Peripheral analgesia: Hitting pain where it hurts.

Pain is a complex biological phenomenon that encompasses intricate neurophysiological, behavioural, psychosocial and affective components. Protracted or chronic pain alerts an individual to a possible pathological abnormality and is the main reason why patients visit a primary care physician. Despite the pervasiveness of chronic pain in the population, the effectiveness of current pharmacological therapies remains woefully inadequate and prolonged treatment often leads to the development of undesirable side-effects. Since the vast majority of chronic pain originates in a specific tissue or group of tissues, it may be advantageous to target pain control in the periphery and thereby circumvent the known risks associated with non-specific systemic treatments. This review spotlights a number of promising targets for peripheral pain control including the transient receptor potential (TRP) family of neuronal ion channels, the family of proteinase activated receptors (PARs), cannabinoids, and opioids. A critical appraisal of these targets in preclinical models of disease is given and their suitability as future peripheral analgesics is discussed.