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

Alexander Hincker; Karen Frey; Lesley Rao; Nina Wagner-Johnston; Arbi Ben Abdallah; Benjamin Tan; Manik Amin; Tanya Wildes; Rajiv Shah; Pall Karlsson; Kristopher Bakos; Katarzyna Kosicka; Leonid Kagan; Simon Haroutounian

doi:10.1097/j.pain.0000000000001577

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

Alexander Hincker, Karen Frey, Lesley Rao, Nina Wagner-Johnston, Arbi Ben Abdallah, Benjamin Tan, Manik Amin, Tanya Wildes, Rajiv Shah, Pall Karlsson, Kristopher Bakos, Katarzyna Kosicka, Leonid Kagan, Simon Haroutounian

Department of Clinical Medicine - Core Centre for Molecular Morphology, Section for Stereology and Microscopy

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

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 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 = 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% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.

Original language	English
Journal	Pain
Volume	160
Issue	8
Pages (from-to)	1835-1846
Number of pages	12
ISSN	0304-3959
DOIs	https://doi.org/10.1097/j.pain.0000000000001577
Publication status	Published - Aug 2019

Keywords

Chemotherapy-induced peripheral neuropathy
Docetaxel
Mechanical pain threshold
Oxaliplatin
Paclitaxel
Pregabalin
Quantitative sensory testing

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Somatosensory_predictors_of_response_to_pregabalin.16Final published version, 482 KBLicence: CC BY-NC-ND

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Hincker, A., Frey, K., Rao, L., Wagner-Johnston, N., Ben Abdallah, A., Tan, B., Amin, M., Wildes, T., Shah, R., Karlsson, P., Bakos, K., Kosicka, K., Kagan, L., & Haroutounian, S. (2019). Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study. Pain, 160(8), 1835-1846. https://doi.org/10.1097/j.pain.0000000000001577

@article{9e9e287ff6ca42b7b7a145a56897d009,

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

abstract = "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 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 = 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% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.",

keywords = "Chemotherapy-induced peripheral neuropathy, Docetaxel, Mechanical pain threshold, Oxaliplatin, Paclitaxel, Pregabalin, Quantitative sensory testing",

author = "Alexander Hincker and Karen Frey and Lesley Rao and Nina Wagner-Johnston and {Ben Abdallah}, Arbi and Benjamin Tan and Manik Amin and Tanya Wildes and Rajiv Shah and Pall Karlsson and Kristopher Bakos and Katarzyna Kosicka and Leonid Kagan and Simon Haroutounian",

year = "2019",

month = aug,

doi = "10.1097/j.pain.0000000000001577",

language = "English",

volume = "160",

pages = "1835--1846",

journal = "Pain",

issn = "0304-3959",

publisher = "Lippincott Williams and Wilkins",

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Hincker, A, Frey, K, Rao, L, Wagner-Johnston, N, Ben Abdallah, A, Tan, B, Amin, M, Wildes, T, Shah, R, Karlsson, P, Bakos, K, Kosicka, K, Kagan, L & Haroutounian, S 2019, 'Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study', Pain, vol. 160, no. 8, pp. 1835-1846. https://doi.org/10.1097/j.pain.0000000000001577

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study. / Hincker, Alexander; Frey, Karen; Rao, Lesley et al.
In: Pain, Vol. 160, No. 8, 08.2019, p. 1835-1846.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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 - Ben Abdallah, Arbi

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

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 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 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 = 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% vs 14.6%, P = 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 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 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 = 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% vs 14.6%, P = 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

U2 - 10.1097/j.pain.0000000000001577

DO - 10.1097/j.pain.0000000000001577

M3 - Journal article

C2 - 31335651

SN - 0304-3959

VL - 160

SP - 1835

EP - 1846

JO - Pain

JF - Pain

IS - 8

ER -

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

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