Páll Karlsson

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Alexander Hincker, Washington University Pain Center, Washington University in St. Louis School of Medicine, St Louis, MO, 63110, USA.
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  • Karen Frey, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO.
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  • Lesley Rao, Washington University Pain Center, Washington University in St. Louis School of Medicine, St Louis, MO, 63110, USA.
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  • Nina Wagner-Johnston, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore
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  • Arbi Ben Abdallah, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO.
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  • Benjamin Tan, Division of Genomics & Bioinformatics, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
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  • Manik Amin, Division of Genomics & Bioinformatics, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
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  • Tanya Wildes, Division of Genomics & Bioinformatics, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
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  • Rajiv Shah, Washington University Pain Center, Washington University in St. Louis School of Medicine, St Louis, MO, 63110, USA.
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  • Pall Karlsson
  • Kristopher Bakos, Investigation Drug Service, Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO.
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  • Katarzyna Kosicka, Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland.
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  • Leonid Kagan, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ.
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  • Simon Haroutounian, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO., Washington University Pain Center, Washington University in St. Louis School of Medicine, St Louis, MO, 63110, USA.

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold (MPT) at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin versus placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in cross-over design. Twenty-three participants were eligible for efficacy analysis. MPT was not significantly correlated with reduction in average pain (P = 0.97) or worst pain (P = 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post-hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% versus 14.6%, P = 0.04). In summary, baseline MPT tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.

OriginalsprogEngelsk
TidsskriftPain
ISSN0304-3959
DOI
StatusE-pub ahead of print - 6 apr. 2019

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