# The role of the AP2 adaptor complex in inflammatory pain

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $63,379

## Abstract

Project Summary
One of the cardinal features of inflammatory states is that normally innocuous stimuli produce pain. Current
pain-relieving drugs include nonsteroidal anti-inflammatory drugs, which are aimed at the interdiction of
prostaglandin production, corticosteroids and opioids. However, the side effects and some cases addiction
potential associated with these drugs limit their long-term use especially during chronic inflammatory pain. To
develop novel, non-addictive analgesics, there remains an urgent need to understand how inflammation
produces the change in nociceptor firing that underlies pain perception. In this proposal, we aim to provide
proof of principal that in dorsal root ganglion (DRG) neurons, adaptin 2 clathrin-mediated endocytosis (AP2-
CME) is a principal facilitator of inflammatory-induced nociceptor sensitization. We have previously
demonstrated that in response to protein kinase A (PKA) stimulation, Slack KNa channels are internalized via
AP2-CME from DRG neuronal membranes and this caused hyperexcitability. Furthermore we showed that
inhibiting AP2-CME prevented PKA-induced neuronal hyperexcitability. Preliminary studies now indicate that in
vivo knockdown of the AP2 alpha subunit AP2A2 specifically within DRG neurons, substantially reduces
inflammatory pain behavior. Here, we will apply a combination of protein chemistry, immunohistochemistry,
electrophysiology, spinal cord physiology, pain behavior assays and a novel in vivo gene knockdown approach
to test the hypothesis that AP2-CME is a key regulator of nociceptor sensitization. The specific aims are 1) to
determine whether AP2-CME controls basal excitability and neurotransmission 2) To demonstrate that
reducing AP2-CME mitigates inflammatory pain. This research project will reveal the central role AP2-CME
plays in pain signaling.

## Key facts

- **NIH application ID:** 10119457
- **Project number:** 3R21NS108087-01A1S2
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Arindam Bhattacharjee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $63,379
- **Award type:** 3
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119457

## Citation

> US National Institutes of Health, RePORTER application 10119457, The role of the AP2 adaptor complex in inflammatory pain (3R21NS108087-01A1S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10119457. Licensed CC0.

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