Looking to better treat pelvic pain arising from such conditions as interstitial cystitis and chronic pelvic pain syndrome, Alison Xie, PhD, an associate research professor in the University of Colorado Department of Surgery, is beginning research on neuromodulation — dulling neural input to manage chronic pain without impacting bladder function.
“We know that when pain becomes chronic, it’s not just about injury or inflammation anymore. The neurons themselves start to misfire — they become hyperactive and hypersensitive,” Xie says. “Eventually, the spinal cord and brain also get pulled in, and the whole system becomes fixed in a painful state. This is what we call centralization.”
Investigating hypersensitivity
Xie’s project will use cutting-edge spatial transcriptomics to uncover how specific cells in the dorsal root ganglia (DRG) — the key nerve hubs that transmit pain from pelvic organs to the spinal cord — become hypersensitive and drive chronic pain.
Using the Visium HD spatial transcriptomics platform, Xie and her team will analyze how different cell types — including neurons, glial cells, and immune cells — interact at single-cell resolution, identifying the precise cell-cell crosstalks that drive pelvic pain and how they differ between sexes.
“In males and females, the pain might feel the same, but we’re finding that the underlying mechanisms are completely different,” Xie says. “In females, we see a much more aggressive immune response that may resolve quickly but causes sharp pain early on. In males, the immune response is slower, while the glial cells drive the neurons to become hypersensitive. That means to prevent chronic pain, we should use different treatments for men and women during the early stage of inflammation or injury — and we’ve never done that before.”
Turn down for pain
Among the study’s goals are mapping DRG cell crosstalks by creating the first spatially resolved map of DRG cell types and how they communicate in healthy tissue and identifying pain signaling pathways and determining how the mechanisms differ by sex.
Xie also plans to explore glial-based analgesia, investigating how modulating glial cells — key support cells in the nervous system — can “turn down” overactive pain signaling without dulling normal sensations.
“The goal is not to shut everything off,” Xie says. “We want to modulate — to reduce the overreaction while still letting neurons monitor our body and remain vigilant.”
Stopping pain at the source
Unlike conventional painkillers, which often suppress all sensory input and can have broad systemic effects, this research could lead to highly targeted therapies.
“We’re aiming for a treatment that could turn off the pain signal at its source, possibly using gene therapy or engineered drugs that only act on the affected cells,” Xie says. “We’re not just masking pain — we’re trying to stop it from becoming chronic."
