Endocannabinoids and neuropathic pain: focus on neuron-glia and endocannabinoid-neurotrophin interactions

Although originally described as a signalling system encompassing the cannabinoid CB1 and CB2 receptors, their endogenous agonists (the endocannabinoids), and metabolic enzymes regulating the levels of such agonists, the endocannabinoid system is now viewed as being more complex, and including metabolically related endocannabinoid-like mediators and their molecular targets as well. The function and dysfunction of this complex signalling system in the molecular and cellular mechanisms of pain transduction and control has been widely studied over the last two decades. In this review article, we describe some of the latest advances in our knowledge on the role of the endocannabinoid system, in its most recent and wider conception, in pain pathways, by focusing on: (1) neuron-glia interactions; and (2) emerging data on endocannabinoid cross-talk with neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor.