In Search of Analgesia: Emerging Poles of GPCRs in Pain

Overview of pain transmission. Nociception begins in the periphery with the activation of nociceptive sensory neurons by noxious stimuli (e.g., heat, acid, or tissue injury). These neurons, which have their cell bodies in the dorsal root ganglia (DRG), synapse on neurons in the spinal cord that send ascending projections to the thalamus, which in turn projects to forebrain regions involved in the subjective experience of pain. Descending inhibitory and excitatory pathways are activated by both ascending input from the spinal cord and descending input from the forebrain and limbic structures, including the amygdala. The major structures modulating descending modulation are found in the brainstem rostral ventral medulla (RVM) and midbrain regions [periaqueductal grey, PAG)].