Genetic factors (WP5)

One component of neuropathic pain is genetic. Knowing which genes contribute to what types of neuropathic pain can help identify the mechanisms at work behind the disease, develop better drugs, and assess an individual's risk of developing neuropathic pain. This research theme uses different types of genetic analysis to explore these questions.

Neuropathic pain has an estimated heritability of 37%, although the specific genetic variants involved are still poorly understood. We reviewed all genetic variants known to be associated with neuropathic pain and identified "candidate" genes involved in a range of pathways including immune responses, neurotransmission, ion channels, and metabolism. Monogenic pain disorders (such as congenital insensitivity to pain) and extreme pain disorders (such as erythromelalgia) are rare but have highlighted the role of ion channels in human pain and provided novel targets for pain therapy.

Testing known candidate genes and discovering new genetic variants associated with neuropathic pain

We are using existing resources, in particular the new pain phenotype data in UK Biobank, that include rich phenotyping for neuropathy, co-morbidities (anxiety, depression), and quality of life. Neuropathic pain phenotyping of SHARE and follow-up data in GoDARTs will provide a focus on painful diabetic neuropathy, one of the most common causes of neuropathic pain in the community. With this resource, we will perform the largest genome-wide association studies (GWAS) of neuropathic pain to date. We will work with patient partners to decide the outcomes that are most relevant to them.

Describing rare genetic variants with high impact on specific neuropathic pain conditions

We will combine whole exome sequencing (WES) with TWIST technology to provide whole exome coverage on a panel of 45 pain genes. This will enable us to study the role of rare variants in known candidate genes such as SCN9a but will also be informative across the exome. There will be close collaboration with Work Package 6 to optimise the choice of variants for functional analysis.

Studying the shared genetic architecture of neuropathic pain with other pain disorders and trans-ethnic comparison

We have established collaborations to validate and replicate the genetic findings from PAINSTORM. These includes the GeNEUP study (Norway) and IDNC (Denmark). We also have potential collaborations via the University of Dundee to compare our results with those from a study of the genetics of painful diabetic neuropathy in an Indian cohort. The collaborations within the Advanced Pain Discovery Platform will facilitate the study of the shared genetic architecture of neuropathic pain and other pain disorders, such as visceral pain with the ADVANTAGE consortium and sciatica with the FORECAST project.


The epidemiology of neuropathic pain in UK Biobank

Using the improved pain data available in UK Biobank, we verified that previously known factors associated with neuropathic pain in population studies could be replicated in UK Biobank. We confirmed that using the DN4 questionnaire (Douleur Neuropathique en 4 Questions / Neuropathic Pain in 4 Questions) to define neuropathic pain gives results consistent with previous research. We found, amongst other things, that neuropathic pain was:

  • Associated with worse health-related quality of life, being female, and being younger compared to the control group with no chronic pain;
  • Associated with pain in the limbs, greater pain intensity, higher body mass index, and being male compared to the control group with chronic, non-neuropathic pain;
  • Associated with diabetes and neuropathy, but also other pains (pelvic, postsurgical, and migraine) and musculoskeletal disorders (rheumatoid arthritis, osteoarthritis, and fibromyalgia).

Read the full paper here:
Georgios Baskozos, Harry Hébert, et al. Epidemiology of neuropathic pain: an analysis of prevalence and associated factors in UK Biobank. PAIN Reports 8(2):p e1066, March 2023. Open Access logo which is a illustration of an open padlock

  1. This paper reviews genetic factors found to be associated with neuropathic pain: Systematic review and meta-analysis of genetic risk factors for neuropathic pain Open Access logo which is a illustration of an open padlock