CHAPTER 50: Preemptive Analgesia

INTRODUCTION

The understanding of postoperative pain has evolved greatly during the past half century. Many laboratory investigations have established that peripheral tissue injury during surgery can trigger a prolonged state of spinal cord excitation. A reduction in neuronal thresholds in the central nervous system (CNS) is thought to amplify pain in postsurgical patients. Preemptive analgesia is an antinociceptive treatment targeted to block CNS hyperexcitability and leads to a reduced postoperative pain state. This treatment also has the long-term goals of facilitating rapid return to usual baseline function as well as decreasing the risk of chronic pain. However, despite numerous investigations, the clinical relevance of such treatment remains in controversy.

HISTORY AND BACKGROUND

The modern concept of preemptive analgesia was based on experimental animal studies demonstrating CNS plasticity and sensitization after nociception. It was theorized that postoperative pain is amplified by continuous processing of afferent input. The preemptive administration of antinociceptive treatments aims to alter the processing of this afferent input and in turn reduce postoperative pain.¹

An editorial in the 1980s postulated that (1) a reduction in massive small-fiber input into the CNS during surgery would prevent a central sensitization, and (2) analgesia that is present preoperatively has the potential to render prolonged effects, well beyond the known time frame of drug action.² Consistent with this proposal were experimental data by Woolf and Wall demonstrating that low doses of opioids, given before a painful stimulus, can effectively prevent central sensitization.³ In contrast, much higher doses of opioids are required to suppress an already sensitized spinal cord. Since Wall's editorial, a large number of investigations have been carried out with overall equivocal results. There has been an appreciation for the multiple variables that influence postoperative pain as well as short-term and long-term goals of preemptive analgesia. In the short term, a reduction in pain scores, analgesic consumption (usually opioids) is sought, and in the long run, a quicker return to function and reduction in chronic pain is desired. In the absence of significant preoperative pain, the surgical incision does remain the key stimulus of central sensitization in most operations that triggers multiple mediators, which serve to extend a peripheral and central excited neural state into the postoperative period. Therefore, in the majority of preemptive studies, the preincisional therapy is not continued into the postoperative period.

PATHOPHYSIOLOGY OF POSTINJURY PAIN

PERIPHERAL SENSITIZATION

The establishment of sensitization in the periphery involves the transition of high-threshold nociceptors into ones of low threshold, as induced by the release of various chemicals soon after surgical incision.⁴ At the site of damage, a complex array of inflammatory mediators, as outlined in Table 50-1, is mobilized from injured tissue, and others are delivered by the circulation.⁵ Small-diameter primary afferent neurons, Aδ and C fibers innervating the region of insult, subsequently ...