Costa, A. E. Trovato, F. Comelli, G. Giagnoni, M. Colleoni
- CBD reversed hyperalgesia after 7 days of oral treatment in 2 models of persistent pain in rats
- Repeated administration of CBD oil abolished/reduced the levels of molecules implicated in the pathogenesis of many inflammatory disorders and pain installation
- The study put into evidence the anti-hyperalgesic potency of CBD, while being a non-toxic and non-psychotropic agent
OBJECTIVES & HYPOTHESIS → The main aim of this study was to determine the therapeutic potential and efficacy of prolonged treatment with cannabidiol on pain in models of neuropathy and chronic inflammation. This work also examined whether cannabidiol inhibited the production of nociceptive and inflammatory mediators involved in chronic painful states.
METHODS → Blinded, randomized controlled trial with artificial establishment of two persistent-pain models. The chronic neuropathic pain model was induced by chronic constriction injury of the sciatic nerve in the right hind paw and the inflammatory model by injection of Mycobacterium tuberculosis. Both models had a control group. The control group was given oral doses of vehicle (pharmacological neutral) while the treatment group (both neuropathic and inflamed rats) recieved oral cannabidiol or vehicle. Doses for neuropathic rats were of 2.5, 5, 10 and 20 mg/kg while for inflamed rats were only of 20mg/kg. The mechanical and thermal hyperalgesia were measured, as well as the levels of mediators involved in pain physiology.
RESULTS → Before surgery or injection, rats withdrew their left and right hind paws from radiant heat with a latency of about 10s and sustained a mechanical force of about 100g. Seven days after sciatic nerve ligature or adjuvant injection, there was a decrease of about 50% in both thermal and mechanical withdrawal latency. Repeated administration of cannabidiol attenuated both thermal and mechanical hyperalgesia of neuropathic rats in a dose-dependent manner; the highest dose abolished hyperalgesia and induced full pain relief in inflamed rats.
Paw withdrawal latency (PWL) is a measure of pain sensitivity. On day 0, all groups had a PWL of 10s. On day 7, inflammation was induced, which resulted in a drop of almost 50% in PWL in the inflammatory chronic pain-groups. On day 14, the inflamed subjects treated with vehicle didn’t improve their PWL values, while the subjects treated with CBD almost totally regained their original pain sensitivity. Values on PWL of the healthy group did not change for the 14 days.
The CBD oil treatment also induced a slight reduction of PGE2 production; suppressed the lipid peroxide overproduction in paw tissue; brought the NO content down to a non-pathological level; and inhibited the stimulation of the glutathione system. All these molecules and signaling pathways were increased in both neuropathic and inflammatory models prior to CBD administration and are implicated in pain physiology.