• Juliane Sachau, Henrike Bruckmueller, Janne Gierthmühlen, Walter Magerl, Meike Kaehler, Sierk Haenisch, Andreas Binder, Amke Caliebe, Christoph Maier, Rolf-Detlef Treede, Thomas Tölle, Ingolf Cascorbi, and Ralf Baron.
• Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
• J Pain. 2019 Feb 1; 20 (2): 201214201-214.

AbstractPain sensitivity is characterized by interindividual variability, determined by factors including genetic variation of nociceptive receptors and pathways. The sigma-1 receptor (SIGMAR1) is involved in pain modulation especially under pre-sensitized conditions. However, the contribution of SIGMAR1 genetic variants to pain generation and sensitivity is unknown yet. This study aimed to identify effects of 5 SIGMAR1 variants on the somatosensory phenotype of neuropathic pain patients (n = 228) characterized by standardized quantitative sensory testing. Principal component analysis revealed that the SIGMAR1 variants -297G>T (rs10814130) and 5A>C (rs1800866) significantly lowered thermal detection and heat/pressure nociception in particular in neuropathic pain patients with mainly preserved somatosensory function. Compared to wild-type, the variant allele -297T was associated with loss of warm detection (P = .049), lower heat-pain sensitivity (P = .027) and wind-up ratio (P = .023) as well as increased paradoxical heat sensation (P = .020). Likewise for 5A>C the strongest genotype-associated differences observed were reduced peripheral (less heat hyperalgesia; P = .026) and central sensitization (lower mechanical pain sensitivity; P = .026) in variant compared to wild-type carriers. This study indicates lack of association of SIGMAR1 -297G>T and 5A>C genetic variants to susceptibility to develop chronic pain, but significant modulation of somatosensory function in neuropathic pain patients. PERSPECTIVE: This article presents the first study indicating a modulation of somatosensory function in neuropathic pain patients by selected genetic variants in SIGMAR1. As our findings could contribute to the explanation of interindividual differences in drug response they might help to improve the treatment of neuropathic pain.Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.

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