TNF and major depressive disorder: The studies confirmed that neutralization of the proinflammatory cytokine TNFα rapidly improves the subjective state of the prospective responder RA patients and demonstrated that this improvement is associated with a drastic reduction in nociception-related activity within the brain pain matrix; the latter not only in the structures responsible for the sensory-discriminative component of pain, but importantly to a large extent also in the structures driving its affective-motivational aspect and involved in mood changes, including depression, and memory.