The center median-parafascicular (CM-Pf) complex, which constitutes the major portion of the intralaminar thalamus in man, has long been known to be involved in the processing of pain under normal and pathological conditions. Yet, these ‘forgotten’ nuclei with their rich connectivity to other thalamic nuclei, the basal ganglia and cortical areas have received only relatively little attention over the past two decades. With regard to the recent reinterest in functional stereotactic neurosurgery as a treatment option for chronic refractory pain, the CM-Pf complex has been reconsidered as a target. This review provides a systematic overview on the current knowledge about the anatomy and connectivity of the CM-Pf complex, neurophysiological studies, and on concepts of its role in pain processing under various conditions. We also review the previous experience with ablative surgery and deep brain stimulation of the CM-Pf complex. Studies in men and experimental animals indicate that the CM-Pf complex is part of a medial pain system, which appears to be involved primarily in affective and motivational dimensions of pain. Single-unit recordings from the CM-Pf complex have shown that the activity of CM-Pf cells is modified by painful stimuli. Under pathological conditions, bursting firing patterns and altered discharge rates were found. Thalamotomies targeting at the CM-Pf complex yielded beneficial results for chronic pain, but interpretation of the results is limited. With bifocal deep brain stimulation, short-term effects of CM-Pf stimulation were superior to those of somatosensory thalamic stimulation in neuropathic pain. There is evidence, that the CM-Pf complex might also be involved in the mediation of the beneficial effects of somatosensory thalamic stimulation and periventricular grey stimulation.

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