title: Wind-up of spinal cord neurones and pain sensation: much ado about something?
abstract: Wind-up is a frequency-dependent increase in the excitability of spinal cord neurones, evoked by electrical stimulation of afferent C-fibres. Although it has been studied over the past thirty years, there are still uncertainties about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors. However, most drugs capable of reducing the excitability of spinal cord neurones, including opioids and NSAIDs, can also reduce or even abolish wind-up. Thus, other theories involving synaptic efficacy, potassium channels, calcium channels, etc. have also been proposed for the generation of this phenomenon. Whatever the mechanisms involved in its generation, wind-up has been interpreted as a system for the amplification in the spinal cord of the nociceptive message that arrives from peripheral nociceptors connected to C-fibres. This probably reflects the physiological system activated in the spinal cord after an intense or persistent barrage of afferent nociceptive impulses. On the other hand, wind-up, central sensitisation and hyperalgesia are not the same phenomena, although they may share common properties. Wind-up can be an important tool to study the processing of nociceptive information in the spinal cord, and the central effects of drugs that modulate the nociceptive system. This paper reviews the physiological and pharmacological data on wind-up of spinal cord neurones, and the perceptual correlates of wind-up in human subjects, in the context of its possible relation to the triggering of hyperalgesic states, and also the multiple factors which contribute to the generation of wind-up.
authors.affiliation: Departamento de Fisiología, Edificio de Medicina, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain. ffjfhg@alcala.es
authors.forename: J F
authors.initials: JF
authors.lastname: Herrero
authors.forename: J M
authors.initials: JM
authors.lastname: Laird
authors.forename: J A
authors.initials: JA
authors.lastname: López-García
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002415:Cats; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D007249:Inflammation; D017136:Ion Transport / Q000187:drug effects; D008959:Models, Neurological; D009020:Morphine / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology* / Q000503:physiopathology; D013373:Substance P / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014781:Viscera / Q000294:innervation
chemical_list: D000700:Analgesics; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D013373:Substance P; D009020:Morphine