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Dopaminergic neurotransmission and genetic variation in chronification of post-surgical pain
Roel R.I. van Reij, Elbert A.J. Joosten, Nynke J. van den Hoogen British Journal of Anaesthesia Volume 123, Issue 6, Pages (December 2019) DOI: /j.bja Copyright © 2019 British Journal of Anaesthesia Terms and Conditions
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Fig 1 Genetic variations and dopaminergic neuromodulation in spinal cord nociceptive network. This figure illustrates DA neurotransmission between primary afferents, descending neurones and the second-order pain transmission neurones in the spinal dorsal horn. SNPs in DA neurotransmission are shown as rs numbers. Rs841 is located in GCH1 and decreases expression of GCH1, affecting the production of dopamine. Rs6277 is located in DRD2 (D2 receptor) and decreases the stability of the mRNA, thereby decreasing the expression of the D2 receptor. Rs4680 and rs are both located in COMT, and both decrease the enzymatic activity of COMT. Each of these variations are located at key points in the dopaminergic neurotransmission and influence the effect of dopamine on nociception by altering the signalling cascade. 3MT, 3-methoxytyramine; AC, adenylyl cyclase; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; AADC, aromatic l-amino acid decarboxylase; cAMP, cyclic adenosine monophosphate; BH4, tetrahydrobiopterin; COMT, catechol-O-methyltransferase; D1, dopamine 1-like receptor; D2, dopamine 2-like receptor; DARPP-32, dopamine- and cAMP-regulated neuronal phosphoprotein; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; GCH1, GTP cyclohydrolase 1; GTP, guanosine triphosphate; HVA, homovanillic acid; K+, potassium channel; l-DOPA, levodopa; MAO, monoamine oxidase; Na+, sodium channel; NET, norepinephrine transporter; NMDA, N-methyl-d-aspartic acid; PKA, protein kinase A; PP1, protein phosphatase 1; rs#, reference snp number; SNP, single nucleotide polymorphism; TH, tyrosine hydroxylase; VMAT2, vesicular monoamine transporter 2. Red circles represent glutamate-containing synaptic vesicles, and yellow circles represent DA-containing synaptic vesicles. British Journal of Anaesthesia , DOI: ( /j.bja ) Copyright © 2019 British Journal of Anaesthesia Terms and Conditions
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