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

• Published in: Pain (Amsterdam) Vol. 160; no. 8; pp. 1835 - 1846
• Main Authors: Hincker, Alexander, Frey, Karen, Rao, Lesley, Wagner-Johnston, Nina, Ben Abdallah, Arbi, Tan, Benjamin, Amin, Manik, Wildes, Tanya, Shah, Rajiv, Karlsson, Pall, Bakos, Kristopher, Kosicka, Katarzyna, Kagan, Leonid, Haroutounian, Simon
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer 01.08.2019
• Subjects: Aged; Analgesics - therapeutic use; Antineoplastic Agents - adverse effects; Cross-Over Studies; Docetaxel - adverse effects; Double-Blind Method; Female; Humans; Male; Middle Aged; Oxaliplatin - adverse effects; Paclitaxel - adverse effects; Pain Threshold - physiology; Peripheral Vascular Diseases - chemically induced; Peripheral Vascular Diseases - drug therapy; Peripheral Vascular Diseases - physiopathology; Predictive Value of Tests; Pregabalin - therapeutic use; Research Paper
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1097/j.pain.0000000000001577

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.