Abstract : New research reveals that dopamine is not directly responsible for the formation of placebo analgesia, contrary to previous belief. In a study of 168 participants, altering dopamine levels did not affect positive treatment expectations or pain relief.
The results suggest that dopamine may play a more subtle role in reward processing, rather than directly influencing placebo effects. This finding advances our understanding of the brain’s response to placebo treatments. Future research will focus on other mechanisms that may enhance treatment outcomes.
Key Facts :
- Dopamine is not essential for generating placebo-induced pain relief.
- Altering dopamine levels had no effect on positive treatment expectations.
- The results suggest that the role of dopamine is more related to reward processing.
Source : PLOS
New findings argue against a direct causal role for dopamine during the experience of a treatment effect on positive expectancy formation and placebo analgesia in healthy volunteers, according to a study published September 24 in the open-access journal PLOS Biology by Ulrike Bingel of the University Hospital of Essen in Germany and colleagues.
Dopamine-based reward and learning mechanisms have been suggested as contributors to placebo effects. However, the exact role of dopamine in generating and maintaining these effects remains unclear.
The results indicate that, although dopamine is not necessary to establish placebo analgesia, certain dopamine-dependent dimensions, more linked to active action and motivational aspects, may interact with the pain experience.
To fill this knowledge gap, Bingel and colleagues examined the causal role of dopamine in the expectation of positive treatment effects, as well as the magnitude and duration of its effects on pain.
To do this, they used an established paradigm of placebo pain relief, combined with two opposing drugs to alter dopamine levels in the brain: the dopamine antagonist sulpiride, the dopamine precursor L-dopa, and an inactive pill as a control. The study was an experimental, double-blind, randomized, placebo-controlled trial involving 168 healthy volunteers.
The study medication successfully altered dopaminergic tone during the conditioning procedure. However, contrary to hypothesis, the medication did not modulate the formation of positive treatment expectancy or placebo analgesia tested one day later.
Placebo analgesia was not detected on day 8 after conditioning. Overall, the data provided strong evidence against a direct influence of dopamine in the generation and maintenance of placebo effects.
The results suggest that, although dopamine is not necessary to establish placebo analgesia, certain dopamine-dependent dimensions, more linked to active agency and motivational aspects, may interact with the pain experience.
Furthermore, the results contribute to a more detailed understanding of the neurobiology underlying placebo analgesia, which helps characterize the complex interplay between cognition, neurochemistry, and treatment outcomes.
According to the authors, further exploration of the neurochemical mechanisms that underlie placebo analgesia is essential in the quest to optimize these effects for more effective treatment outcomes.
In particular, future efforts to advance the understanding of dopaminergic mechanisms to modulate the response to pain treatment must consider the arguably complex involvement of dopaminergic neurotransmission in pain and its modulation.
The authors add: “Our research is motivated by the desire to target the mechanisms underlying placebo effects to make active medical treatments more effective. The results of our study help redirect the search for new treatment targets to achieve this goal.”
