Thalamus: The ‘promoter’ of endogenous modulation of pain and potential therapeutic target in pathological pain

More recently, the thalamic mediodorsal (MD) and ventromedial (VM) nuclei have been revealed to be functioned as ‘nociceptive discriminator’ in discriminating noxious and innocuous peripheral afferents, and exhibits distinct different descending controls of nociception. Of particularly importance, the function of thalamic nuclei in engaging descending modulation of nociception is ‘silent’ or inactive during the physiological state as well as in condition exposed to insufficient noxious stimulation. Once initiation by sufficient noxious or innocuous C-afferents associated with temporal and spatial summation, the thalamic MD and VM nuclei exhibit salient, different effects: facilitation and inhibition, on noxious mechanically and heat evoked nociception, respectively. Based on series of experimental evidence, we here summarize a novel hypothesis involving thalamic MD and VM nuclei functioned as ‘promoter’ in initiating descending facilitation and inhibition of pain with specific spatiotemporal characteristics. We further hypothesize that clinical remedy in targeting thalamic VM nucleus by enhancing its activities in recruiting inhibition alone or decreasing thalamic MD nucleus induced facilitation may provide promising way in effectively control of pathological pain.