Systematic review of the impact of cannabinoids on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury

Abstract

Study design Systematic review. Objectives To 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. Methods A 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. Results The 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. Conclusion Modulation 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.

Meeting the Shared Goals of a Student-Selected Component: Pilot Evaluation of a Collaborative Systematic Review

“…As of the time of writing, 1 of the SRs has been published and the other is being prepared for submission [ 16 ].…”

“…Both SRs were in due reference to the priorities of patients with DCM, expressed through forums including Myelopathy.org, an international myelopathy charity, and the Research Objectives and Common Data Elements for DCM process, an international consensus process to define the research priorities for DCM [13][14][15]. The topics of the reviews were (1) the impact of phosphodiesterase 3 and 4 inhibition on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury and (2) the role of cannabinoids on modulating neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury [16]. Both reviews were registered on PROSPERO (University of York, United Kingdom; CRD42019150639 and CRD42019149671, respectively).…”

“…Both reviews were registered on PROSPERO (University of York, United Kingdom; CRD42019150639 and CRD42019149671, respectively). Search strategy and protocol development was led by the 2 lead students, with reference to previous SRs conducted by our group, followed by review, discussion, and feedback from postgraduate researchers [15][16][17][18][19][20][21].…”

Lentiviral-Induced Spinal Cord Gliomas in Rat Model

“…Each rat was placed in an enclosure measuring 1m by 0.5m and observed for 5–10 min for any motor deficits listed on the 21-point BBB scoring scale, where 21 is normal and 0 represents no movement in any of the three leg joints [ 22 ]. Tarlov scoring is a more general gauge of motor function, measuring the degree of paralysis in the hindlimbs within scores of 0–4 [ 53 ]. Tarlov scoring was determined in the same exam period based on the following descriptions: (0) no voluntary movement, (1) perceptible movement at the joint, (2) good joint mobility but the inability to stand, (3) ability to stand and walk, and (4) complete recovery [ 54 ].…”

Endocannabinoid signaling in microglia

“…Some studies showed an elevation of CBRs in the spinal cord, especially the CB2R, after acute neuropathological conditions such as SCI, neuropathic pain and movement disorder, and amelioration of pain hypersensitivity upon treatment with cannabinoid compounds (Bhatti et al, 2021; Duffy et al, 2021). On the other hand, it was reported that spinal TRPV1 participates in neuropathic pain state maintenance and exacerbation through the extra‐release of glutamate (Choi et al, 2016; Uta et al, 2019).…”