Active Mental Health Brain & Nervous System

Hyperalgesic Priming in Chronic Widespread Pain: Role of the Stress Axes

Funder Wellcome Charity-funded
Recipient organisation University of Liverpool
Funding £1.7M
Period Mar 2026 — Feb 2034

In plain English

AI plain-English summary

Chronic pain leaves millions in the UK trapped in a cycle of suffering that costs the economy over £10 billion each year, yet doctors still cannot predict who will develop it or why. The problem is that stress and early-life adversity—common among lower-income groups—are known risk factors, but the biological mechanism linking them to persistent pain remains unknown. This research will test whether stress hormones and immune signals can “prime” sensory nerve endings, making them hyper-sensitive long before pain becomes chronic. Using microneurography, a technique that records electrical signals from single nerve fibres in living people, the researcher will measure whether nociceptors in at-risk individuals are already altered. If they are, the team will then test whether resetting the intracellular pathways that maintain this primed state can restore normal nerve function. Success would open a route to prevent chronic pain before it takes hold, rather than treating it after years of suffering. This is fundamental science with a clear translational path: understanding the latent plasticity of pain-sensing nerves could lead to new drugs that interrupt the transition from acute to chronic pain, sparing millions from a condition that currently has no cure.

View original technical description
Devastating for millions, costing the UK economy >£10 billion annually, chronic pain remains poorly understood. While some individuals appear to be primed to develop chronic pain, how these risk factors predispose remains an enigma. Stress and early life adversity, especially prevalent among lower socioeconomic groups, are major risk factors. Pre-clinical evidence indicates unchecked hypothalamic-pituitary-adrenal / sympathoadrenal stress axis activation, along with the resulting pro-inflammatory immune dysregulation, can induce a form of latent pro-nociceptive plasticity in nociceptors, hyperalgesic priming (priming), preceding persistent pain. This latent state provides an opportunity to prevent chronic pain. Employing microneurography to determine sensory nerve stimulus-response properties, I have developed protocols to quantify plasticity at single afferent resolution. I will combine this cutting-edge in-vivo approach with deep sensory phenotyping, in a mechanistic study, to determine if nociceptors in people with, or at risk of developing, chronic pain are primed. I will also identify key neurohumoral and neuroinflammatory factors associated with stress-axis engagement that contribute to priming. Finally, I will test if nociceptor function can be ‘re- set’ by normalising intracellular pathways on which maintenance of priming depends, providing a pathway for novel therapeutics to treat and prevent chronic pain and its co-morbidities.

View the original record at the funder ↗

Researchers

Andrew Marshall (EPMC Awardee)

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Original classification

Career Development Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.