The Role of the Brain’s Reward System in Expectation of Pain

Post by Kasey Hemington

What's the science?

Pain is a subjective experience that can be modulated by many factors, including its anticipation. The brain’s reward system works by detecting the difference between events that we experience and their prior anticipation and is known to be involved in how we perceive pain. The ventral tegmental area (VTA) projects to the rostral anterior cingulate cortex and nucleus accumbens via the mesocorticolimbic pathways and is a key part of the brain’s reward system. How these pathways might play a role in encoding our expectations of pain is not clear. This week in The Journal of Neuroscience, Tu and colleagues studied the structure and function of the mesocorticolimbic pathways using magnetic resonance imaging (MRI) during a task in which humans anticipated a painful experience.

How did they do it?

Twenty-nine young adults (14 females) participated in the experiment, which involved a calibration phase, a conditioning phase, and a test phase. During the calibration phase, electrical stimulation was delivered to the forearm to identify the level at which each individual reported low pain (2/10), moderate pain (4/10) and high pain (6/10). In the conditioning phase, participants saw a + sign or – sign on a screen, which they were told was ‘associated with a painful stimulus’. Fifteen seconds after seeing the + sign or – sign, the high pain or low pain level of electrical stimulation respectively was delivered. In other words, the participants were conditioned to associate the + with more pain and the – with less pain. During the test phase, participants again viewed the + or – sign prior to experiencing the painful stimuli, however, unbeknownst to participants, the same moderately painful stimuli were delivered after every image shown, in order to test conditioning effects. Participants were also shown an ‘o’ symbol on some trials during the test phase that they did not see during the conditioning phase, which could be assumed to be ‘neutral’. After receiving the painful stimulus, participants rated the pain.

During the test phase, functional MRI (fMRI) scanning was performed and the connectivity of the VTA with other brain regions was analyzed while participants viewed the images and anticipated the painful stimuli. The authors studied a ‘positive expectancy effect’, the difference between pain perception in response to the – sign versus the o sign, and a ‘negative expectancy effect’, the difference between pain perception in response to the + sign versus the o sign. Structural MRI data (assessing the brain’s grey matter volume) was also collected.

What did they find?

On average, pain following the -, o and + cues was rated as 2.69/10, 3.32/10 and 4.10/10 respectively during the test phase, indicating that the conditioning phase was effective. The VTA was more tightly functionally connected with the rostral anterior cingulate cortex and the nucleus accumbens during – cues compared to o cues, and less tightly connected during + cues compared to o cues. There was also a negative relationship across trials between perceived pain intensity and VTA connectivity with the aforementioned brain regions. In statistical mediation analyses, VTA – nucleus accumbens functional connectivity and VTA – rostral anterior cingulate cortex functional connectivity were found to mediate the effect of expectancy (due to a cue) on pain perception. For example, if someone had an expectation of high pain and low VTA – nucleus accumbens functional connectivity, this might result in them reporting higher pain perception than they otherwise might have.

When the authors compared VTA functional connectivity across subjects, they found that it did not predict pain responses. However, when they analyzed the structural MRI data, they found that grey matter volumes of the VTA, rostral anterior cingulate cortex, and nucleus accumbens predicted the positive expectancy effect - individuals with larger volumes in these areas were likely to experience a larger effect. Grey matter volume of the rostral anterior cingulate cortex predicted a larger negative expectancy effect.

What's the impact?

This study demonstrates that the function and structure of the VTA and mesocorticolimbic pathways are related to one’s anticipation of a painful experience. These results emphasize the role of the brain’s reward system in shaping how expectancy of pain can alter the way we feel pain.

Tu et al. Mesocorticolimbic pathways encode cue-based expectancy effects on pain. Journal of Neuroscience (2019). Access the original scientific publication here.