Microglia-independent peripheral neuropathic pain in male and female mice

Tu, YuShan; Muley, Milind M.; Beggs, Simon; Salter, Michael W.

doi:10.1097/j.pain.0000000000002643

Cited by 25 publications

(16 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zhang et al, 2016). These macrophages release BDNF and BDNF-TrkB plays an important role in both the initiation and maintenance of the mechanical hypersensitivity of NP (Tu et al, 2022;Yu et al, 2020). Yu et al (2020) also demonstrated that depletion of DRG macrophages prevented the upregulation of BDNF within 24 h of nerve injury in mice (Yu et al, 2020).…”

Section: Spinal Dorsal Horn Dorsal Root Ganglia and Microglia Mediate...mentioning

confidence: 91%

“…Following nerve injury, Michael et al demonstrated an increase in BDNF expression in the TrkC and TrkB receptors (Michael, 1999). Similar to the role of microglia in NP, nerve injury also leads to activation and recruitment of macrophages in the DRG (Malcangio, 2019;Tu et al, 2022;Yu et al, 2020;H. Zhang et al, 2016).…”

Section: Spinal Dorsal Horn Dorsal Root Ganglia and Microglia Mediate...mentioning

confidence: 96%

“…demonstrated an increase in BDNF expression in the TrkC and TrkB receptors (Michael, 1999). Similar to the role of microglia in NP, nerve injury also leads to activation and recruitment of macrophages in the DRG (Malcangio, 2019; Tu et al., 2022; Yu et al., 2020; H. Zhang et al., 2016). These macrophages release BDNF and BDNF‐ TrkB plays an important role in both the initiation and maintenance of the mechanical hypersensitivity of NP (Tu et al., 2022; Yu et al., 2020).…”

Section: Bdnf Related Mechanism Of Action In Npmentioning

confidence: 99%

“…Previous studies have described the interaction of BDNF‐TrkB signaling with N‐methyl‐d‐aspartate (NMDA) receptors as an underlying mechanism that contributes to central sensitization of spinal neurons (Kerr et al., 1999; Latremoliere & Woolf, 2009; Trang et al., 2011). Animal models of NP have revealed that BDNF‐TrkB signaling promotes the upregulation of NR2B, a subunit of NMDA receptors via activation of the mTOR pathway (L. Zhang et al, 2016).…”

Section: Bdnf Related Mechanism Of Action In Npmentioning

confidence: 99%

See 3 more Smart Citations

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

Thakkar

Acevedo

2023

Brain and Behavior

View full text Add to dashboard Cite

Introduction:The primary objective of this paper is to (1) provide a summary of human studies that have used brain derived neurotrophic factor (BDNF) as a biomarker, (2) review animal studies that help to elucidate the mechanistic involvement of BDNF in the development and maintenance of neuropathic pain (NP), and (3) provide a critique of the existing measurement techniques to highlight the limitations of the methods utilized to quantify BDNF in different biofluids in the blood (i.e., serum and plasma) with the intention of presenting a case for the most reliable and valid technique. Lastly, this review also explores potential moderators that can influence the measurement of BDNF and provides recommendations to standardize its quantification to reduce the inconsistencies across studies. Methods:In this manuscript we examined the literature on BDNF, focusing on its role as a biomarker, its mechanism of action in NP, and critically analyzed its measurement in serum and plasma to identify factors that contribute to the discrepancy in results between plasma and serum BDNF values.Results: A large heterogenous literature was reviewed that detailed BDNF's utility as a potential biomarker in healthy volunteers, patients with chronic pain, and patients with neuropsychiatric disorders but demonstrated inconsistent findings. The literature provides insight into the mechanism of action of BDNF at different levels of the central nervous system using animal studies. We identified multiple factors that influence the measurement of BDNF in serum and plasma and based on current evidence, we recommend assessing serum BDNF levels to quantify peripheral BDNF as they are more stable and sensitive to changes than plasma BDNF. Conclusion:Although mechanistic studies clearly explain the role of BDNF, results from human studies are inconsistent. More studies are needed to evaluate the methodological challenges in using serum BDNF as a biomarker in NP.

