Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Department of Surgical Sciences, Anaesthesiology/Pain research, Uppsala University, Uppsala, Sweden Department of Anaesthesiology, University of Tammerfors, Tampere, Finland Department of Clinical Science, Intervention and Technology (Surgery), Karolinska Institutet, Huddinge, Sweden National Institute of Occupational Health, Oslo, Norway Department of Molecular Biosciences, University of Oslo, Norway Department of Biomedical Laboratory Science, Faculty of Health and Society, Malmö University/Labmedicine Skåne, Clinical Chemistry, Malmö, Sweden Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden Department of Anesthesiology and Intensive Care, Haukeland University Hospital, Bergen, Norway Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Ullevaal, Norway.
Pain. 2013 Mar;154(3):427-433. doi: 10.1016/j.pain.2012.12.003. Epub 2012 Dec 13.
Neuropathic pain conditions are common after nerve injuries and are suggested to be regulated in part by genetic factors. We have previously demonstrated a strong genetic influence of the rat major histocompatibility complex on development of neuropathic pain behavior after peripheral nerve injury. In order to study if the corresponding human leukocyte antigen complex (HLA) also influences susceptibility to pain, we performed an association study in patients that had undergone surgery for inguinal hernia (n=189). One group had developed a chronic pain state following the surgical procedure, while the control group had undergone the same type of operation, without any persistent pain. HLA DRB1genotyping revealed a significantly increased proportion of patients in the pain group carrying DRB104 compared to patients in the pain-free group. Additional typing of the DQB1 gene further strengthened the association; carriers of the DQB103:02 allele together with DRB104 displayed an increased risk of postsurgery pain with an odds risk of 3.16 (1.61-6.22) compared to noncarriers. This finding was subsequently replicated in the clinical material of patients with lumbar disc herniation (n=258), where carriers of the DQB103:02 allele displayed a slower recovery and increased pain. In conclusion, we here for the first time demonstrate that there is an HLA-dependent risk of developing pain after surgery or lumbar disc herniation; mediated by the DRB104 - DQB103:02 haplotype. Further experimental and clinical studies are needed to fine-map the HLA effect and to address underlying mechanisms.
神经病理性疼痛是神经损伤后的常见病症，部分由遗传因素调控。我们之前的研究表明，大鼠主要组织相容性复合体对周围神经损伤后神经病理性疼痛行为的发展有很强的遗传影响。为了研究人类白细胞抗原复合体（HLA）是否也会影响疼痛易感性，我们对接受腹股沟疝手术的患者（n=189）进行了一项关联研究。一组患者在手术后出现慢性疼痛状态，而对照组患者接受了相同类型的手术，但没有持续疼痛。HLA-DRB1 基因分型显示，疼痛组携带 DRB104 的患者比例明显高于无疼痛组。对 DQB1 基因的进一步分型进一步加强了这种关联；携带 DQB103:02 等位基因和 DRB104 的患者与非携带者相比，手术后疼痛的风险增加，优势比为 3.16（1.61-6.22）。这一发现随后在腰椎间盘突出症患者的临床资料中得到了验证（n=258），其中携带 DQB103:02 等位基因的患者恢复较慢，疼痛增加。总之，我们首次证明 HLA 依赖性与手术后或腰椎间盘突出症后疼痛的发展风险有关；由 DRB104-DQB103:02 单体型介导。需要进一步的实验和临床研究来精细定位 HLA 效应并探讨潜在机制。
