# Decoding chronic pain: integrating genetics, neuroimaging, and AI for precision management

**Authors:** Bade Uckac, Natalia S. Ogonowski, Luis M. García-Marín, Santiago Diaz-Torres, Scott F. Farrell, Dale R. Nyholt, Miguel E. Rentería

PMC · DOI: 10.3389/fpain.2026.1747942 · Frontiers in Pain Research · 2026-02-06

## TL;DR

This paper reviews how combining genetics, brain imaging, and AI can improve chronic pain treatment by understanding its complex causes and individual differences.

## Contribution

The paper integrates recent findings from genetics, neuroimaging, and AI to advance precision management of chronic pain.

## Key findings

- Chronic pain is linked to genetic, neurobiological, and psychosocial factors with shared pathways in maladaptive neuroplasticity.
- Integrated non-pharmacological approaches show better long-term outcomes than pharmacological treatments.
- Advances in genomics and neuroimaging reveal polygenic and neural circuit overlaps with psychiatric and immune traits.

## Abstract

Chronic pain is increasingly recognised as a standalone medical condition shaped by interacting biological, psychological, and social determinants, affecting nearly one in three adults worldwide. This review synthesises contemporary evidence on the epidemiology, mechanisms, and management of chronic pain, with emphasis on the convergence of genetic, neurobiological, and psychosocial factors. We draw on recent population-based studies, clinical trials, neuroimaging research, and multi-omic genetic analyses to highlight the complexity and heterogeneity of this condition. Chronic pain disproportionately affects older adults, women, and socioeconomically disadvantaged groups, and frequently co-occurs with psychiatric, cardiovascular, and neurodegenerative disorders, reflecting shared pathways of maladaptive neuroplasticity. Although pharmacological therapies often provide modest long-term benefit, integrated psychological, physiotherapeutic, and interventional approaches demonstrate more sustainable improvements in function and quality of life. Advances in genomics and large-scale genome-wide association studies (GWAS) have revealed extensive polygenic overlap with psychiatric and immune traits, while neuroimaging consistently demonstrates alterations within prefrontal, insular, and limbic circuits that shape pain perception and persistence. Despite reliance on subjective symptom reporting, emerging digital phenotyping, wearables, and AI tools offer promising avenues for objective monitoring and personalised treatment. Integrating biological, behavioural, and environmental data will be essential to achieving truly precision-based chronic pain care.

## Full-text entities

- **Genes:** DCC (DCC netrin 1 receptor) [NCBI Gene 1630] {aka CRC18, CRCR1, HGPPS2, IGDCC1, MRMV1, NTN1R1}, DNM1 (dynamin 1) [NCBI Gene 1759] {aka DEE31, DEE31A, DEE31B, DNM, EIEE31}, PCDHA1 (protocadherin alpha 1) [NCBI Gene 56147] {aka PCDH-ALPHA1}, RMDN3 (regulator of microtubule dynamics 3) [NCBI Gene 55177] {aka FAM82A2, FAM82C, RMD-3, RMD3, ptpip51}, PACSIN1 (protein kinase C and casein kinase substrate in neurons 1) [NCBI Gene 29993] {aka SDPI}, CCDC17 (coiled-coil domain containing 17) [NCBI Gene 149483], RHOT2 (ras homolog family member T2) [NCBI Gene 89941] {aka ARHT2, C16orf39, MIRO-2, MIRO2, RASL}, MKRN1 (makorin ring finger protein 1) [NCBI Gene 23608] {aka RNF61}, HECTD3 (HECT domain E3 ubiquitin protein ligase 3) [NCBI Gene 79654], NXPH2 (neurexophilin 2) [NCBI Gene 11249] {aka NPH2}, RAB5B (RAB5B, member RAS oncogene family) [NCBI Gene 5869], PCMT1 (protein-L-isoaspartate (D-aspartate) O-methyltransferase) [NCBI Gene 5110] {aka PIMT}, PPCDC (phosphopantothenoylcysteine decarboxylase) [NCBI Gene 60490] {aka MDS018, PPC-DC, coaC}, WDR90 (WD repeat domain 90) [NCBI Gene 197335] {aka C16orf15, C16orf16, C16orf17, C16orf18, C16orf19, POC16}, DAAM1 (dishevelled associated activator of morphogenesis 1) [NCBI Gene 23002], SLC25A13 (solute carrier family 25 member 13) [NCBI Gene 10165] {aka ARALAR2, CITRIN, CTLN2, NICCD}, UFL1 (UFM1 specific ligase 1) [NCBI Gene 23376] {aka KIAA0776, Maxer, NLBP, RCAD}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, SLC44A2 (solute carrier family 44 member 2 (CTL2 blood group)) [NCBI Gene 57153] {aka CTL2, HNA-3, PP1292}, MAML3 (mastermind like transcriptional coactivator 3) [NCBI Gene 55534] {aka CAGH3, ERDA3, GDN, MAM-2, MAM2, TNRC3}, STAT6 (signal transducer and activator of transcription 6) [NCBI Gene 6778] {aka D12S1644, HIES6, IL-4-STAT, STAT6B, STAT6C}, CCDC32 (coiled-coil domain containing 32) [NCBI Gene 90416] {aka C15orf57, CFNDS}, GABRB2 (gamma-aminobutyric acid type A receptor subunit beta2) [NCBI Gene 2561] {aka DEE92, ICEE2}, COX11 (cytochrome c oxidase copper chaperone COX11) [NCBI Gene 1353] {aka COX11P, MC4DN23}
- **Diseases:** cognitive decline (MESH:D003072), memory impairment (MESH:D008569), mechanical injury (MESH:D041781), restricted movement (MESH:D002313), migraine (MESH:D008881), panic disorder (MESH:D016584), dementia (MESH:D003704), musculoskeletal (MESH:D009140), Neuropathic pain (MESH:D009437), Chronic pain (MESH:D059350), depression (MESH:D003866), cardiac and cerebrovascular (MESH:D002561), toxicity (MESH:D064420), mental health disorders (OMIM:603663), myocardial infarction (MESH:D009203), fibromyalgia (MESH:D005356), Cardiovascular disease (MESH:D002318), back-pain (MESH:D001416), GAD (MESH:D001008), chronic low back pain (MESH:D017116), MDD (MESH:D003865), PTSD (MESH:D013313), stroke (MESH:D020521), visceral pain (MESH:D059265), chronic musculoskeletal pain (MESH:D059352), substance-use disorders (MESH:D019966), psychiatric (MESH:D001523), Alzheimer's disease (MESH:D000544), insomnia (MESH:D007319), SD (MESH:D012735), inflammatory pain (MESH:D010146), cardiovascular, and neurodegenerative conditions (MESH:D019636), inflammation (MESH:D007249), headache (MESH:D006261), pain disorders (MESH:D013001)
- **Chemicals:** coenzyme A synthesis (-), vitamin D (MESH:D014807)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

69 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920503/full.md

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Source: https://tomesphere.com/paper/PMC12920503