Targeting the affective and cognitive aspects of chronic neuropathic pain using basal forebrain neuromodulation: rationale, review and proposal.

Chronic pain is a major health problem in developed countries where it may affect as much as 20% of the adult population. There have been no significant clinical breakthroughs in therapeutic options for persons with chronic neuropathic pain. These limitations underscore the importance of developing new therapies for this disabling pain syndrome. We have reviewed the limitations of the present treatment strategies for chronic pain, neurophysiology of somatosensory transmission and nociception, mechanisms of neuropathic pain, the concept of a "pain matrix" and the "top-down" modulation of pain, and the cognitive affective role in processing of the pain experience. We found that affective and cognitive aspects of pain constitute important considerations in achieving improvements in the outcomes of pain neuromodulation in patients with chronic neuropathic pain. Based on our review, we propose that future novel neuromodulatory therapeutic strategies should be directed at areas in the brain that are involved in the neural mechanisms of reward valuation and appetitive motivation such as nucleus accumbens, ventral tegmental area, and prefrontal cortex.