Chronic pain syndromes are characterized by altered neuronal excitability in the pain matrix. The ability to rapidly acquire and store memory of aversive events is one of the basic principles of nervous systems throughout the animal kingdom. These neuroplastic changes take place e. g. in the spinal cord, in thalamic nuclei and cortical and subcortical (limbic) areas integrating pain threshold, intensity and affective components. Chronic inflammation or injury of peripheral nerves evokes the reorganisation of cortical sensory maps. Neurons conveying nociceptive information are controlled by various sets of inhibitory interneurons. The discharge activity of these interneurons counteracts long-term changes in the pain matrix following nociceptor activation, i. e. it prevents the transition of acute pain signaling to chronic pain states. Our most recent research suggests that pain states may be sensitive to novel families of agents and therapeutic measures not predicted by traditional preclinical pain models as well as human pain states. The endogenous cannabinoid system plays a central role in the extinction of aversive memories. We propose that endocannabinoids facilitate extinction of aversive memories via their selective inhibitory effects on GABAergic networks in the amygdala.