Étant donné que l'utilisation des cannabinoïdes dans un but thérapeutique est en pleine expansion, notre laboratoire a voulu vérifier, à l'aide de deux études cliniques fondamentales chez des sujets sains, le potentiel analgésique d'un cannabinoïde synthétique, le nabilone, lors de différents tests de douleur. Ces tests incluent l'utilisation d'une thermode (plaque chauffante) utilisée sur la peau à des températures supérieures au seuil de la douleur ainsi que l'utilisation du test du réflexe RIII vu par électromyogramme (EMG) et potentiels évoqués vus par électroencéphalogrammes (EEG) réalisé à l'aide de stimulations électriques du nerf sural. L'effet analgésique du nabilone était vérifié à l'aide de ces mesures électrophysiologiques de même que par l'utilisation de méthodes psychophysiques de mesure de perception de la douleur des participants utilisant une échelle analogue visuelle de la douleur allant de 0 à 100. Le potentiel synergistique du nabilone suite à l'activation d'un mécanisme de contrôle de la douleur appelé contrôle inhibiteur diffus nociceptif (CIDN) a aussi été vérifié. Ces tests furent effectués en double aveugle avec un placébo et des doses de 0 mg, 0,5 mg et 1 mg de nabilone. Malgré une tendance positive, nous n'avons pas réussi à voir un effet analgésique concret du nabilone 0 mg, 0,5 mg et 1 mg plus fort que l'effet placébo aussi bien dans les tests de thermode que de RIII. Le nabilone n'a pas su non plus, sur la population totale, créer d'effet synergistique avec l'effet du CIDN. Par contre, suite à des analyses statistiques plus poussées, nous avons pu voir que le nabilone avait, chez les femmes, un effet antihyperalgésique suite à l'activation du CIDN. Des effets très différents ont pu aussi être vus entre la réponse des femmes et des hommes suite au test du RIII quant à son effet spinal et supraspinal.

Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, resulting in significant challenges in its management. In addition to its complex pathophysiology, the clinical management of MS-induced NPP is further complicated by the lack of clinical therapeutics trials specific to this population. The primary aim of the work underlying this thesis was to contribute to the evidence-based management of individuals with MS-induced NPP through the completion of two clinical therapeutics trials in this population. A secondary aim was to describe pain variability in this patient population through the development and validation of a pain variability algorithm tool. Resulting from this work, we demonstrated that nabilone – a synthetic oral cannabinoid – represents an effective, well-tolerated and novel treatment for MS-induced NPP. Additionally, we show that the SSRI paroxetine was poorly tolerated in our patient population, with a correspondingly high attrition rate. As a result, we were unable to determine any treatment effect in this trial due to insufficient recruitment due to drop-out. Lastly, we were able to define and describe pain instability in this cohort, noting that approximately 30% of individuals with MS-induced NPP experiencing highly variable daily pain. The results of these projects provide novel information for this patient population. Patients currently living with the daily burden of MS-induced NPP would benefit from additional trials ensuing from this, and other, research in order to initiate a momentum for much-needed clinical research in this complicated patient cohort.

Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, resulting in significant challenges in its management. In addition to its complex pathophysiology, the clinical management of MS-induced NPP is further complicated by the lack of clinical therapeutics trials specific to this population. The primary aim of the work underlying this thesis was to contribute to the evidence-based management of individuals with MS-induced NPP through the completion of two clinical therapeutics trials in this population. A secondary aim was to describe pain variability in this patient population through the development and validation of a pain variability algorithm tool. Resulting from this work, we demonstrated that nabilone – a synthetic oral cannabinoid – represents an effective, well-tolerated and novel treatment for MS-induced NPP. Additionally, we show that the SSRI paroxetine was poorly tolerated in our patient population, with a correspondingly high attrition rate. As a result, we were unable to determine any treatment effect in this trial due to insufficient recruitment due to drop-out. Lastly, we were able to define and describe pain instability in this cohort, noting that approximately 30% of individuals with MS-induced NPP experiencing highly variable daily pain. The results of these projects provide novel information for this patient population. Patients currently living with the daily burden of MS-induced NPP would benefit from additional trials ensuing from this, and other, research in order to initiate a momentum for much-needed clinical research in this complicated patient cohort.