Preemptive Analgesia

Development of central sensitization and hyperexcitability occurs after surgical incision and results in the amplification of postoperative pain. Preventing the establishment of altered central processing by analgesic treatment may result in short-term (e.g., reduction in postoperative pain and accelerated recovery) and long-term (e.g., reduction in chronic pain and improvement in HRQL^[40] ) benefits during a patient's convalescence. Although experimental studies convincingly confirm the concept of preemptive analgesia in decreasing postinjury pain, the results of clinical trials are mixed.^{[11] [42] [43] [44]}

The precise definition of preemptive analgesia is one of the major controversies in this area of medicine and contributes to the question of whether preemptive analgesia is clinically relevant. Definitions of preemptive analgesia include what is administered before surgical incision, what prevents establishment of central sensitization resulting from incisional injury only (i.e., intraoperative period), or what prevents central sensitization resulting from incisional and inflammatory injuries (i.e., intraoperative and postoperative period).^[11] The first two definitions are relatively narrow and may contribute to the lack of a detectable effect of preemptive analgesia in clinical trials. Timing of the intervention^[44] may not be as clinically important as other aspects of preemptive analgesia (i.e., intensity and duration of the intervention). An intervention administered before surgical incision is not necessarily preemptive if it is incomplete or insufficient such that central sensitization is not prevented.^[45] Incisional and inflammatory injuries are important in initiating and maintaining central sensitization. Confining the definition of preemptive analgesia to only the intraoperative (incisional) period may not be clinically relevant or appropriate because the inflammatory response may last well into the postoperative period and continue to maintain central sensitization. Other methodologic and study design issues also may complicate the question of whether preemptive analgesia is clinically relevant.^{[42] [44]}

A variety of agents and techniques^[44] has been used to study preemptive analgesia. Using the broader definition of preemptive analgesia that covers incisional (intraoperative) and inflammatory (postoperative) injuries, the combination of experimental data and positive clinical trials strongly suggests that preemptive analgesia is a clinically relevant phenomenon. Maximal clinical benefit is

2732