Dopamine and Pain Sensitivity: Neither Sulpiride nor Acute Phenylalanine and Tyrosine Depletion Have Effects on Thermal Pain Sensations in Healthy Volunteers

Abstract

Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine’s well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats

“…indicating that these two amino acids were intermediate products of the pain response (Becker et al, 2013). Concordant with this study, a lower amount of tyrosine was found in pain patients' excretion (Aghabeigi et al, 1993).…”

“…Previous metabolomics research on regional pain syndrome revealed a pronounced increase in the levels of tyrosine and phenylalanine in the cerebrospinal fluid of patients (Meissner et al, 2014). Interestingly, the acute depletion of phenylalanine and tyrosine was reported to have no effect on nociception, indicating that these two amino acids were intermediate products of the pain response (Becker et al, 2013). Concordant with this study, a lower amount of tyrosine was found in pain patients' excretion (Aghabeigi et al, 1993).…”

Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum

“…Pain activates the dopaminergic system in animal models (Abercrombie et al, 1989;Rougé-Pont et al, 1993;Schmidt et al, 2002;Brischoux et al, 2009) and these data have been corroborated in healthy humans by the observation that experimentally induced increases in pain signal lead to activation of striatal DA D2/D3R neurotransmission as measured using […”

“…Illustrated on the right are plots of average regional D2/D3R activation in the areas showing significant D2/D3R activation in the entire sample (A) and in the area that showed a significant group ϫ condition interaction (B). sensitivity and tolerance have been associated with genetic polymorphisms related to DA system function (Treister et al, 2009;Jääskeläinen et al, 2014), whereas no change was found in these measures after experimental reductions in brain DA (Becker et al, 2013;Tiemann et al, 2014). Nonetheless, specifically regarding striatal DA D2/D3R function, [ 11 C]raclopride PET studies have found significant positive correlations between baseline striatal D2/D3R BP ND and pain sensitivity in HCs (Hagelberg et al, 2002;Scott et al, 2006) and in patients with FM, who showed significant positive correlations between striatal D2/D3R BP ND and measures of both experimental pain sensitivity and widespread tenderness (Wood et al, 2007).…”

Discovery of novel anti-parkinsonian effect of schisantherin A in in vitro and in vivo

“…Interestingly, structurally-similar benzamide and methoxyl groups are present in two antipsychotic drugs, sulpiride and amisulpride (Fig. 1), which are selective antagonists at dopamine D2 and D3 receptors and have been shown to bind to and activate the gamma-hydroxybutyrate receptor (GHB) at doses that are used to treat psychosis via inhibition of dopaminergic neurotransmission [2]. Our findings suggest that unique constituents and positions of different chemical arms, including methylenedioxy, benzoyloxy and methoxyl groups, in the dibenzocyclooctadiene lignan, are probably functionally important to the neuroprotective activity of StA.…”