Abstract
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 DQB1*03:02 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 DQB1*03:02 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 DQB1*03:02 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 DQB1*03:02 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 DQB1*03:02 allele effect is modified by the presence of MS.
Highlights
Multiple sclerosis (MS) is an immune mediated, inflammatory disease, with selective targeting of the central nervous system (CNS)
In view of previous human data on the human leukocyte antigen (HLA) association with peripheral neuropathic pain, in this study we focused on the question of whether carriers of the allele DQB1∗03:02 had an increased risk of pain and if such an effect would be different in MS patients and those without MS
Both general pain and neuropathic pain can be identified using prescriptions of pain medication as a proxy, which can identify pain with a reasonable degree of accuracy, [1] and we examined these categories of pain using the same definitions in those with and without MS
Summary
Multiple sclerosis (MS) is an immune mediated, inflammatory disease, with selective targeting of the central nervous system (CNS). The neuropathic pain in MS likely stems from the disease inherent lesions in the CNS [2] It is not clear why some patients develop neuropathic pain and some do not. It may be a stochastic phenomenon depending on where in the nervous system a person has inflammatory lesions. It is valid to study this in MS in view of experimental data on non-specific damage to the CNS and peripheral nervous system, showing both MHC and non-MHC genetic influences on the development of pain [6,7,8]. In humans, regarding damage to the peripheral nervous system, the DQB1∗03:02 allele of HLA class II has been associated with development of neuropathic pain in persons that have undergone inguinal hernia surgery or with lumbar spinal disk herniation [9]. There are drugs used for neuropathic pain, including pregabalin and gabapentin, which our previous study used to identify instances of neuropathic pain [1]
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