Mechanisms of pain in nonmalignant disease

To review key mechanisms underlying the transmission of nociceptive information from the periphery to the central nervous system implicated in different acute pain states.

Advances in molecular and transgenic approaches have helped to identify novel therapeutic targets for the treatment of pain from tissue and nerve damage such as acid-sensing ion channels, transient receptor potential and NaV channels. The subsequent development of selective pharmacological ligands has also strengthened the role of other receptors such as hyperpolarization-activated cyclic nucleotide-gated channels and the further development of subunit specific antagonists, such as those available for NR2B, will further advance our understanding of the mechanisms involved in nociceptive transmission.

Inflammatory and neuropathic pain differ considerably in their peripheral mechanisms but certain central spinal and brain mechanisms are common to both. The mechanisms of pain are not fully established but are thought to be underpinned by changes in the expression of receptors (nociceptive plasticity), central spinal hyperexcitability (central sensitization) and alterations in descending control from the midbrain. This review considers these mechanisms and highlights recent advances in the understanding of pain perception.