Ricerc@Sapienza

Background. Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/
or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent l-opioid agonist,
reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The
pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In
this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in
patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia.
Methods. Sixty-four patients, undergoing remifentanil infusion during general anaesthesia andmajor lung surgery, were randomly
assigned to receive either buprenorphine i.v. infusion (25lg h1 for 24h) ormorphine (equianalgesic dose) perioperatively. The
presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative
pain scores, opioid consumption and postoperative neuropathic pain assessed one and threemonths postoperatively.
Results. A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control
group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the
buprenorphine-treated group than in the morphine-treated group: 18 vs 9min (P¼0.002). At 30min postoperatively, patients
receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine
(P¼0.009). At three months, no differences between groups were noted.
Conclusions. Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical
incision but shows no long-term efficacy at three months follow-up.