ABSTRACT

Hyperalgesia is an increased sensitivity to noxious stimuli. Allodynia refers to pain evoked by previously non-noxious or subthreshold stimuli. Primary hyperalgesia is increased sensitivity within the area of injury and is produced by changes in peripheral nociceptor function. Secondary hyperalgesia occurs in undamaged skin around an injury site and is due to centrally mediated changes in sensitivity. Nerve growth factor is the preferred ligand for trkA, brain-derived neurotrophic factor and neurotrophin-4/5 for trkB, and neurotrophin-3 has the highest affinity for trkC. Interactions between nociceptive mechanisms and the immune system are possible at multiple sites in the peripheral and central nervous system, and can have a major influence on inflammatory hyperalgesia. Inflammation induces increased sensitivity within nociceptive pathways, both in the peripheral and central nervous system. Understanding the mechanisms of inflammatory hyperalgesia is essential for further identification of effective and potentially novel analgesic targets.