Developmental impact of peripheral injury on neuroimmune signaling

Dourson, Adam J.; Jankowski, Michael P.

doi:10.1016/j.bbi.2023.07.002

Cited by 5 publications

(6 citation statements)

References 156 publications

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“…36,37 ). These and other studies clearly demonstrate that improved therapeutics designed for early life pain are necessary for precision care 38 . Here, we aimed to investigate how early life injury alters the peripheral neuroimmune system to “prime” animals to re-injury later in life.…”

Section: Introductionmentioning

confidence: 66%

“…Following an injury there are both local and global responses in the immune and nervous systems 38 . Macrophages are one of the first immune cells at the injury site to promote inflammation and subsequent wound healing.…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has evaluated the vulnerable periods that exist in the somatosensory and immune systems 5,38,52–57 as well as genetic risk factors in children following surgery 32,58 . After neonatal injury, the inhibitory circuits and microglial activity of the spinal cord dorsal horn (SCDH) are dysregulated leading to hyperactivity of spinal output 59–64 .…”

Section: Discussionmentioning

confidence: 99%

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Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Dourson

Fadaka

Warshak

et al. 2023

Preprint

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These systems are vulnerable to effects of early life injury which can influence outcomes related to nociception following subsequent injury later in life (i.e. neonatal nociceptive priming). The underpinnings of this phenomenon are largely unknown, although macrophages can be epigenetically trained by injury. We found that macrophages are both necessary and partially sufficient to drive neonatal nociceptive priming possibly due to a long-lasting epigenetic remodeling of peripheral macrophages. The p75 neurotrophic factor receptor (NTR) was observed to be an important effector in regulating neonatal nociceptive priming. p75NTR modulates the inflammatory profile and responses of rodent and human macrophages. This pain memory was able to be transferred to a naive host to alter sex-specific pain-related behaviors. This study reveals a novel mechanism by which acute post-surgical pain may transition to chronic pain in children.

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Section: Introductionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Macrophage epigenetic memories of early life injury drive neonatal nociceptive priming

Dourson

Fadaka

Warshak

et al. 2023

Preprint

Self Cite

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show abstract

“…Previous work has evaluated vulnerable periods that exist in the somatosensory and immune systems 5 , 38 , 53 – 58 as well as genetic risk factors in children following surgery. 32 , 59 After neonatal injury, the inhibitory circuits and microglial activity of the spinal cord dorsal horn are dysregulated, leading to hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

“…These and other studies clearly demonstrate that improved therapeutics designed for early-life pain are necessary for precision care. 38 Here, we aimed to investigate how early-life injury alters the peripheral neuroimmune system to “prime” animals to re-injury later in life. We hypothesized that injury-induced epigenetic changes to chromatin accessibility in developing macrophages contribute to neonatal nociceptive priming.…”

Section: Introductionmentioning

confidence: 99%