Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity

Abstract

In addition to its involvement in motor control and in encoding reward value, increasing evidence also implicates basal ganglia dopaminergic mechanisms in responses to stress and aversive stimuli. Basal ganglia dopamine (DA) neurotransmission may then respond to environmental events depending on their saliency, orienting the subsequent responses of the organism to both positive and negative stimuli. Here we examined the involvement of DA neurotransmission in the human response to pain, a robust physical and emotional stressor across species. Positron emission tomography with the DA D2 receptor antagonist radiotracer [11C]raclopride detected significant activation of DA release in dorsal and ventral regions of the basal ganglia of healthy volunteers. Activation of nigrostriatal (dorsal nucleus caudate and putamen) DA D2 receptor-mediated neurotransmission was positively associated with individual variations in subjective ratings of sensory and affective qualities of the pain. In contrast, mesolimbic (nucleus accumbens) DA activation, which may impact on both D2 and D3 receptors, was exclusively associated with variations in the emotional responses of the individual during the pain challenge (increases in negative affect and fear ratings). These data demonstrate that basal ganglia dopamine D2 receptor-mediated neurotransmission is involved in responses to pain and that it contributes to individual variations in the pain experience at the levels of physical and emotional elements, albeit with different neuroanatomical substrates.

Figures

Figure 1.

Localization of DA D2 receptor activation during pain in humans. Areas of significant activation of DA D2 neurotransmission during pain, superimposed over an anatomical MRI in coronal views. The left image shows the activation attributable to pain signal (pain − saline control subtraction), localized in the dorsal nucleus caudate and putamen. The magnitude of activation is correlated with sensory and pain affect ratings of the pain. The right image depicts the signal remaining from the activation of DA D2 neurotransmission during pain after pain-specific elements are subtracted: (baseline − pain) − (saline control − pain). The latter is localized in the nucleus accumbens region and associated with the internal negative affective state experienced during pain.

Figure 2.

Correlations between activation of DA D2 neurotransmission during pain and the volunteer's subjective ratings. A, Significant correlation between the pain-specific activation of dorsal caudate DA D2 neurotransmission (percentage reductions in D2 receptor BP from saline control to pain) (SCBP – PBP % Change) and MPQ sensory subscale scores ratings (r = 0.57; p < 0.05). B, Significant correlation between the activation of nucleus accumbens DA D2 neurotransmission during nonspecific elements of pain stress [(baseline − pain) − (saline control − pain subtraction), shown as (BLBP − PBP) − (SCBP − PBP) on the figure] and enhancements in the negative affective state of the volunteers during pain as measured by the PANAS negative affect subscale ratings (Δ PANAS Negative) (r = 0.64; p < 0.01).