Table 2.

Summary of selected studies on the role of VTA in nociception and pain

STUDY	SPECIES	BRAIN REGION	METHOD	MODEL/ TREATMENT	FINDINGS
Ungless et al., 2004	Rat	VTA	Electrophysiology	Foot pinch (15 sec)	Dopamine neurons are specifically excited by reward. A population of non- dopamine neurons is excited by aversive stimuli
Brischoux et al., 2009	Rat	VTA (ventral/ dorsal)	Electrophysiology	Footshock	Inhibition of dorsal VTA dopamine neurons by noxious footshocks Phasic excitation of ventral VTA dopamine neurons by footshocks.
Matsumoto and Hikosaka, 2009	Monkey (Macaca mulatta”)	VTA, Substantia nigra pars compacta	Electrophysiology, monitoring of licking and blinking of the monkeys	Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face)	Large number of dopamine neurons excited by both rewarding/aversive stimuli. Distinct anatomical place of these neurons.
Cohen et al., 2009	Mouse	VTA	Electrophysiology, optogenetics	Odor cues	The first study to assess reward and punishment in optogenetically identified dopamine neurons.
Mileykovskiy and Morales, 2011	Rat	VTA	Electrophysiology and Immunohisto- chemistry	Fear- conditioned rats exposed to stimuli predicting electrical shock	Duration of inhibition of VTA DA neurons encodes negative emotional values of signals predicting aversive events in the environment.
Taylor et al., 2015	Mouse, Rat	VTA (focus on microglia)	In vivo microdialysis, CPP, brain microinjection	Peripheral nerve injury, tail withdrawal assay Inta-Nac cocaine, intra-VTA DAMGO	Peripheral nerve injury-induced activation of microglia within the reward circuit disrupts dopaminergic signaling and reward behavior