Role of L- and N-type calcium channel blockers in the management of spinal cord injury: a review of the literature for an update on evidence-based treatment.

Sabino Luzzi

Department of Neurosurgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

In spite of an impressive growing of knowledge and insight into the pathophysiologic mechanisms underlying the devastating sequelae of spinal cord injury and an equally great enthusiasm related to the very recent cell-based neuroregenerative approach, today, a lack of robust evidence still exists regarding the neuroprotective counterpart. Historically, based upon their role within the cellular and extra-cellular oxidative stress cascade ultimately leading to secondary damage after spinal cord injury, central nervous system-related calcium channels and their blockers have polarized the attention as potential candidates for neuroprotection.  The goal of the reported study is an evidence-based and updated overall review of the literature regarding the employment of L- and N-type calcium channel blockers in the management of spinal cord injury.  A structured literature search based upon the main online databases, including PubMed/MEDLINE, EMBASE and The Cochrane Library, was performed. Key words were “calcium channel blockers” and “spinal cord injury”. Only the matched articles in English, published in the last 10 years, involving humans and with the best level of evidence were considered. The current role of L- and N-type calcium channel blockers in the context of the treatment of spinal cord injury was investigated. Based upon the evidence, the most recommendable employment for clinical practice was formulated for each type of calcium channel blocker considered. The search returned 172 articles, of which 48 involved humans. Two meta-analysis, 2 systematic reviews and 5 clinical trials, including 2 multicentric, were selected. All the studies but one focused on the effects and safety of pregabalin, an alpha-2-delta subunit ligand acting as an L- and N-type calcium channel blocker. No evidence of neuroprotection regarding calcium channel blockers were found. Conversely, a primary role of pregabalin was widely demonstrated for the treatment of neuropathic pain, mostly on burning-electrical phenotype, allodynia and heat hyperalgesia. A single-center randomized trial also proved the beneficial effects of nicardipine, a selective L-type blocker, on the autonomic dysreflexia. No role is attributable to calcium channel blockers for the prevention of secondary damage related to the acute phase of spinal cord injury. Conversely, they play a key role in the long-term control of post-traumatic symptoms. Pregabalin has proved to be effective and safe in the management of neuropathic pain, justifying its routine use in clinical practice. More evidence is needed to support the employment of nicardipine in the symptomatic treatment of autonomic dysreflexia.