show abstract

Section: Spinal Dorsal Horn Dorsal Root Ganglia and Microglia Mediate...mentioning

confidence: 91%

Section: Spinal Dorsal Horn Dorsal Root Ganglia and Microglia Mediate...mentioning

confidence: 96%

Section: Bdnf Related Mechanism Of Action In Npmentioning

confidence: 99%

Section: Bdnf Related Mechanism Of Action In Npmentioning

confidence: 99%

See 2 more Smart Citations

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

Thakkar

Acevedo

2023

Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…Depletion of muscle macrophages prior to induction of the pain model prevents development of muscle hyperalgesia (11)(12)(13), and depletion of P2X4 from muscle macrophages prevents hyperalgesia in both male and female mice (14). Similarly, in models of neuropathic pain, macrophages at the site of injury play a key role in the production of hyperalgesia (15,16), suggesting local immune mechanisms are important for pain development. Further, regular physical activity alters macrophage phenotype in skeletal muscle by increasing the number of anti-inflammatory macrophages (M2), and blockade of antiinflammatory cytokine receptors (IL-4, IL-10) at the site of insult prevents the analgesia produced by regular physical activity (13,(17)(18)(19)(20); however, these studies were only done in male mice.…”

Section: Introductionmentioning

confidence: 99%

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

Lesnak

Hayashi

Plumb

et al. 2022

Preprint

View full text Add to dashboard Cite

Induction of muscle pain triggers a local immune response to produce pain and this mechanism may be sex and activity level dependent. The purpose of this study was to measure the immune system response in the muscle following induction of pain in sedentary and physically active mice. Muscle pain was produced via an activity-induced pain model using acidic saline combined with fatiguing muscle contractions. Prior to induction of muscle pain, mice (C57/BL6) were sedentary or physically active (24hr access to running wheel) for 8 weeks. The ipsilateral gastrocnemius was harvested 24hr after induction of muscle pain for RNA sequencing or flow cytometry. RNA sequencing revealed activation of several immune pathways in both sexes after induction of muscle pain, and these pathways were attenuated in physically active females. Uniquely in females, the antigen processing and presentation pathway with MHC II signaling was activated after induction of muscle pain; activation of this pathway was blocked by physical activity. Blockade of MHC II attenuated development of muscle hyperalgesia exclusively in females. Induction of muscle pain increased the number of macrophages and T-cells in the muscle in both sexes, measured by flow cytometry. In both sexes, the phenotype of macrophages shifted toward a pro-inflammatory state after induction of muscle pain in sedentary mice (M1+M1/2) but toward an anti-inflammatory state in physically active mice (M2+M0). Thus, induction of muscle pain activates the immune system with sex-specific differences in the transcriptome while physical activity attenuates immune response in females and alters macrophage phenotype in both sexes.

show abstract

Sexually dimorphic effects of pexidartinib on nerve injury‐induced neuropathic pain in mice

Saika,

Fukazawa,

Hatano

et al. 2024

Glia

View full text Add to dashboard Cite

It is well‐established that spinal microglia and peripheral macrophages play critical roles in the etiology of neuropathic pain; however, growing evidence suggests sex differences in pain hypersensitivity owing to microglia and macrophages. Therefore, it is crucial to understand sex‐ and androgen‐dependent characteristics of pain‐related myeloid cells in mice with nerve injury‐induced neuropathic pain. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony‐stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL). Following PSL induction, healthy male and female mice and male gonadectomized (GDX) mice exhibited similar levels of spinal microglial activation, peripheral macrophage accumulation, and mechanical allodynia. Treatment with PLX3397 significantly suppressed mechanical allodynia in normal males; this was not observed in female and GDX male mice. Sex‐ and androgen‐dependent differences in the PLX3397‐mediated preventive effects were observed on spinal microglia and dorsal root ganglia (DRG) macrophages, as well as in expression patterns of pain‐related inflammatory mediators in these cells. Conversely, no sex‐ or androgen‐dependent differences were detected in sciatic nerve macrophages, and inhibition of peripheral CC‐chemokine receptor 5 prevented neuropathic pain in both sexes. Collectively, these findings demonstrate the presence of considerable sex‐ and androgen‐dependent differences in the etiology of neuropathic pain in spinal microglia and DRG macrophages but not in sciatic nerve macrophages. Given that the mechanisms of neuropathic pain may differ among experimental models and clinical conditions, accumulating several lines of evidence is crucial to comprehensively clarifying the sex‐dependent regulatory mechanisms of pain.

show abstract

Microglia-independent peripheral neuropathic pain in male and female mice

Cited by 25 publications

References 90 publications

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

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

Sexually dimorphic effects of pexidartinib on nerve injury‐induced neuropathic pain in mice

Contact Info

Product

Resources

About