# Mechanisms of chronic pain maintained by ongoing nociceptor inputs in females

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $345,625

## Abstract

ABSTRACT
Chronic pain afflicts >10% of US adults, with women being disproportionately affected, and constitutes a serious
public health threat associated with overuse/misuse of opioid pain medications. Thus, new pain therapies based
on detailed understanding of chronic pain mechanisms are needed as alternatives to opioid analgesics. Central
sensitization is an important underlying contributor to chronic pain states, but it remains poorly understood how
central sensitization persists when the inciting injury has apparently resolved. This proposal addresses female-
specific mechanisms that maintain persistent central sensitization using a novel animal model that transitions
from acute to chronic pain. This new model is based on the widely-used intradermal capsaicin injection model
that normally develops short-lasting (1-3 days) central sensitization, resulting in mechanical hypersensitivity in
areas outside the capsaicin injection site. We found that subsequent innocuous stimulation (e.g., warmth) of the
capsaicin-injected hindpaw extended the central sensitization to more than two weeks, thus modeling
pathological pain states where acute injury-induced temporary pain transitions to chronic pain despite resolution
of the original injury. Both male and female mice develop persistent central sensitization, but the underlying
mechanism(s) is sexually dimorphic in that a local anesthesia of the original injury site inhibits the persistent
central sensitization only in females. This finding is reminiscent of clinical reports on 5 cases (4 women, 1 man)
of complex regional pain syndrome in which local anesthesia of previous injury sites abolished mechanical
hypersensitivity remote from the sites. Based on this observation and the literature, we hypothesize that the
maintenance of central sensitization in females depends on persistent, ongoing peripheral nerve activity at the
original injury site. We will test this hypothesis using the new female chronic pain model with behavioral,
immunohistochemical, and electrophysiological approaches and determine the peripheral afferent types
persistently active at the original injury site (Aim 1); the underlying molecular mechanism(s) of this persistent
afferent activity (Aim 2); and central components contributing to the central sensitization maintained by
persistent, ongoing afferent nerve activity (Aim 3). The results of this project will provide new knowledge of
previously unrecognized female-specific chronic pain mechanisms and reveal peripheral and central targets for
potential non-opioid chronic pain therapies in women, contributing to development of strategies to combat the
‘opioid epidemic’ caused by overuse/misuse of opioid analgesics.

## Key facts

- **NIH application ID:** 10442735
- **Project number:** 5R01NS112344-04
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Jun-Ho La
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $345,625
- **Award type:** 5
- **Project period:** 2019-06-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442735

## Citation

> US National Institutes of Health, RePORTER application 10442735, Mechanisms of chronic pain maintained by ongoing nociceptor inputs in females (5R01NS112344-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10442735. Licensed CC0.

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