Positive Feedback Mechanisms in Pain Modulation and Chronic Pain.

Feedback controls play important roles in biological systems, from the cellular level to systemic levels. Positive and negative feedback are two major feedback mechanisms. In this review, I will mainly investigate the positive feedback system involved in pain transmission, modulation and plasticity. At the level of the spinal cord, descending facilitation from different regions of supraspinal structures exert facilitatory effects on spinal nociceptive transmission. At the level of the cortex, positive feedback at synaptic and cellular levels contribute to long-term potentiation (LTP) of synaptic transmission. Several key signalling pathways for positive feedback will be discussed, in particular, NMDA receptor-adenylyl cyclase subtype 1 (AC1)-dependent signalling pathways. Finally, at both physiological and pathological points of view, the importance of positive feedback in chronic pain will be discussed.