title: Neuropathic pain: a maladaptive response of the nervous system to damage.
abstract: Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
authors.affiliation: Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA. mcostigan@partners.org
authors.forename: Michael
authors.initials: M
authors.lastname: Costigan
authors.forename: Joachim
authors.initials: J
authors.lastname: Scholz
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D006801:Humans; D009420:Nervous System / Q000378:metabolism / Q000503:physiopathology*; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism / Q000502:physiology; D017288:Pain Threshold / Q000502:physiology*; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000503:physiopathology