The impact of sex and physical activity on the local immune response to muscle pain

Lesnak, Joseph B.; Hayashi, Kazuhiro; Plumb, Ashley; Janowski, Adam; Chimenti, Michael S.; Sluka, Kathleen A.

doi:10.1016/j.bbi.2023.03.020

Cited by 8 publications

(3 citation statements)

References 92 publications

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“…Previous studies have shown that PA can affect the expression of inflammatory factors (e.g., IL-6 and IL-10) in the serum of the elderly (Jankord and Jemiolo, 2004). Moreover, current studies have discovered that local immune reactions are related to aching muscles and that regular PA increases the percentage of skeletal muscle regulatory macrophages (M2, which secrete anti-inflammatory cytokines) and increases IL-10 (an anti-inflammatory factor) in Frontiers in Cell and Developmental Biology frontiersin.org mice to prevent chronic pain (Leung et al, 2016;Lesnak et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Causal association of physical activity with low back pain, intervertebral disc degeneration and sciatica: a two-sample mendelian randomization analysis study

Guan,

Zhang,

Zhang

et al. 2023

Front. Cell Dev. Biol.

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Objective: Previous studies are insufficient to confirm a causal association between physical activity (PA) and low back pain (LBP), intervertebral disc degeneration (IDD), and sciatica. The present study used a two-sample Mendelian randomization (MR) analysis method to demonstrate whether or not there was a causal connection.Methods: First, four PA phenotypes were selected [accelerometer-based PA (average acceleration), accelerometer-based PA (acceleration fraction >425 mg), self-reported moderate-to-vigorous PA, and self-reported vigorous PA], setting thresholds for single nucleotide polymorphisms (SNPs) significantly concerned with PA p < 5 × 10−8, linkage disequilibrium (LD) r2 < 0.01, genetic distance >5,000 kb, and F-value >10. SNPs associated with the outcome and confounding factors were then excluded using the PhenoScanncer database. Finally, after coordinating the genetic instruments from genome-wide association studies (GWAS) effect alleles for exposure and outcomes, multiplicative random effects inverse variance weighting (IVW), MR-Egger, weighted median method (WMM), and weighted mode method were used to assess exposure-outcome causality and perform sensitivity analysis on the estimated results.Results: The current study’s IVW findings revealed proof of a causal connection between PA and LBP. While there was a positive causal tie between accelerometer-based PA (acceleration fraction >425 mg) and LBP [OR: 1.818, 95% CI:1.129–2.926, p = 0.012], there was a negative causal link between accelerometer-based PA (average acceleration) and LBP [OR: 0.945, 95% CI: 0.909–0.984, p = 0.005]. However causal relationship between PA and IDD or sciatica was not found.Conclusion: Increasing average PA but needing to avoid high-intensity PA may be an effective means of preventing low back pain. Although PA is not directly causally related to disc degeneration and sciatica, it can act through indirect pathways.

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Section: Discussionmentioning

confidence: 99%

Causal association of physical activity with low back pain, intervertebral disc degeneration and sciatica: a two-sample mendelian randomization analysis study

Guan,

Zhang,

Zhang

et al. 2023

Front. Cell Dev. Biol.

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“…Consistent with the role of hormones in modulating pain, we have shown that testosterone protects against the development of widespread pain in the activity-induced pain model [78], with orchiectomy producing widespread pain similar to females and testosterone producing unilateral pain similar to males. Further, we have shown female-specific mechanisms of pain in the activity-induced pain model where there was activation of the antigen processing and presentation pathway in the muscle, and blockade of MHC II attenuated development of muscle hyperalgesia [79]. Centrally, females but not males, also have greater serotonin transporter immunoreactivity in the nucleus raphe magnus [78].…”

Section: Discussionmentioning

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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“…10,16 Several reports suggested that CD44 activation in macrophages by HMWH can suppress the release of pronociceptive cytokines from tissue-infiltrating macrophages in rodents. 19,22 Furthermore, macrophages have been widely reported to be involved in the development of musculoskeletal pain 11,12,14,18 and have been specifically implicated in muscle pain development as a consequence of extracellular membrane hyaluronan disruption by hyaluronidase administration. 18 Local administration of HMWH has been shown to reduce the infiltration of immune cells in a rodent model of radicular pain postlaminectomy, 15 suggesting a potential use in surgical settings.…”

Section: Other Potential Targets For High-molecular-weight Hyaluronanmentioning

confidence: 99%

A novel potential strategy for the treatment of inflammatory and neuropathic pain

Queme

2023

Pain

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The impact of sex and physical activity on the local immune response to muscle pain

Cited by 8 publications

References 92 publications

Causal association of physical activity with low back pain, intervertebral disc degeneration and sciatica: a two-sample mendelian randomization analysis study

Causal association of physical activity with low back pain, intervertebral disc degeneration and sciatica: a two-sample mendelian randomization analysis study

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

A novel potential strategy for the treatment of inflammatory and neuropathic pain

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