title: Analgesic profile of peroral and topical ketoprofen upon low pH-induced muscle pain.
abstract: 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.
authors.affiliation: Klinik und Poliklinik für Dermatologie der Universität Bonn, Klinische Dermatophysiologie, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany The Procter & Gamble Company, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040-9462, USA.
authors.forename: Kay H
authors.initials: KH
authors.lastname: Steen
authors.forename: Holger
authors.initials: H
authors.lastname: Wegner
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Meller
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use*; D002021:Buffers; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007592:Joint Diseases / Q000188:drug therapy*; D007660:Ketoprofen / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D015203:Reproducibility of Results
chemical_list: D000700:Analgesics; D002021:Buffers; D007660:Ketoprofen