TY - JOUR
T1 - Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy
T2 - A randomized, placebo-controlled, crossover study
AU - Hincker, Alexander
AU - Frey, Karen
AU - Rao, Lesley
AU - Wagner-Johnston, Nina
AU - Abdallah, Arbi Ben
AU - Tan, Benjamin
AU - Amin, Manik
AU - Wildes, Tanya
AU - Shah, Rajiv
AU - Karlsson, Pall
AU - Bakos, Kristopher
AU - Kosicka, Katarzyna
AU - Kagan, Leonid
AU - Haroutounian, Simon
N1 - Publisher Copyright:
Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
PY - 2019/8
Y1 - 2019/8
N2 - Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca21 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 at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs 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 crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P 5 0.97) or worst pain (P 5 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 5 0.23) or worst pain (29.2% vs 16.0%, P 5 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n 5 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P 5 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.
AB - Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca21 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 at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs 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 crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P 5 0.97) or worst pain (P 5 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 5 0.23) or worst pain (29.2% vs 16.0%, P 5 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n 5 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P 5 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.
KW - Chemotherapy-induced peripheral neuropathy
KW - Docetaxel
KW - Mechanical pain threshold
KW - Oxaliplatin
KW - Paclitaxel
KW - Pregabalin
KW - Quantitative sensory testing
UR - http://www.scopus.com/inward/record.url?scp=85070466297&partnerID=8YFLogxK
U2 - 10.1097/j.pain.0000000000001577
DO - 10.1097/j.pain.0000000000001577
M3 - Article
C2 - 30985627
AN - SCOPUS:85070466297
SN - 0304-3959
VL - 160
SP - 1835
EP - 1846
JO - Pain
JF - Pain
IS - 8
ER -