Local treatment with the N-methyl-d-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action

Due to the recent discovery of peripheral N-methyl-D-aspartate (NMDA) (and other glutamate) receptors in animal studies, the NMDA receptor antagonist, ketamine (0.83 mg/ml, 6 ml) or saline was injected s.c. preinjury in 10 healthy volunteers, to study the effect on burn-induced primary and secondary hyperalgesia. On the saline treated leg, all subjects developed primary hyperalgesia and secondary hyperalgesia. On the contralateral leg treated with ketamine, there was a significant reduction of primary hyperalgesia and an inhibition of development of secondary hyperalgesia. In an experimental day 2, lidocaine temporarily blocked the development of primary and secondary hyperalgesia. When saline was injected in the contralateral leg treated with ketamine 1 week previously (n = 6), no zone of secondary hyperalgesia was developed. In contrast, subjects (n = 3) treated with ketamine 2 weeks before, reported development of secondary hyperalgesia following saline, a preliminary indication of a long-lasting peripheral action of ketamine.

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