[Pre-emptive analgesia]

Pre-emptive analgesia is based on the idea that analgesia initiated before a nociceptive event will be more effective than analgesia commenced afterwards, and that its effects will outlast the pharmacological duration of action of the analgesic used. The idea of pre-emptive analgesia is based upon experimental neurophysiological work demonstrating that afferent nociceptive impulses result in alterations of central nervous 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 (allodynia), increased responses to pain (hyperalgesia), after-discharging or spontaneous activity of dorsal horn neurons (wind-up), and extension of hypersensitivity to unaffected tissues (secondary hyperalgesia). Their biochemical basis is now being unravelled, with excitatory amino acid (e.g. NMDA) and neuropeptide (e.g. substance P) neurotransmitters playing prominent roles. Blockade of these receptors has recently been shown to depress the central sensitisation associated with nociception. Ketamine, a non-competitive NMDA receptor blocker, for example, has been shown modulate postoperative pain in a positive way. Although the existence of central sensitisation is now being clinically demonstrated, studies of pre-emptive analgesia in the surgical context have not revealed clinically significant effects. This is probably because surgical nociception is much longer-lasting, multimodal and intense than its experimental counterparts. Clinical studies have so far only used short-term analgesia. To permit extrapolation from the experimental to the clinical situation, pre-emption in the surgical context must correspond 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.