Differential effects of spinal (R)-ketoprofen and (S)-ketoprofen against signs of neuropathic pain and tonic nociception: evidence for a novel mechanism of action of (R)-ketoprofen against tactile allodynia

The spinal activity of racemic ketoprofen and its enantiomers in models of neuropathic and tonic pain was explored in rats. Tactile allodynia and ther mal hyperalgesia were induced by tight ligation of the L-5/L-6 spinal nerve s. Tonic pain was modeled by the formalin-induced flinch response. The spin al injection of (S)-ketoprofen alone or of morphine alone did not produce a ntiallodynic activity. A 1:1 combination of these drugs produced a robust d ose-dependent antiallodynic action, consistent with previous observations w here (S)ketorolac combined with morphine also produced antiallodynia. (R)-k etoprofen given alone spinally produced a dose-dependent antiallodynia, but its activity was not augmented by spinal morphine. Conversely, (S)-ketopro fen, but not (R)-ketoprofen, blocked the second phase of the formalin-induc ed flinch response; neither enantiomer significantly blocked phase one of t he formalin response. Again, (S)-, but not (R)-ketoprofen, interacted syner gistically with spinal morphine in suppressing the phase II formalin respon se. These results are consistent with a spinal COX inhibitory action of (S) -ketoprofen. These results also point to a novel, as yet undefined, mechani sm of action of (R)ketoprofen against signs of neuropathic pain that does n ot appear to; involve COX inhibition. The ability to modulate tactile allod ynia is of special interest as this represents an aspect of clinical neurop athic pain that is very difficult to treat adequately. (C) 2000 Internation al Association for the Study of Pain. Published by Elsevier Science B.V. Al l rights reserved.