Effect of valdecoxib pretreatment on pain and secondary hyperalgesia: a randomized controlled trial in healthy volunteers [ISRCTN05282752, NCT00260325]

Abstract

Background: Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization - induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers.

Methods: The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped.

Results: The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation.

Conclusion: We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers.

Figure 1

The effect of valdecoxib (40 mg, PO) and placebo on cold- (panel A) and hot (panel B) pain threshold. The pain threshold is expressed in °C (mean ± SD). Time scale indicates the time (in min) after study drug or placebo administration and when the pain measurements were performed. Black columns represent valdecoxib administration; white columns represent placebo administration. The results were compared using the Wilcoxon signed ranks test.

Figure 2

The effect of valdecoxib (40 mg, PO) and placebo on algosity (panel A) and unpleasantness (panel B) of the supra-maximal pain stimulus. The pain intensity is expressed in the visual analog scale of pain units (0 = no pain, 100 = maximum pain) as mean ± SD. Time scale indicates the time (in min) after study drug or placebo administration and when the pain measurements were performed. Black columns represent valdecoxib administration; white columns represent placebo administration. The results were compared using the Wilcoxon signed ranks test.

Figure 3

The effect of valdecoxib (40 mg, PO) and placebo on the skin area of allodynia (panel A) and mechanical hyperalgesia (panel B) after skin heat/capsaicin sensitization performed 120 min after study drug or placebo administration. The areas of allodynia (response to paint brush stimulation) and mechanical hyperalgesia (response to von Frey hair stimulation) are expressed as mean ± SD in cm². Time scale indicates the time (in min) after study drug or placebo administration and when the pain measurements were performed. Black columns represent valdecoxib administration; white columns represent placebo administration. The results were compared using the Wilcoxon signed ranks test.