Acetaminophen and chronic post-surgical neuropathic pain: a randomized double blind cross-over study

OBJECTIVE: Despite not being recommended in treatment algorithms, people often take acetaminophen for pain relief in neuropathic pain. As there is no randomized clinical trial on oral acetaminophen in neuropathic pain, this study aims to evaluate the efficacy of oral therapeutic-dose acetaminophen compared to placebo in patients with peripheral neuropathic pain. DESIGN: This is a randomized, placebo-controlled, crossover, double-blind clinical study. The protocol and informed consent form were approved by the French Research Ethics Committee and National Drug Agency (trial number: NCT03559985). SETTING: It took place in University Hospital, Clermont-Fd, France. SUBJECTS: Thirty patients with chronic post-surgery neuropathic pain were randomised. METHODS: Acetaminophen or placebo was taken for 7 days with a wash-out period of 7 days and treatments were compared. Outcomes were 7-day mean pain intensity (numerical rating scale) after treatment, Neuropathic Pain Symptom Inventory (NPSI), Patient Global Impression of Change (PGIC), Hospital Anxiety and Depression Scale (HAD), Pittsburgh Sleep Quality Index (PSQI), and adverse events. RESULTS: Acetaminophen presents no statistical difference with the placebo for pain report (effect-size [95%CI]: -0.09 [-0.45; 0.26], P = 0.607) and for all secondary outcomes. CONCLUSIONS: This study demonstrates no clinically meaningful analgesic benefit of short-term, 3g/day oral acetaminophen as add-on therapy in chronic post-surgical peripheral neuropathic pain, and no adverse events. Although findings should not be generalized, patients with neuropathic pain using self-medicated acetaminophen should always be informed about the risks of long-term use of acetaminophen to avoid unnecessary intake and potential long term adverse events.