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Brainstem Mechanisms During Placebo Analgesia and Nocebo Hyperalgesia Responses.

Friday, October 29, 2021

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Brainstem mechanisms of pain modulation: a within-subjects 7TfMRI study of placebo analgesia and nocebo hyperalgesic responses

Journal of Neuroscience October 25, 2021, JN-RM-0806-21; DOI: https: //doi.org/10.1523/JNEUROSCI.0806-21.2021

Commentary

Pain perception can be influenced by individual expectations and beliefs, and although the cortical circuits involved in pain modulation have been thoroughly investigated, the brainstem pathways involved in the regulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed.

This study used ultra-high field 7 Tesla functional MRI (fMRI) to precisely resolve the differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants (N= 25; 12 males).

Participants blindly applied a modified thermal stimulus for two consecutive days and were deceptively conditioned to believe that two inert creams labeled "lidocaine" (placebo) and "capsaicin" (nocebo) would act to regulate pain compared to a third "Vaseline" In a subsequent testing phase, fMRI image sets were collected while participants were subjected to identical noxious stimuli at all three cream sites.

Pain intensity ratings were collected and placebo and nocebo responses were determined. Brainstem-specific fMRI analysis revealed changes in the activity of key pain regulatory nuclei, including differential mobilization of the periaqueductal gray (PAG)-rostral medulla ventralis (RVM) pathway in the midbrain when both placebo and nocebo effects were observed, and found that placebo and nocebo responses differentially activated the paraventricular pedunculopontine nucleus, but overlapped in their involvement of the substantia nigra and nucleus accumbens.

These data reveal that the placebo and nocebo effects are generated by different involvement of the PAG-RVM pathway. And the study results suggest that modulating activity at the level of the dorsal horn in concert with other brainstem regions may influence the experience of pain.

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