MAPPING OF PUNCTUATE HYPERALGESIA AROUND A SURGICAL INCISION DEMONSTRATES THAT KETAMINE IS A POWERFUL SUPPRESSOR OF CENTRAL SENSITIZATION TO PAIN FOLLOWING SURGERY

Background: Tissue injury induces central sensitization in the spinal cord dorsal horn neurons via mechanisms involving N-methyl-D-aspartate (NMDA) receptors, leading to secondary hyperalgesia. Using punctuate mechanical hyperalgesia as a measure of central sensitization, we exam ined whether induction and maintenance of central sensitization after surgery could be prevented by a low-dose infusion of the NMDA-receptor antagonist ketamine. Methods: Twenty living kidney donors were includ ed in a randomized, double-blind, parallel, two-group study. Before st art of surgery 10 patients received an i.v, bolus of racemic ketamine 0.5 mg . kg(-1), followed by a continuous i.v. infusion of ketamine 2 mu g . kg(-1) . min(-1) for 24 h, thereafter 1 mu g . kg(-1) . min(-1) for another 48 h. The control group received placebo bolus and infusi on. A standard general anaesthesia including fentanyl was used. Patien t-controlled (PCA) i.v. morphine was used for post operative analgesia . Punctuate mechanical hyperalgesia and temporal summation of mechanic al stimuli causing ''wind-up pain'' were measured using von Frey filam ents. Results: The area of punctuate mechanical hyperalgesia was signi ficantly reduced in the ketamine group 1, 3 and 7 d after the operatio n (P<0.01-0 001). ''Wind-up pain'' was also reduced by ketamine (P<0.0 5). PCA morphine consumption and pain intensity (visual analogue scale ) differed between groups only during the first hours after surgery, i n favour of ketamine. The ketamine patients scored significantly highe r on a global satisfaction score. Side-effects were most frequent in t he placebo group. Conclusion: Low-dose i.v. infusion of ketamine durin g and after surgery reduces mechanical punctuate hyperalgesia surround ing the surgical incision. These results indicate that blockade of NMD A receptors prevents the central sensitization caused by nociceptive i nput during and after surgery. (C) Acta Anaesthesiologica Scandinavica 41 (1997).