# CELLULAR AND ION CHANNEL MECHANISMS UNDERLYING THE SENSE OF LIGHT TOUCH IN MAMMAL

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $439,325

## Abstract

ABSTRACT: Tactile sensitivity of detecting gentle mechanical stimuli or touch is critically important in life but
can be impaired to result in reduction/loss of tactile sensitivity (numbness) under pathological conditions.
Numbness is the earliest and most common symptom of chemotherapy-induced peripheral neuropathy (CIPN)
that negatively impacts quality of life in cancer patients, and it is a dose-limiting factor of chemotherapy.
Numbness of CIPN is poorly treated and its underlying mechanism understudied. This lack of knowledge
prevents development of effective management for numbness CIPN. ♦ A Merkel disc is a main type of tactile
end organ located in touch sensitive spots throughout the body but most abundant at the human fingertips and
whisker hair follicles of all non-primate mammals. A Merkel disc consists of a Merkel cell and an Aβ-afferent
ending to form a synapse-like structure. We and others have recently discovered that tactile stimuli to Merkel
discs are largely transduced in Merkel cells by Piezo2 channels, which drive most Aβ-afferent impulses and
behavioral tactile responses. More recently, we have further identified that Merkel discs in whisker hair follicles
are serotonergic synapses, and serotonin is released from Merkel cells in response to tactile stimuli to
subsequently drive Aβ-afferent impulses and behavioral tactile responses. ♦ In this renewal application, our
new focuses are to study how tactile sensitivity at Merkel discs is modulated and whether the tactile sensitivity
can be impaired by chemotherapy drugs to account for the numbness aspect of CINP. ♦ We propose to use
whisker hair follicle preparation to address these questions with 3 specific aims: Aim 1) Elucidate
mechanisms underlying the modulation of Merkel disc tactile sensitivity. This Aim will focus on whether
serotonin transporters play a key role in regulating Merkel disc serotonergic transmission and Merkel disc
tactile sensitivity. Aim 2: Determine whether and how chemotherapy drugs impair Merkel disc tactile
sensitivity. This Aim will measure changes of serotonergic transmission and Merkel disc tactile sensitivity
following chemotherapy drug treatment, and identify pre- and postsynaptic molecules at Merkel discs that are
targeted by chemotherapy drugs to result in the impairment of Merkel disc tactile sensitivity. Aim 3: Determine
whether targeting Merkel discs by chemotherapy drugs leads to impairment of behavioral tactile
responses. This Aim will determine whether chemotherapy drugs can impair whisker tactile behavioral
responses via suppressing Merkel disc serotonergic transmission, and whether potentiation of Merkel disc
serotonergic transmission by pharmacologically manipulating serotonin transporters can rescue the impaired
whisker tactile behavioral responses. ♦ Completion of the 3 Aims will fill a scientific gap about tactile sensitivity
of mammals, elucidate novel mechanisms underlying numbness aspect of CIPN, and identify potential
therapeutic ...

## Key facts

- **NIH application ID:** 10240307
- **Project number:** 5R01DE023090-11
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JIANGUO GU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $439,325
- **Award type:** 5
- **Project period:** 2013-09-01 → 2023-06-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240307

## Citation

> US National Institutes of Health, RePORTER application 10240307, CELLULAR AND ION CHANNEL MECHANISMS UNDERLYING THE SENSE OF LIGHT TOUCH IN MAMMAL (5R01DE023090-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10240307. Licensed CC0.

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