Wind-up of spinal cord neurones and pain sensation: much ado about something?

Wind-up is a frequency-dependent increase in the excitability of spinal cor d neurones, evoked by electrical stimulation of afferent C-fibres. Although it has been studied over the past thirty years, there are still uncertaint ies about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 re ceptors are required to generate wind-up and therefore a positive modulatio n between these two receptor types has been suggested by some authors. Howe ver, most drugs capable of reducing the excitability of spinal cord neurone s, including opioids and NSAIDs, can also reduce or even abolish wind-up. T hus, other theories involving synaptic efficacy, potassium channels, calciu m channels, etc, have also been proposed for the generation of this phenome non. Whatever the mechanisms involved in its generation, wind-up has been i nterpreted as a system for the amplification in the spinal cord of the noci ceptive message that arrives from peripheral nociceptors connected to C-fib res. This probably reflects the physiological system activated in the spina l cord after an intense or persistent barrage of afferent nociceptive impul ses. 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 informatio n in the spinal cord, and the central effects of drugs that modulate the no ciceptive system. This paper reviews the physiological and pharmacological data on wind-up of spinal cord neurones, and the perceptual correlates of w ind-up in human subjects, in the context of its possible relation to the tr iggering of hyperalgesic stales, and also the multiple factors which contri bute to the generation of wind-up. (C) 2000 Elsevier Science Ltd. All right s reserved.