Antihyperalgesic and analgesic properties of the N-methyl-d-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia
Article first published online: 9 JAN 2012
2008 European Federation of Chapters of the International Association for the Study of Pain
European Journal of Pain
Volume 12, Issue 1, pages 17–29, January 2008
How to Cite
Klein, T., Magerl, W., Hanschmann, A., Althaus, M. and Treede, R.-D. (2008), Antihyperalgesic and analgesic properties of the N-methyl-d-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic hyperalgesia. European Journal of Pain, 12: 17–29. doi: 10.1016/j.ejpain.2007.02.002
- Issue published online: 9 JAN 2012
- Article first published online: 9 JAN 2012
- Received 24 October 2006; Revised 29 January 2007; accepted 10 February 2007
- Central sensitization;
- Secondary hyperalgesia;
- Wind up;
NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters.
We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. Furthermore, we tested the effect on pain summation (wind up). Eighteen healthy subjects received either a single dose of neramexane (40mg p.o.), flupirtine (100mg) or placebo in a double-blind, randomized, cross-over study.
Pain evoked by intradermal capsaicin injection as well as pain evoked by pinpricks was significantly reduced by neramexane (−22% to −30% vs. placebo) in the non-sensitized skin indicating a marked analgesic effect. Moreover, dynamic mechanical allodynia (pain to light touch) was also significantly attenuated by neramexane (−28% vs. placebo). However, static secondary hyperalgesia to pinprick stimuli after capsaicin injection was not significantly reduced (−9% vs. placebo). Flupirtine showed no analgesic or anti-hyperalgesic effect. Mechanically-evoked wind up of pain sensation was not affected by any treatment.
The results suggests that in a human surrogate model of neurogenic hyperalgesia a single low-dose of neramexane had a marked analgesic effect in the sensitized and in the non-sensitized state and thus may be a useful drug to treat the enhanced pain sensitivity in neuropathic pain patients. Its efficacy may be based on analgesia rather than anti-hyperalgesia or anti-windup. In contrast, flupirtine showed neither an analgesic nor an anti-hyperalgesic effect at a dose used for the treatment of postoperative pain.