Abstract
Study designSystematic review.ObjectivesTo evaluate the impact of cannabinoids on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI), with the aim of determining suitability for clinical trials involving SCI patients.MethodsA systematic search was performed in MEDLINE and Embase databases, following registration with PROPSERO (CRD42019149671). Studies evaluating the impact of cannabinoids (agonists or antagonists) on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI were included. Data extracted from relevant studies, included sample characteristics, injury model, neurobehavioural outcomes assessed and study results. PRISMA guidelines were followed and the SYRCLE checklist was used to assess risk of bias.ResultsThe search returned 8714 studies, 19 of which met our inclusion criteria. Sample sizes ranged from 23 to 390 animals. WIN 55,212-2 (n = 6) and AM 630 (n = 8) were the most used cannabinoid receptor agonist and antagonist respectively. Acute SCI models included traumatic injury (n = 16), ischaemia/reperfusion injury (n = 2), spinal cord cryoinjury (n = 1) and spinal cord ischaemia (n = 1). Assessment tools used assessed locomotor function, pain and anxiety. Cannabinoid receptor agonists resulted in statistically significant improvement in locomotor function in 9 out of 10 studies and pain outcomes in 6 out of 6 studies.ConclusionModulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models; however, the risk of bias is unclear in all studies. These results may help to contextualise future translational clinical trials investigating whether cannabinoids can improve pain and locomotor function in SCI patients.
Highlights
Spinal cord injury (SCI) is a traumatic event associated with severe disability and mortality [1]
The aim of this systematic review was to evaluate the effect of cannabinoids on neurobehavioral outcomes in preclinical models of SCI
As aforementioned, a lack of adherence to reporting items on the SYRCLE checklist mean that accurately assessing risk of bias is challenging, and the overall risk of bias and validity of the reported outcomes remain unclear
Summary
Spinal cord injury (SCI) is a traumatic event associated with severe disability and mortality [1]. Prevalence of SCI is estimated to be 906 cases per million in the United States and incidence as high as 58 cases per million per year in some European countries [2, 3]. The consequences of SCI encompass motor, sensory and autonomic domains [4]; functional disability, reduced quality of life and high prevalence of affective disorders are common [5]. Chronic neuropathic pain affects up to 75% of people with SCI [5]. The first phase involves direct damage as a result of mechanical trauma. This causes immediate damage and catalyses the second phase of injury driven by aberrant molecular, cellular and biochemical cascades. Secondary injury constitutes damage caused by ischaemia, ionic derangements, excitotoxicity, free radical damage, oedema, inflammation and apoptosis [7, 8]
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