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Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.

Abstract
The present investigation aimed to elucidate the analgesic efficacy of 30 mg of intravenous orphenadrine citrate (CAS 4682-36-4) in a human pain model. Eighteen healthy female and male subjects were enrolled and received single infusions of 30 mg orphenadrine citrate and matching placebo in two periods which were separated by a 1 week washout period. The study was designed as a randomised, double-blind, placebo-controlled, two-period, cross-over trial. The intended neurogenic inflammation and hyperalgesia were induced by topical, occlusive application of 1% capsaicin solution (INCI: Capsicum frutescens, containing capsaicinoides from Capsicum annuum annuum, CAS 84603-55-4) for 30 min on defined skin areas of the back. The pain response to CO2 laser pulses applied to the capsaicin pre-treated skin was measured by event related Vertex-EEG recordings. This technique allowed studying the influence of orphenadrine citrate on the (central) P2-component and the (peripheral) Ni-component of the pain response (LSEP). Both, orphenadrine citrate and placebo were given as intravenous infusions over 60 min. Orphenadrine citrate exerted a significant reduction in central and peripheral components of the pain response when compared to placebo. The effect on the central component was highly significant and more pronounced than the peripheral effect of the drug. The analgesic effect developed fast, was already present during infusion, was ongoing, and exceeded the observational period of 4 h after start of infusion. In summary, orphenadrine citrate was able to exert an analgesic/anti-hyperalgesic effect in a low-dose paradigm (30 mg dose) which was predominantly due to central/spinal mechanisms in this capsaicin model with laser somatosensory evoked potentials.
AuthorsKlaus Schaffler, Peter Reitmeir
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 54 Issue 10 Pg. 673-9 ( 2004) ISSN: 0004-4172 [Print] Germany
PMID15553107 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
Chemical References
  • Analgesics
  • Antiparkinson Agents
  • Irritants
  • Orphenadrine
  • Capsaicin
Topics
  • Adolescent
  • Adult
  • Analgesics (administration & dosage)
  • Antiparkinson Agents (adverse effects, pharmacology)
  • Capsaicin
  • Double-Blind Method
  • Electroencephalography (drug effects)
  • Evoked Potentials, Somatosensory (drug effects)
  • Female
  • Humans
  • Hyperalgesia (chemically induced, drug therapy)
  • Injections, Intravenous
  • Irritants
  • Lasers
  • Male
  • Middle Aged
  • Orphenadrine (administration & dosage, adverse effects, pharmacology)
  • Pain Measurement (drug effects)
  • Peripheral Nervous System (drug effects)
  • Skin (drug effects)

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