Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice

Kazuhiro Hayashi; Joseph B Lesnak; Ashley N Plumb; Adam J Janowski; Angela F Smith; Joslyn K Hill; Kathleen A Sluka

doi:10.1101/2023.10.31.565022

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Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice

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Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice

Kazuhiro Hayashi, Joseph B Lesnak, Ashley N Plumb, Adam J Janowski, Angela F Smith, Joslyn K Hill and Kathleen A Sluka

bioRxiv : the preprint server for biology

Cold Spring Harbor Laboratory

11/02/2023

DOI: 10.1101/2023.10.31.565022

PMCID: PMC10635076

PMID: 37961342

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https://doi.org/10.1101/2023.10.31.565022View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Activity-induced muscle pain increases release of interleukin-1β (IL-1β) in muscle macrophages and the development of pain is prevented by blockade of IL-1β. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1β and mediates both inflammatory and neuropathic pain. Thus, we hypothesized that metabolites released during fatiguing muscle contractions activate macrophages to release IL-1β, which subsequently activate sensory neurons to secrete BDNF. To test this hypothesis, we used an animal model of activity-induced pain induced by repeated intramuscular acidic saline injections combined with fatiguing muscle contractions. Intrathecal or intramuscular injection of inhibitors of BDNF-Tropomyosin receptor kinase B (TrkB) signaling, ANA-12 or TrkB-Fc, reduced the decrease in muscle withdrawal thresholds in male, but not in female, mice when given before or 24hr after, but not 1 week after induction of the model. BDNF messenger ribonucleic acid (mRNA) was significantly increased in L4-L6 dorsal root ganglion (DRG), but not the spinal dorsal horn or gastrocnemius muscle, 24hr after induction of the model in either male or female mice. No changes in TrkB mRNA or p75 neurotrophin receptor mRNA were observed. BDNF protein expression via immunohistochemistry was significantly increased in L4-L6 spinal dorsal horn and retrogradely labelled muscle afferent DRG neurons, at 24hr after induction of the model in both sexes. In cultured DRG, fatigue metabolites combined with IL-1β significantly increased BDNF expression in both sexes. In summary, fatigue metabolites release, combined with IL-1β, BDNF from primary DRG neurons and contribute to activity-induced muscle pain only in males, while there were no sex differences in the changes in expression observed in BDNF.

Details

Title: Subtitle: Brain-derived neurotrophic factor contributes to activity-induced muscle pain in male but not female mice
Creators: Kazuhiro Hayashi - University of Iowa
Joseph B Lesnak - University of Iowa
Ashley N Plumb - University of Iowa
Adam J Janowski - University of Iowa
Angela F Smith - University of Iowa
Joslyn K Hill
Kathleen A Sluka - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2023.10.31.565022
PMID: 37961342
PMCID: PMC10635076
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 11/02/2023
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984512055202771

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