# Activity-Dependent Nociceptor Sensitization

> **NIH NIH F32** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $66,446

## Abstract

The focus of this proposal is on mechanisms underlying pain, in particular, the sensitization of nociceptive
afferents. Specifically, I proposed to fill a critical gap in our understanding of these mechanisms by characterizing
the contribution of neural activity, in particular, neural activity-dependent increases in intracellular Ca2+ in both
the rapid and the longer-term sensitization of these afferents. Data from previous studies indicate that activity-
dependent changes in gene expression are not only Ca2+ dependent, but dependent on the pattern of activity.
Similarly, a number of ion channels that contribute to the establishment of excitability in sensory neurons are
modulated by a variety of enzymes, that are themselves regulated by changes in intracellular Ca2+. In this
context, I have proposed to focus on voltage-gated sodium channels (VGSCs) for a number of reasons, not the
least of which include a) the essential role these channels play in neural excitability, b) evidence that both rapid
post-translational modifications of these channels, and longer-term changes in channel expression, influence
sensory neuron excitability, and c) because both rapid and longer-term changes in VGSCs have been shown to
be Ca2+ and/or activity dependent. Finally, that the influence of activity on both rapid and longer-term changes
in VGSCs properties may change in the presence of injury, is suggested by the observation that persistent
inflammation results in dramatic changes in the regulation of intracellular Ca2+ in nociceptive afferents, which
includes the almost complete loss of Na+/Ca2+ exchanger (NCX) activity in the sensory neuron somata. Thus, I
hypothesize that dysregulation of intracellular Ca2+, particularly the decrease in NCX activity, contributes to
inflammatory pain via the activity-dependent sensitization of nociceptive afferents secondary to both the rapid
modulation of VGSCs, as well as longer-term changes in the pattern of expression of these channels. To test
this hypothesis, I will characterize the influence of NCX blockade on rapid activity-dependent changes in the
excitability and VGSC properties of mouse and human nociceptive afferents. I will then characterize the influence
of NCX blockade on activity-dependent changes in transcription/translation on the excitability and VGSCs in
mouse and human nociceptive afferents.
 The experiments proposed will not only serve as an excellent training vehicle enabling the mastery of a
variety of powerful techniques and approaches, but will be the first to establish the relationship between the
regulation of intracellular Ca2+ and both rapid and longer-term activity-dependent changes in afferent excitability
and VGSC properties.

## Key facts

- **NIH application ID:** 10021422
- **Project number:** 5F32NS110148-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Jamie Katherine Moy
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $66,446
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021422

## Citation

> US National Institutes of Health, RePORTER application 10021422, Activity-Dependent Nociceptor Sensitization (5F32NS110148-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10021422. Licensed CC0.

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