Burkill Sarah, Smith Kelsi A, Stridh Pernilla, Kockum Ingrid, Hillert Jan, Lindahl Hannes, Alfredsson Lars, Olsson Tomas, Piehl Fredrik, Montgomery Scott, Bahmanyar Shahram
Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Solna, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Solna, Sweden.
Front Neurol. 2020 Sep 4;11:993. doi: 10.3389/fneur.2020.00993. eCollection 2020.
Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB103:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB103:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB103:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB103:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB103:02 allele effect is modified by the presence of MS.
小鼠模型已证明，主要组织相容性复合体（MHC）与周围神经损伤时的疼痛样行为有关，然而，在考虑中枢神经系统（CNS）损伤时，尚未发现同样的关联，而中枢神经系统损伤更类似于多发性硬化症（MS）患者所经历的中枢神经系统损伤。先前的研究表明，II类HLA基因的DQB103:02等位基因与腹股沟疝手术患者或腰椎间盘突出症患者的神经性疼痛发展有关。据我们所知，该HLA等位基因是否在疼痛易感性中起作用，此前尚未进行过研究。本研究利用瑞典EIMS、GEMS和IMSE研究中关于DQB103:02等位基因的信息。它还使用了3877名MS患者和4548名匹配的非MS对照者的登记数据，以评估DQB103:02等位基因是否与处方止痛药的使用有关，以及这种基因型的关联是否因MS状态而异。我们的结果显示，MS患者中DQB103:02基因型与止痛药之间无关联，调整后的优势比（OR）为1.02（95%CI 0.85-1.24）。相比之下，在无MS的个体中存在统计学上显著的低强度关联[调整后的OR 1.18（95%CI 1.03-1.35）]，这为HLA对一般人群疼痛易感性的影响提供了支持。此外，纯合性的影响在非MS队列中很明显，但在MS患者中不明显，这表明MS的存在改变了DQB103:02等位基因的作用。
