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J Pain. 2019 Feb;20(2):201-214. doi: 10.1016/j.jpain.2018.08.011. Epub 2018 Sep 25.

SIGMA-1 Receptor Gene Variants Affect the Somatosensory Phenotype in Neuropathic Pain Patients.

Author information

1
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.
2
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
3
Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
4
Center of Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
5
Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
6
Department of Pain Management, BG Universitätsklinikum Bergmannsheil, Ruhr-University Bochum, Bochum, Germany.
7
Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
8
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. Electronic address: cascorbi@pharmakologie.uni-kiel.de.

Abstract

Pain 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.

KEYWORDS:

Sigma-1 receptor; genetic variants; neuropathic pain; quantitative sensory testing

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