The substance P receptor antagonist CP-99,994 reduces acute postoperative pain

Background Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin‐1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation. Methods The analgesic efficacy of CP‐99,994, a NK1 receptor antagonist, was compared w...

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Published in:Clinical pharmacology and therapeutics 1998-11, Vol.64 (5), p.562-568
Main Authors: Dionne, Raymond A., Max, Mitchell B., Gordon, Sharon M., Parada, Suzan, Sang, Christine, Gracely, Richard H., Sethna, Navil F., MacLean, David B.
Format: Article
Language:English
Subjects:
Acute Disease
Analgesics
Analgesics - pharmacology
Analgesics - therapeutic use
Biological and medical sciences
Double-Blind Method
Humans
Medical sciences
Neurokinin-1 Receptor Antagonists
Neuropharmacology
Pain Measurement
Pain, Postoperative - drug therapy
Pain, Postoperative - metabolism
Pharmacology. Drug treatments
Piperidines - pharmacology
Piperidines - therapeutic use
Time Factors
Tooth Extraction - adverse effects
Treatment Outcome
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Summary:Background Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin‐1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation. Methods The analgesic efficacy of CP‐99,994, a NK1 receptor antagonist, was compared with ibuprofen and placebo in 78 subjects undergoing third molar extraction. The initial 60 subjects randomly received 1 of 3 possible treatments in a double‐blind fashion before oral surgery: 750 μg/kg CP‐99,994 infused intravenously over 5 hours on a tapering regimen starting 2 hours before surgery, 600 mg oral ibuprofen 30 minutes before surgery, or placebo. In a second study, 18 subjects were randomized to the same regimens starting 30 minutes before surgery to maximize the amount of CP‐99,994 circulating during pain onset. Results In the first study, ibuprofen significantly reduced pain, as measured by visual analog scale, from 90 to 240 minutes postoperatively compared with placebo. CP‐99,994 produced analgesia that was significant at 90 minutes (P < 0.01 compared with placebo), but not at subsequent time points. In the second study, ibuprofen and, to a lesser extent, CP‐99,994 significantly suppressed pain in comparison to placebo at 60, 90, and 120 minutes (P < 0.05). The incidence of side effects was similar across groups. Conclusions This replicate demonstration that a NK1 receptor blocker relieves clinical pain supports the hypothesis that substance P contributes to the generation of pain in humans. The reduction in postoperative pain at doses not producing side effects suggests that NK1 antagonists may be clinically useful. Clinical Pharmacology & Therapeutics (1998) 64, 562–568; doi:
ISSN:0009-9236
1532-6535
DOI:10.1016/S0009-9236(98)90140-0