Increased risk of persistent neuropathic pain pain after traumatic nerve injury and surgery for carriers of an HLA-haplotype

Presentatörer: Adriana Miclescu,¹ Clara Rönngren, ¹ Mats Bengtsson, ² Anders Hedin ^{2 ,} Torsten Gordh, ¹

¹Dept. of Surgical Sciences, Uppsala University, ²Dept. of Immunology, Genetics and Pathology, Uppsala University, Sweden

Background: It is not known why some patients develop persistent pain after surgery (PPS) while others do not. Among multiple risk factors for the development of PPS, a neuropathic mechanism due to iatrogenic nerve lesion has been proposed as the major cause of PPS.

Aim: As there is some evidence that the Human Leukocyte Antigen (HLA) system plays a role in PPS, this study aimed to identify the genetic risk factors specifically among HLA-loci associated with persistent pain after trauma and surgery of the nerve injuries in the upper extremities.

Method: Blood samples were taken to investigate the contribution of HLA alleles (i.e. HLA-A, HLA-B, HLA-DRB1, HLA-DQB1, HLA-DPB1) in a group of subjects with persistent neuropathic pain (n=70) and a group of patients with neuropathy without pain (n=61). All subjects had intraoperatively verified nerve damage in the upper extremity. They underwent bedside clinical neurological examination to identify the neuropathic pain component according to the present grading system of neuropathic pain. Statistical analyses on the allele, haplotype were carried out using the BIGDAWG package.

Results: We found that the HLA-haplotype A*02:01-B*15:01-C*03:04-DRB1*04:01-DQB1*03:02, was associated with an increased risk of developing persistent neuropathic pain in the upper extremity (OR=9.31 [95% CI 1.28-406.45], p<0.05). No significant associations were found on an allele level when correcting for multiple testing.

Slutsats: An association between HLA and the risk of developing persistent neuropathic pain after trauma was found in the carriers of the A*02:01-B*15:01-C*03:04-DRB1*04:01-DQB1*03:02 haplotype who displayed an increased risk of chronic neuropathic pain and increased risk of PPS. Further studies are needed to investigate if this association is on a haplotypic level or if certain alleles may be causing the association.