Effects of preemptive analgesia on pain and cytokine production in the postoperative period

Background: The postoperative period is associated with increased production of proinflammatory cytokines, which are known to augment pain sensitivity, among other effects. In a previous study, the authors found that patients treated with patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory cytokine response in the postoperative period. In the present study, the authors examined whether preemptive analgesia continued with PCEA may further attenuate the proinflammatory cytokine response and reduce pain sensitivity in the postoperative period. They compared cytokine production in two groups of patients, one receiving PCEA, the other receiving preemptive epidural analgesia continued by PCEA. Methods: Female patients hospitalized for transabdominal hysterectomy were randomly assigned to one of two pain management techniques: PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative pain was assessed using the visual analog scale. Blood samples were collected before, 24, 48, and 72 h following surgery. Production of the following cytokines was assessed ex vivo in stimulated peripheral blood mononuclear cells: interleukin (IL)-1β, tumor necrosis factor α, IL-6, IL-1ra, IL-10, and IL-2. Results: Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h postoperatively, compared with patients of the PCEA group. In patients of the PA + PCEA group in the postoperative period, production of IL-1β, IL-6, IL-1ra, and IL-10 was significantly less elevated, while IL-2 production was significantly less suppressed. Conclusions: Proinflammatory cytokines are key mediators of illness symptoms, including hyperalgesia. The present results suggest that preemptive epidural analgesia is associated with reduced postoperative pain and attenuated production of proinflammatory cytokines.