Selective androgen receptor modulator microparticle formulation reverses muscle hyperalgesia in a mouse model of widespread muscle pain

Lesnak, Joseph B.; Nakhla, D. S.; Plumb, Ashley; McMillan, Alexandra; Saha, Sanjib; Gupta, Nikesh; Xu, Yan; Phruttiwanichakun, Pornpoj; Rasmussen, Lynn; Meyerholz, David K.; Salem, Aliasger K.; Sluka, Kathleen A.

doi:10.1097/j.pain.0000000000002841

Cited by 3 publications

(1 citation statement)

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“…To test if the changes of BDNF were unique to the activity-induced pain model, the acidic-saline animal model was induced by 2, 20μl pH 4.0 saline injections, separated by 5 days, in the left gastrocnemius muscle [32, 42]. Mice were anesthetized with 2–4% isoflurane and given i.m.…”

Section: Methodsmentioning

confidence: 99%

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

Hayashi,

Lesnak,

Plumb

et al. 2023

Preprint

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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.

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Section: Methodsmentioning

confidence: 99%

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

Hayashi,

Lesnak,

Plumb

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

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

Hayashi,

Lesnak,

Plumb

et al. 2024

Brain, Behavior, and Immunity

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Female specific interactions of serotonin and testosterone in the rostral ventromedial medulla after activity-induced muscle pain

Plumb,

Lesnak,

Rasmussen

et al. 2025

The Journal of Pain

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Selective androgen receptor modulator microparticle formulation reverses muscle hyperalgesia in a mouse model of widespread muscle pain

Abstract: Supplemental Digital Content is Available in the Text.A novel selective androgen receptor modulator (SARM) microparticle formulation allows for safe, extended release of SARM to alleviate muscle hyperalgesia in male and female mice.

Cited by 3 publications

References 84 publications

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

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

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

Female specific interactions of serotonin and testosterone in the rostral ventromedial medulla after activity-induced muscle pain

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