Tramadol effects on brain activity during cognitive and emotional empathy for pain: a randomized controlled study

Pain is perceived not only by personal experience, but also vicariously. Pain empathy is the ability to share and understand other's intentions and emotions in their painful conditions, which can be divided into cognitive and emotional empathy. It remains unclear how centrally acting analgesics would modulate brain activity related to pain empathy, and which component of pain empathy would be altered by analgesics. In this study, we examined the effects of the analgesic tramadol on the brain activity for pain empathy in healthy adults. We used two tasks to assess brain activity for pain empathy. In experiment 1, we used a well-established picture-based pain empathy task involving passive observation of other's pain. In experiment 2, we developed a novel pain empathy task to assess brain activity during cognitive and emotional empathy for pain separately in a single task. We conducted a double-blind, placebo-controlled within-subject cross-over study with functional magnetic resonance imaging for 33 participants in experiment 1 and 31 participants in experiment 2, respectively. In experiment 1, we found that tramadol decreased activation in the supramarginal gyrus (SMG) during observation of other's pain compared to placebo. SMG activation correlated negatively with the thermal pain threshold. In experiment 2, we found that tramadol decreased activation in angular gyrus in cognitive empathy for pain compared to placebo, but didn't change brain activity in emotional empathy for pain. PERSPECTIVE: Centrally acting analgesics such as tramadol may have not only analgesic effects on self-experienced pain, but also on the complex neural processing of pain empathy. DATA AVAILABILITY: Data are available on reasonable request from the corresponding author.