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.