from spinal plasticity.

Since this study is based on inducing spinal LTP, data showing that HFS, in fact, reliably induced a stable LTP, whereas SNC effectively reversed LTP, would have further validated use of this model. The authors do acknowledge subtle differences between the sensitization of thalamic neurons induced by HFS versus sciatic injury, as shown by our group (Iwata et al., 2011; Saab, 2012; Hains et al., 2006). Moreover, the data do not show recordings from VPL neurons ipsilateral to sciatic HFS: Were those VPL neurons also sensitized? This renders interpretation of the results describing a bilateral increase in cortical power spectra intriguing. Nevertheless, this study is timely in linking presumably spinal LTP to thalamic sensitization and disruption of ongoing cortical rhythms. As the authors suggest, more work is needed to take a comprehensive approach at understanding pain-induced plasticity at multiple levels of the sensory system, simultaneously and in freely behaving animals when possible.