Painful polyneuropathy is a common neuropathic pain condition with painful diabetic neuropathy being a prominent example. Numerous pathophysiological mechanisms are involved in the generation and maintenance of neuropathic pain. In spite of increasing knowledge about the mechanisms, the treatment of neuropathic pain is still unsatisfactory. The effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on pain in polyneuropathy was tested in an earlier randomized, placebo-controlled, double- blinded cross-over trial including 41 patients who were treated with 20 mg escitalopram and placebo. The clinical study showed a moderate, good or complete pain relief for escitalopram in 11 patients ("responders") but at only a slight or no relief in 30 patients ("non-responders"). The difference in response to escitalopram may be caused by genetic differences between the responders and the non-responders, which led to a pharmacogenomic study investigating genetic differences between the two groups for functional variants in genes involved in the signaling pathway for serotonin. We tested the serotonin receptor subunits 5-HTR2C G68C (rs6318) and 5-HTR2A C1354T (rs6314) both giving rise to amino acid changes. We furthermore tested a missense variant in the gene coding for P-glycoprotein, ABCB1 G2677T (rs2032582) and a promoter polymorphism (5-HTTLPR) in the serotonin transporter gene. We were not able to find any statistical significant association between the tested genetic polymorphisms and effect of escitalopram when dichotomizing the patients into responders and non-responders. Using quantitative assessment of pain might add more information to the association studies.
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World congress of basic and clinical pharmacology, 2010