PREEMPTIVE ANALGESIA

Pre-emptive analgesia is based on the idea that analgesia initiated be fore a nociceptive event will be more effective than analgesia commenc ed afterwards, and that its effects will outlast the pharmacological d uration of action of the analgesic used. The idea of pre-emptive analg esia is based upon experimental neurophysiological work demonstrating that afferent nociceptive impulses result in alterations of central ne rvous system function. These changes, most easily elicited by C-fibre afferents, particularly affect the spinal dorsal horn. Termed central sensitisation, they are reflected by reduced pain thresholds (allodyni a), increased responses to pain (hyperalgesia), after-discharging or s pontaneous activity of dorsal horn neurons (wind-up), and extension of hypersensitivity to unaffected tissues (secondary hyperalgesia). Thei r biochemical basis is now being unravelled, with excitatory amino aci d (e.g. NMDA) and neuropeptide (e.g. substance P) neurotransmitters pl aying prominent roles. Blockade of these receptors has recently been s hown to depress the central sensitisation associated with nociception. Ketamine, a noncompetitive NMDA receptor blocker, for example, has be en shown modulate postoperative pain in a positive way. Although the e xistence of central sensitisation is now being clinically demonstrated , studies of pre-emptive analgesia in the surgical context have not re vealed clinically significant effects. This is probably because surgic al nociception is much longer-lasting, multimodal and intense than its experimental counterparts. Clinical studies have so far only used sho rt-term analgesia. To permit extrapolation from the experimental to th e clinical situation, pre-emption in the surgical context must corresp ond adequately to the duration and extent of the nociception involved. Studies of pre-emptive analgesia in a clinically relevant form, i.e. where nociception and analgesia are correctly matched, are called for.