Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity

Ikutame, Daisuke; Urata, Kentaro; Oto, Tatsuki; Fujiwara, Shintaro; Iinuma, Toshimitsu; Shibuta, Ikuko; Hayashi, Yoshinori; Hitomi, Suzuro; Iwata, Koichi; Shinoda, Masamichi

doi:10.3390/ijms21217871

Cited by 7 publications

(7 citation statements)

References 61 publications

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“…In the spinal cord and thalamic pain nuclei of older adults, primed microglia are activated and resistant to regulation, facilitating the onset of chronic and/or neuropathic pain as well as a state of neuronal hyperexcitability (central sensitization) [45]. In animal models, it has been demonstrated that aging modulates functional changes in the microglia of the trigeminal spinal subnucleus caudalis and regions following palatal mucosal injury, resulting in an enhancement of mechanical allodynia due to the augmentation of neuronal hyperexcitability regulated by age-related microglial activation [55].…”

Section: Spinal Cord and Descending Modulating Systemsmentioning

confidence: 99%

Chronic Pain in the Elderly: Mechanisms and Distinctive Features

Tinnirello¹,

Mazzoleni

Santi

2021

Biomolecules

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Background: Chronic pain is a major issue affecting more than 50% of the older population and up to 80% of nursing homes residents. Research on pain in the elderly focuses mainly on the development of clinical tools to assess pain in patients with dementia and cognitive impairment or on the efficacy and tolerability of medications. In this review, we searched for evidence of specific pain mechanisms or modifications in pain signals processing either at the cellular level or in the central nervous system. Methods: Narrative review. Results: Investigation on pain sensitivity led to conflicting results, with some studies indicating a modest decrease in age-related pain sensitivity, while other researchers found a reduced pain threshold for pressure stimuli. Areas of the brain involved in pain perception and analgesia are susceptible to pathological changes such as gliosis and neuronal death and the effectiveness of descending pain inhibitory mechanisms, particularly their endogenous opioid component, also appears to deteriorate with advancing age. Hyperalgesia is more common at older age and recovery from peripheral nerve injury appears to be delayed. In addition, peripheral nociceptors may contribute minimally to pain sensation at either acute or chronic time points in aged populations. Conclusions: Elderly subjects appear to be more susceptible to prolonged pain development, and medications acting on peripheral sensitization are less efficient. Pathologic changes in the central nervous system are responsible for different pain processing and response to treatment. Specific guidelines focusing on specific pathophysiological changes in the elderly are needed to ensure adequate treatment of chronic pain conditions.

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Section: Spinal Cord and Descending Modulating Systemsmentioning

confidence: 99%

Chronic Pain in the Elderly: Mechanisms and Distinctive Features

Tinnirello¹,

Mazzoleni

Santi

2021

Biomolecules

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“…Groups of mice were formed by cluster random sampling, with two cages housing three mice each being randomly selected and assigned to a group ( n = 6). Group size was determined based on previous studies that employed the same model [ 54 , 55 ]. Behavioral experiments were performed by researchers working in pairs.…”

Section: Methodsmentioning

confidence: 99%

Unveiling Targets for Treating Postoperative Pain: The Role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 Pathways in the Mouse Model of Incisional Pain

Lima

Lauria

Espírito-Santo

et al. 2022

IJMS

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Although the mouse model of incisional pain is broadly used, the mechanisms underlying plantar incision-induced nociception are not fully understood. This work investigates the role of Nav1.8 and Nav1.9 sodium channels in nociceptive sensitization following plantar incision in mice and the signaling pathway modulating these channels. A surgical incision was made in the plantar hind paw of male Swiss mice. Nociceptive thresholds were assessed by von Frey filaments. Gene expression of Nav1.8, Nav1.9, TNF-α, and COX-2 was evaluated by Real-Time PCR in dorsal root ganglia (DRG). Knockdown mice for Nav1.8 and Nav1.9 were produced by antisense oligodeoxynucleotides intrathecal treatments. Local levels of TNF-α and PGE2 were immunoenzymatically determined. Incised mice exhibited hypernociception and upregulated expression of Nav1.8 and Nav1.9 in DRG. Antisense oligodeoxynucleotides reduced hypernociception and downregulated Nav1.8 and Nav1.9. TNF-α and COX-2/PGE2 were upregulated in DRG and plantar skin. Inhibition of TNF-α and COX-2 reduced hypernociception, but only TNF-α inhibition downregulated Nav1.8 and Nav1.9. Antagonizing NF-κB and p38 mitogen-activated protein kinase (MAPK), but not ERK or JNK, reduced both hypernociception and hyperexpression of Nav1.8 and Nav1.9. This study proposes the contribution of the TNF-α/p38/NF-κB/Nav1.8 and Nav1.9 pathways to the pathophysiology of the mouse model of incisional pain.

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“…In the procedure, we used the senescence accelerated mouse prone-8 (SAMP8) strain of mice; however, any mouse strain can be used as a microglia source. The SAMP8 mouse strain exhibits behavioral, morphological and neurochemical changes identified with cognitive decline as well as microglia-associated neuroinflammation [ 16 , 17 ]. Mice were housed in rooms with a 12-h light/dark cycle (20–22°C) with water and food available ad libitum .…”

Section: Methodsmentioning

confidence: 99%

A Simplified Procedure for Isolation of Primary Murine Microglia

2022

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There are various approaches in which one can isolate microglia from murine brains, such as immunomagnetic, density gradient, FACS and differential adhesive methods. In this procedure a modified flask-tapping approach was used due to its simplicity and reproducibility. Our protocol requires only a single step to isolate the microglia from the mixed cell population. Once the microglia were isolated, we characterized cell purity, microglial morphology and phagocytic activity. The single-step protocol, without the need for additional astrocyte or oligodendrocyte separation, allows microglial cells to be used immediately for experimental purposes. The protocol is low-cost and can be performed in any lab with standard cell-culture equipment.

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Aging-Related Phenotypic Conversion of Medullary Microglia Enhances Intraoral Incisional Pain Sensitivity

Cited by 7 publications

References 61 publications

Chronic Pain in the Elderly: Mechanisms and Distinctive Features

Chronic Pain in the Elderly: Mechanisms and Distinctive Features

Unveiling Targets for Treating Postoperative Pain: The Role of the TNF-α/p38 MAPK/NF-κB/Nav1.8 and Nav1.9 Pathways in the Mouse Model of Incisional Pain

A Simplified Procedure for Isolation of Primary Murine Microglia

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