{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:22:42Z","timestamp":1780392162552,"version":"3.54.1"},"reference-count":141,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson's UK","doi-asserted-by":"publisher","award":["H-1404"],"award-info":[{"award-number":["H-1404"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Striatal dopamine dysfunction is associated with the altered top-down modulation of pain processing. The dopamine D2-like receptor family is a potential substrate for such effects due to its primary expression in the striatum, but evidence for this is currently lacking. Here, we investigated the effect of pharmacologically manipulating striatal dopamine D2 receptor activity on the anticipation and perception of acute pain stimuli in humans. Participants received visual cues that induced either certain or uncertain anticipation of two pain intensity levels delivered via a CO2 laser. Rating of the pain intensity and unpleasantness was recorded. Brain activity was recorded with EEG and analysed via source localisation to investigate neural activity during the anticipation and receipt of pain. Participants completed the experiment under three conditions, control (Sodium Chloride), D2 receptor agonist (Cabergoline), and D2 receptor antagonist (Amisulpride), in a repeated-measures, triple-crossover, double-blind study. The antagonist reduced an individuals\u2019 ability to distinguish between low and high pain following uncertain anticipation. The EEG source localisation showed that the agonist and antagonist reduced neural activations in specific brain regions associated with the sensory integration of salient stimuli during the anticipation and receipt of pain. During anticipation, the agonist reduced activity in the right mid-temporal region and the right angular gyrus, whilst the antagonist reduced activity within the right postcentral, right mid-temporal, and right inferior parietal regions. In comparison to control, the antagonist reduced activity within the insula during the receipt of pain, a key structure involved in the integration of the sensory and affective aspects of pain. Pain sensitivity and unpleasantness were not changed by D2R modulation. Our results support the notion that D2 receptor neurotransmission has a role in the top-down modulation of pain.<\/jats:p>","DOI":"10.3390\/brainsci12030351","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:35:50Z","timestamp":1646598950000},"page":"351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered Pain Processing Associated with Administration of Dopamine Agonist and Antagonist in Healthy Volunteers"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-3977","authenticated-orcid":false,"given":"Sarah L.","family":"Martin","sequence":"first","affiliation":[{"name":"Department of Psychology, Manchester Metropolitan University, Manchester M15 6GX, UK"},{"name":"The Human Pain Research Group, Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony K. P.","family":"Jones","sequence":"additional","affiliation":[{"name":"The Human Pain Research Group, Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Brown","sequence":"additional","affiliation":[{"name":"The Human Pain Research Group, Division of Neuroscience and Experimental Psychology, The University of Manchester, Manchester M13 9PL, UK"},{"name":"Department of Psychological Sciences, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Kobylecki","sequence":"additional","affiliation":[{"name":"Salford Royal NHS Foundation Trust, Department of Neurology, Manchester Academic Health Science Centre, Salford M6 8HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace A.","family":"Whitaker","sequence":"additional","affiliation":[{"name":"Advanced Center for Electrical and Electronics Engineering, Federico Santa Mar\u00eda Technical University, Valpara\u00edso 1680, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"El-Deredy","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Desarrollo en Ingenier\u00eda en Salud, Universidad de Valpara\u00edso, Valparaiso 1680, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monty A.","family":"Silverdale","sequence":"additional","affiliation":[{"name":"Salford Royal NHS Foundation Trust, Department of Neurology, Manchester Academic Health Science Centre, Salford M6 8HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0304-3959(00)00409-7","article-title":"Role of the dopaminergic system in chronic pain\u2014A fluorodopa-PET study","volume":"90","author":"Rinne","year":"2001","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1111\/j.1460-9568.2007.05623.x","article-title":"Fibromyalgia patients show an abnormal dopamine response to pain","volume":"25","author":"Wood","year":"2007","journal-title":"Eur. 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