What Are the Interactions Between the Midbrain Dopamine System in Pain?

There is both experimental and indirect clinical evidence that dopaminergic neurons in the ventral tegmental area (VTA) respond to acute painful stimuli and are involved in the perception, modulation, and behavioral response of chronic pain (reviewed in references 1 and 2). However, the precise role of this system remains poorly understood given the functional heterogeneity of these neurons, including their different targets and their differential response to acute painful stimuli, plastic changes in response to nerve injury associated with neuropathic pain, and effects on different forebrain areas involved in emotion, reward processing, and motivation.(1-4) Most of the recent insights into the role of dopaminergic VTA neurons in mechanisms of pain result from elegant studies in rodents combining optogenetics, chemogenetics, calcium imaging, viral tracing, single-cell recording, and behavioral measures, both in response to acute noxious stimulation and in experimental models of chronic pain, typically that induced by peripheral nerve injury.(5-11) Whereas these results may not be easily extrapolated to clinical situations in humans, they provide evidence that chronic pain is associated with dysfunction of the midbrain dopaminergic system and its targets. This has been demonstrated indirectly using neuroimaging modalities in humans(12-14) and is clinically relevant given the function of this system at the interface between pain and reward, motivation, and drug-seeking behavior.(4,15,16) This subject has been the topic of comprehensive reviews(1,2,15,16) and other concepts are briefly discussed here.

Automated summary

The dopaminergic neurons in the ventral tegmental area (VTA) play a role in the perception and modulation of chronic pain. Recent studies in rodents using various techniques have provided insights into the dysfunction of the midbrain dopaminergic system in chronic pain. This has clinical relevance and has been indirectly demonstrated in humans using neuroimaging techniques.