Memantine before Mastectomy Prevents Post-Surgery Pain: A Randomized, Blinded Clinical Trial in Surgical Patients

Abstract

BackgroundNeuropathic pain following surgical treatment for breast cancer with or without chemotherapy is a clinical burden and patients frequently report cognitive, emotional and quality of life impairment. A preclinical study recently showed that memantine administered before surgery may prevent neuropathic pain development and cognitive dysfunction. With a translational approach, a clinical trial has been carried out to evaluate whether memantine administered before and after mastectomy could prevent the development of neuropathic pain, the impairment of cognition and quality of life.MethodA randomized, pilot clinical trial included 40 women undergoing mastectomy in the Oncology Department, University Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) was administered for four weeks starting two weeks before surgery. The primary endpoint was pain intensity measured on a (0–10) numerical rating scale at three months post-mastectomy.ResultsData analyses were performed using mixed models and the tests were two-sided, with a type I error set at α = 0.05. Compared with placebo, patients receiving memantine showed at three months a significant difference in post-mastectomy pain intensity, less rescue analgesia and a better emotional state. An improvement of pain symptoms induced by cancer chemotherapy was also reported.ConclusionsThis study shows for the first time the beneficial effect of memantine to prevent post-mastectomy pain development and to diminish chemotherapy-induced pain symptoms. The lesser analgesic consumption and better well-being of patients for at least six months after treatment suggests that memantine could be an interesting therapeutic option to diminish the burden of breast cancer therapy.Trial RegistrationClinicaltrials.gov NCT01536314

Localized neuropathic pain: an expert consensus on local treatments

“…The mechanisms involved in NP are complex and involve both peripheral and central pathophysiological phenomenon, cross talk between A and C fibers and sensitization after injury, formation of ectopic neuronal pacemakers with abnormal or dysfunctional sodium channels, expression of novel ion channels or receptors, activation of several signaling pathways that mediate the induction and maintenance of NP through transcriptional and posttranslational mechanisms. 3 NP negatively impacts the quality of life and aggravates functional decline. 4 , 5 It is characterized by clinical manifestations that are present across different NP conditions, and its prevalence is nearly 10% in the general population.…”

Memantine for the treatment of general neuropathic pain: a narrative review

“…For the first time, memantine has been shown to be a successful option to prevent pain and pain-associated psychological impairment. Preclinical findings showed that central sensitization was aborted by giving memantine a few days before surgery in an NP model of spinal nerve ligation [37], and was confirmed in patients undergoing mastectomy [72]. The suggestion that memantine may induce sensori-limbic dissociation, to explain the paradox of presence of NP and patients' indifference to it, gives this drug a supplementary property, protecting not only against pain sensitization but also against pain-induced emotional alteration.…”

A Comparative Study on the Efficacy of Oral Memantine and Placebo for Acute Postoperative Pain in Patients Undergoing Dacryocystorhinostomy (DCR)

“…Morel et al ( 15 ) examined the effect of memantine on the reduction of postoperative pain in mastectomy. In this study, memantine was administered at a dose of 5 to 20 mg daily after mastectomy for two weeks.…”

“…Some studies have shown that memantine is able to prevent postoperative pain if administered prior to nerve injuries. However, it is crucial to carry out further RCT studies in homogeneous groups of patients to explore the therapeutic potential of memantine for relieving postoperative pain ( 9 , 15 , 16 ).…”