Topical
analgesics are widely marketed for treatment of muscle and
joint pain. We have recently developed a model of
muscle pain and have used this model to evaluate the efficacy of commercially available topical and peroral
ketoprofen in order to evaluate the time- and dose-dependence of
analgesia. In the present study, we examined the dose- (0, 50, and 100 mg) and time-dependence (hourly to 8 h) of commercially available peroral and topical
ketoprofen. In order to achieve infusion times of 8 h (and thus study the time course of
analgesic action), we adapted the model of low pH-induced
muscle pain in humans to these requirements by applying the infusions continuously for 10 min every hour for 8 h. We found that the 10 min infusion produced reliable and consistent
pain levels that were reproducible over the 8 h of the study. The study was performed double-blind, randomized, and with a 1-week interval between each of five different sessions (cross-over). Altogether six volunteers underwent intramuscular infusions of isotonic
phosphate-buffered
saline solution of pH 5.2; during each 8 h session the infusion was switched on eight times with a duration of 10 min at 50 min intervals (there was no infusion during the 50 min interval). The intramuscular infusion of low pH
phosphate buffer induced a localized dull-aching or stinging
muscle pain sensation; the flow rate of the pH infusion was individually adjusted to induce
pain of a magnitude of 20% on a visual analogue scale (ranging from "no
pain" (0%) to "unbearable
pain" (100%)). Twenty minutes after starting the infusion the volunteers received a
capsule with either a placebo or 50 or 100 mg
ketoprofen perorally and, in addition, either placebo gel or 50 or 100 mg of a 2.5% commercial
ketoprofen gel was applied topically to the skin. One of the sessions included a placebo gel and an oral placebo. The intensity of the recurrent
pain stimulus was significantly reduced by 59% following administration of 100 mg peroral
ketoprofen within the first 3 h (P<0.03, Wilcoxon test); this
analgesia lasted up to the sixth hour of the experimental protocol. Oral
ketoprofen (50 mg) was less effective and reduced the
pain intensity by 45% (P<0.05) from only the second to the third hour. In contrast,
pain reduction after topical
ketoprofen application was not of the same magnitude but appeared to be faster to develop (with a maximum effect within 1 h) on average. The maximum
pain suppression with 100 mg topical 2.5%
ketoprofen gel was by 51% (significant with P<0.03), while 50 mg topical
ketoprofen produced a non-significant reduction of 29%. The apparent
analgesia was rapid to develop but transient and
pain ratings increased back to baseline values within 3 h for the 100 mg dose and within 2 h for the 50 mg dose. This data suggests that topical application of commercial gel-based systems does not provide long-lasting
analgesia in the muscle when compared to perorally-dosed
ketoprofen. In addition, the data show that even doses of 100 mg peroral
ketoprofen do not provide complete relief of
muscle pain.