# Role of Pannexin-1 in Chemotherapy-Induced Neuropathic Pain

> **NIH NIH F30** · UNIVERSITY OF VIRGINIA · 2020 · $33,977

## Abstract

PROJECT SUMMARY/ABSTRACT
Neuropathic pain is an incapacitating consequence of cancer treatment with cytotoxic chemotherapeutics, such
as paclitaxel. The economic cost of chronic pain, including neuropathic pain as a large component, has been
estimated to be over $500 billion in the US alone. Existing treatments are largely ineffective, and neuropathic
pain is one of the most common reasons for reducing chemotherapy dosing. Neuropathic pain may be short
term (acute neuropathic pain) or it may persist after multiple doses of chemotherapy (chronic neuropathic
pain). Although mechanisms for pain associated with chemotherapeutic-induced peripheral neuropathy (CIPN)
are not known, other forms of chronic neuropathic pain are often associated with an inflammatory process and
purinergic signaling. Our group previously found that Pannexin 1 (Panx1) channels, which release ATP and
other potentially pro-inflammatory metabolites, are required for development and maintenance of neuropathic
pain after direct nerve injury. Thus, I hypothesize that Panx1 may also contribute to CIPN-associated pain.
My exciting preliminary data from knockout mice reveal a unique role for Panx1 specifically in the transition
from acute to chronic pain. Specifically, Panx1-deleted mice developed acute mechanical hypersensitivity after
an initial bout of paclitaxel, but unlike wild type mice, the neuropathic pain was not maintained and resolved
after a second bout of paclitaxel. In this proposal, I examine the cellular and mechanistic basis for this role of
Panx1 using behavioral assays with paclitaxel-treated mice, along with electrophysiological and immunological
characterization of sensory neurons and immune cells in dorsal root ganglion (DRG). In Aim 1, I use genetic
and pharmacological tools, including global and cell-specific Panx1 knockout mice, to determine the
contribution of Panx1 in hematopoietic cells to chronic neuropathic pain. The hypothesis driving Aim 2 is that
Panx1 is necessary for the persistent inflammation of DRG after repeated bouts of paclitaxel. I use patch
clamp electrophysiology, flow-cytometry, and immunohistochemistry to determine neuron excitability and
inflammatory states of DRG during acute and chronic phase of neuropathic pain. Collectively, this proposal will
provide new information regarding Panx1 involvement in chronic chemotherapy-induced neuropathic pain, and
a rationale for considering Panx1 as a novel target for treating this debilitating side effect of life-saving
cytotoxic chemotherapies.

## Key facts

- **NIH application ID:** 9830503
- **Project number:** 5F30CA236370-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Adishesh Narahari
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,977
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830503

## Citation

> US National Institutes of Health, RePORTER application 9830503, Role of Pannexin-1 in Chemotherapy-Induced Neuropathic Pain (5F30CA236370-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830503. Licensed CC0.

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