*2.2. Thalamus*

While the thalamus is like a relay station for nociceptive information, it also likely performs important computations on afferent nociceptive information. The most obvious way this could occur is by regulating cortical excitability via its activity or connectivity. Thalamic lesions in experimental

animals seem to support this role, causing moderate changes in pain aversion behavior [45]. Correlative data from human subjects appear to accord with this role. Subjects with neuropathic pain had decreased blood oxygenation level–dependent activity and gray matter volume in the contralateral thalamus [46]. Furthermore, thalamic connectivity to the cortex is also reduced in patients with chronic pain, which may result in the reduced cortical gray matter [47,48].

A series of important papers on how human thalamic neurons are involved with pain were carried out by Lenz et al. in the 1980s and 1990s [49–54]. These included recording neuronal activity in the human principal sensory nucleus of the thalamus and microstimulating ventral thalamic neurons in patients undergoing implantation of DBS electrodes. Microstimulating [55,56] the human thalamic nucleus ventralis caudalis (Vc) in these patients caused acute thermal pain [51]. Neurons in the Vc also respond to specific types of painful stimuli in a graded fashion [50], which provides strong evidence that that pain information is organized somatotopically and by the type of nociceptor.

Even more importantly, some of these recordings were in patients experiencing chronic pain. The thalamic neurons in a patient with post-amputation dea fferentation pain demonstrated bursting activity. Bipolar microstimulation of these neurons at 0.3 mA caused a burning pain, similar to the qualitative aspects of patients' chronic pain, although the location was di fferent [49]. No sensations were describable at currents of 1.0 mA. Brief periods of stimulation with implanted chronic macroelectrodes caused a burning or tingling sensation with e ffective pain control for at least two years. Comparing thalamic recordings from multiple patients with amputations and control patients who were undergoing DBS for movement disorders showed a much larger thalamic homunculus than the corresponding region in these control patients. The same area also exhibited altered excitability [52]. These results further support the role of the thalamus in modulating excitability in the cortical pain network. Thalamic excitability and organization are related to chronic pain [53].
