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 (40 mg p.o.),
flupirtine (100 mg) 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.