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:10.1016/j.bbi.2024.06.019

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

Journal article

Peer reviewed

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

Brain, behavior, and immunity, Vol.120, pp.471-487

08/2024

DOI: 10.1016/j.bbi.2024.06.019

PMCID: PMC12239734

PMID: 38925417

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https://pmc.ncbi.nlm.nih.gov/articles/PMC12239734/pdf/nihms-2090850.pdfView

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Abstract

•Fatigue metabolites, combined with IL-1β, release BDNF from primary DRG neurons.•The effect of BDNF on pain behaviors was observed in male, but not female mice.•There were no sex differences in the changes in expression observed in BDNF. Activity-induced muscle pain increases interleukin-1β (IL-1β) release from muscle macrophages and the development of hyperalgesia is prevented by blockade of IL-1β in muscle. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL-1β and mediates both inflammatory and neuropathic pain. Thus, we hypothesize that in activity-induced pain, fatigue metabolites combined with IL-1β activate sensory neurons to increase BDNF release, peripherally in muscle and centrally in the spinal dorsal horn, to produce hyperalgesia. We tested the effect of intrathecal or intramuscular injection of BDNF-Tropomyosin receptor kinase B (TrkB) inhibitors, ANA-12 or TrkB-Fc, on development of activity-induced pain. Both inhibitors prevented the hyperalgesia when given before or 24hr after induction of the model in male but not female mice. BDNF messenger ribonucleic acid (mRNA) and protein were significantly increased in dorsal root ganglion (DRG) 24hr after induction of the model in both male and female mice. Blockade of IL-1β in muscle had no effect on the increased BNDF mRNA observed in the activity-induced pain model, while IL-1β applied to cultured DRG significantly induced BDNF expression, suggesting IL-1β is sufficient but not necessary to induce BNDF. Thus, fatigue metabolites, combined with IL-1β, upregulate BDNF in primary DRG neurons in both male and female mice, but contribute to activity-induced pain only in males.

Neurons

Pain

Brain-Derived Neurotrophic Factor

Musculoskeletal Pain

Myalgia

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 - Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, IA, USA
Kathleen A. Sluka - University of Iowa
Resource Type: Journal article
Publication Details: Brain, behavior, and immunity, Vol.120, pp.471-487
DOI: 10.1016/j.bbi.2024.06.019
PMID: 38925417
PMCID: PMC12239734
NLM abbreviation: Brain Behav Immun
ISSN: 0889-1591
eISSN: 1090-2139
Publisher: Elsevier Inc
Language: English
Electronic publication date: 06/24/2024
Date published: 08/2024
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984649053702771

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