Health
New study casts doubt on placebo effect and dopamine's role in pain relief
According to a study published Sept. 24, the new findings refute a direct causal role of dopamine in establishing positive expectations of a treatment and placebo analgesia during the experience of therapeutic effects in healthy volunteers.Number Open Access Journals PLOS Biology by Ulrike Bingel of University Hospital Essen in Germany and colleagues.
Dopamine-based reward and learning mechanisms have been suggested to contribute to placebo effects. However, it is still unclear what role the brain messenger molecule dopamine plays in their generation and maintenance. To fill this knowledge gap, Bingel and colleagues investigated the causal role of dopamine in expecting the positive effects of a treatment, as well as the magnitude and duration of its effects on pain. To this end, they applied two opposing drugs that alter dopamine concentrations in the brain, namely the dopamine antagonist sulpiride, in combination with the dopamine precursor L-dopa, and an inactive tablet without drug as a control, to an double-blind, randomized, placebo-controlled trial in 168 healthy volunteers.
The test drug successfully altered dopamine tone during the conditioning procedure. Contrary to the hypothesis, the drug did not modulate the formation of positive expectations for the treatment, and placebo analgesia was tested 1 day later. Placebo analgesia was no longer detectable 8 days after conditioning. Overall, the data provided strong evidence against a direct influence of dopamine on the generation and maintenance of the placebo effect.
The results suggest that although dopamine is not clearly required for the establishment of placebo analgesia, certain dopamine-dependent aspects of reward processing, which are more associated with active action and motivational aspects, may still interact with the experience of pain. Moreover, the results contribute to a more nuanced understanding of the neurobiology underlying placebo analgesia and help characterize the complex interplay between cognition, neurochemistry, and treatment outcome.
According to the authors, further research into the neurochemical mechanisms underlying placebo analgesia remains crucial in the quest to harness these effects for optimal therapeutic outcomes. In particular, future efforts to improve our understanding of the dopaminergic mechanisms regulating therapeutic responses to pain must take into account the undoubtedly complex involvement of dopaminergic neurotransmission in pain and its regulation.
The authors add: “Our research is driven by the motivation to target the underlying mechanisms of the placebo effect to make active medical treatments more effective. Our findings will help redirect the search for new therapeutic targets to achieve this goal.”
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Journal References:
Kunkel, A. Other(2024) Dopamine has no direct causal role in therapeutic expectancy formation or placebo analgesia in humans. PLoS Biology. doi.org/10.1371/journal.pbio.3002772.
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