Postoperative Hyperalgesia: Its Clinical Importance and Relevance

PAIN after surgery continues to be a major management challenge in clinical practice. In a recent meta-analysis covering some 20,000 patients and 800 publications, Dolin et al. concluded that 41% of all surgical patients still experience moderate to severe acute postoperative pain and that 24% experience inadequate pain relief. Unfortunately, acute postoperative pain control seems not to have substantially improved over the last decade or so. The picture is equally unsatisfactory regarding long-term outcomes, where chronic pain is increasingly identified as a direct consequence of surgical intervention. Recent surveys of chronic pain after surgery demonstrate that this problem is much more common than previously thought, with some types of surgery (e.g., thoracotomy, mastectomy, limb amputation) being associated with chronic pain incidences of more than 50% at 1 yr postoperatively. The past two decades have seen significant improvements in our understanding of the mechanisms underlying nociception and pain. A key insight has been that nervous system processing of nociception and pain is not hardwired, and that the gain of the nervous system can change as a result of noxious sensory inputs or the drugs used to modulate these. Nociception is now well accepted to result in sensitization of the nervous system, i.e., increased sensitivity regarding nociception and pain. Increased pain sensitivity is increasingly recognized as a potential—paradoxical and undesirable—effect of analgesic use to combat surgical pain and nociception, particularly for opioids. In a patient, such hyperexcitability of pain processing is expressed as increased pain for a given stimulus, a phenomenon termed hyperalgesia in the absence of modality shifts. The presence of hyperalgesia has a major impact on primary and secondary pain processing by the brain, with these changes having the potential to be both adaptive and maladaptive. These alterations may be detrimental in the early postoperative period for a number of reasons. First, hyperalgesia tends to increase the amount of pain the patient experiences—an unwanted outcome of itself—because of greater amplification of given noxious inputs. Second, more pain typically means more patient stress in the postoperative period, with the possibility of negative consequences for a variety of complications and outcomes. Finally, abnormal persistence of nervous system sensitization subsequent to nociception, i.e., excitatory neuroplasticity expressed as hyperalgesia and increased pain, is now considered a major candidate mechanism for the development of chronic pain. The reliable diagnosis of hyperalgesia is difficult based on clinical symptoms alone. The very definition of hyperalgesia—more pain accompanying a given stimulus— makes it clear that its detection is based on construction and comparison of stimulus–response curves before and after nociception or drug application. Therefore, the systematic diagnosis and quantification of hyperalgesia requires the formal, serial determination of stimulus dose–response curves under standardized conditions, a process termed quantitative sensory testing (QST). If postoperative hyperalgesia is not diagnosed, it will not be subject to targeted treatment, which fact may—as will be discussed below—be a contributing factor to the lack of substantive progress in postoperative analgesia mentioned above. The purpose of this review is, first, to explain how nociceptive and opioid-induced hyperalgesia may develop in the early postoperative period; second, to provide data indicating that such hyperalgesia can actually occur in clinical practice; third, to weigh the evidence to date supporting the usefulness of hyperalgesia management in the postoperative context; and fourth, to evaluate current knowledge regarding effective treatments of early postoperative hyperalgesia.