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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1835-1846
Number of pages12
JournalPain
Volume160
Issue number8
DOIs
StatePublished - Aug 1 2019

Fingerprint

Peripheral Nervous System Diseases
Cross-Over Studies
Placebos
Drug Therapy
oxaliplatin
Pain
Pain Threshold
docetaxel
Neuralgia
Foot
Pregabalin
Paclitaxel
Analgesics
Animal Models
Ligands
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy : A randomized, placebo-controlled, crossover study. / Hincker, Alexander; Frey, Karen; Rao, Lesley; Wagner-Johnston, Nina; Abdallah, Arbi Ben; Tan, Benjamin; Amin, Manik; Wildes, Tanya; Shah, Rajiv; Karlsson, Pall; Bakos, Kristopher; Kosicka, Katarzyna; Kagan, Leonid; Haroutounian, Simon.

In: Pain, Vol. 160, No. 8, 01.08.2019, p. 1835-1846.

Research output: Contribution to journalArticle

Hincker, A, Frey, K, Rao, L, Wagner-Johnston, N, Abdallah, AB, 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
Hincker, Alexander ; Frey, Karen ; Rao, Lesley ; Wagner-Johnston, Nina ; Abdallah, Arbi Ben ; Tan, Benjamin ; Amin, Manik ; Wildes, Tanya ; Shah, Rajiv ; Karlsson, Pall ; Bakos, Kristopher ; Kosicka, Katarzyna ; Kagan, Leonid ; Haroutounian, Simon. / Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy : A randomized, placebo-controlled, crossover study. In: Pain. 2019 ; Vol. 160, No. 8. pp. 1835-1846.
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abstract = "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.",
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