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Somatotopic organization of brainstem analgesic circuitry

Crawford, Lewis1; Tinoco Mendoza, Fernando1; Robertson, Rebecca1; Meylakh, Noemi1; Macey, Paul2; Bannister, Kirsty3; Wager, Tor4; Macefield, Vaughan5; Keay, Kevin1; Henderson, Luke1

Published Aug 11, 2025 on Dryad. https://doi.org/10.5061/dryad.np5hqc064

Data files

Abstract

Rationale: By conducting a placebo analgesia conditioning paradigm using a falsely labelled and described cream, 93 pain-free participants believed this cream could reduce the intensity of painful heat applied to either their face, arm, or leg. In reality, this “lidocaine” cream was a placebo, and the temperature of a thermode surreptitiously lowered whenever placed onto this cream relative to a control Vaseline cream site. During collection of images of brainstem activity using a 7-Tesla Magnetic Resonance Imaging scanner, both the placebo and control cream sites received identical temperatures, with a decrease in perceived pain intensity during the placebo cream site stimulation being a placebo analgesia response. We analysed activity changes in the PAG and an area that the PAG contacts to inhibit pain, the rostral ventromedial medulla (RVM), during analgesia responses on the face, arm, and leg. Further, using the hidden application of a third cream to a separate body site, we explored whether analgesia was restricted to the area of stimulation or whether it was more widespread.

Results: Our findings show that analgesia evoked on the face, arm, and leg changes activity in a somatotopically organized fashion, i.e. face analgesia is towards the rostral (top) of the PAG and RVM, arm and leg analgesia represented more caudally (lower). These somatotopically organized analgesic responses occurred on opposite sides of the PAG but at the same locations as pain activity changes, and the analgesia was restricted to the site where conditioning was applied.