Morphological and Functional Roles of Macrophages and Postganglionic Sympathetic Fibers in Dorsal Root Ganglions of a Rat Neuropathic Pain Model.

Matsumoto, Yasunori; Hayashi, Seiji; Ibuki, Takae; Tanaka, Masaki; Ibata, Yasuhiko

doi:10.1267/ahc.32.85

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…According to our electron microscopy study, 5 days after SNL, macrophages in the ring did not actually touch other macrophages, although gap junctions with satellite cells cannot be definitively excluded. Some of the macrophages infiltrated underneath the satellite cell sheath in an "in-pocket" position, as described in DRG 14 days after SNL [72] and in the trigeminal ganglia 7 days after infraorbital nerve ligation [71]. Intriguingly, we noticed that some macrophages were completely engulfed in the neuronal cytoplasm.…”

Section: Discussionsupporting

confidence: 73%

Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain

Gheorghe,

Grosu,

Magercu

et al. 2023

IJMS

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Resident macrophages from dorsal root ganglia are important for the development of traumatic-induced neuropathic pain. In the first 5–7 days after a traumatic sciatic nerve injury (i.e., spinal nerve ligation (SNL), spared nerve injury (SNI), sciatic nerve transection or sciatic nerve ligation and transection), Ionized binding adapter protein 1 (Iba1) (+) resident macrophages cluster around dorsal root ganglia neurons, possibly contributing to nerve injury-induced hypersensitivity. Since infiltrating macrophages gradually recruited to the lesion site peak at about 7 days, the first few days post-lesion offer a window of opportunity when the contribution of Iba1 (+) resident macrophages to neuropathic pain pathogenesis could be investigated. Iba1 is an actin cross-linking cytoskeleton protein, specifically located only in macrophages and microglia. In this study, we explored the contribution of rat Iba1 (+) macrophages in SNL-induced neuropathic pain by using intra-ganglionic injections of naked Iba1-siRNA, delivered at the time the lesion occurred. The results show that 5 days after Iba1 silencing, Iba1 (+) resident macrophages are switched from an M1 (pro-inflammatory) phenotype to an M2 (anti-inflammatory) phenotype, which was confirmed by a significant decrease of M1 markers (CD32 and CD86), a significant increase of M2 markers (CD163 and Arginase-1), a reduced secretion of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) and an increased release of pro-regenerative factors (BDNF, NGF and NT-3) which initiated the regrowth of adult DRG neurites and reduced SNL-induced neuropathic pain. Our data show for the first time, that it is possible to induce macrophages towards an anti-inflammatory phenotype by interacting with their cytoskeleton.

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Section: Discussionsupporting

confidence: 73%

Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain

Gheorghe,

Grosu,

Magercu

et al. 2023

IJMS

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“…A part of the envelope is formed by multiplied SGCs, but ED-1+ macrophages invade near to the neuronal bodies, as well (see Fig. 4j-l; Gehrmann et al 1991;Matsumoto et al 1999;Hu and McLachlan 2002). The ED-1+ macrophages displayed nidogen immunofluorescence when it was decreased in the SGCs.…”

Section: Discussionmentioning

confidence: 94%

A heterogeneous immunofluorescence staining for laminin-1 and related basal lamina molecules in the dorsal root ganglia following constriction nerve injury

Dubový¹,

Jančálek

Klusáková³

2005

Histochem Cell Biol

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The bodies of primary sensory neurons and their satellite glial cells (SGCs) are limited by the basal laminae from extracellular matrix of the dorsal root ganglia (DRG). The basal laminae displayed uniform immunofluorescence staining for laminin-1 in the sections of rat intact (naive) DRG. A proximal or distal ligature of the spinal nerves resulted in a heterogeneous immunostaining for laminin-1 around neuron-SGC units in the sections of the corresponding DRG. The pattern of irregular laminin-1 immunofluorescence was more extensive in the ipsilateral than the contralateral DRG of the operated rats. The immunofluorescence for laminin-1 exactly coincided with binding of Concanavalin-A as well as immunostaining for type IV collagen in both naive DRG and DRG affected by nerve ligature. Nidogen immunostaining decreased or fully disappeared at the surface of the SGCs consistently with immunofluorescence staining for laminin-1, but retained or increased in the endothelial cells and ED-1 positive cells invaded the DRG affected by nerve ligature. The results indicate an alteration of the content of basal laminae surrounding the bodies of primary sensory neurons and their SGSs following nerve constriction injury. A modulation of the basal laminae may be related with other cellular and molecular alterations related with peripheral neuropathic pain, for example, expansion of sympathetic sprouts.

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“…Percent response frequency was calculated for each trial using the following formula: (number of withdrawals/10)´100=% response frequency. Three trials were carried out for each von Frey filament per time point and a mean % response frequency was calculated [13].…”

Section: Mechanical Hyperalgesia and Allodyniamentioning

confidence: 99%

“…Von Frey test was used for quantifying the mechanical and thermal sensitivity of the foot. A brisk withdrawal in response to mechanical or thermal stimuli to the hindpaw was measured using a plastic probe (von Frey filament) [13,18]. As the burn injured area was far away from the foot and hyperalgesia in phase 2 was observed by the fomalin test, we next aimed to examine the histochemical change in the lumbar spinal cord.…”

Section: Introductionmentioning

confidence: 99%

Foot Hyperalgesia after Thoracic Burn Injury. Histochemical, Behavioral and Pharmacological Studies.

Ueda

Hirose

Takei

et al. 2001

Acta Histochem. Cytochem

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Using behavioral, immunohistochemical and pharmacological studies, we report here that large thoracic burn injuries remotely induce hindpaw hyperalgesia during the healing stage. During 2-3 weeks after thoracic burn injury when the skin was regenerating from the wound, we observed by formalin test that the number of flinching behaviors significantly increased and simultaneously we observed by von Frey test that rats developed mechano-hyperalgesia in the foot. In the dorsal horn of the lumbar spinal cord in burn injured rats, c-Fos expression was significantly augmented after plantar formalin injection. The expression of m-opioid receptor in burn injured rats was significantly decreased compared with that in sham operated rats. The expression of substance P and CGRP in the lumbar dorsal horn was not different between burn and sham operated animals. We also observed that intrathecal administration of glutamate receptor antagonists (MK801 and CNQX) but not cyclooxigenase-2 antagonist (NS-398) reversed the threshold of von Frey test on the foot up to the control level at 2 weeks after injury. Collectively, we analyzed a new pain model showing foot hyperalgesia after thoracic burn injury and demonstrated that neurotransmission of glutamate was enhanced at the lumbar spinal cord level by immunocytochemistry and intrathecal administration of NMDA and non NMDA antagonists. Although the precise mechanism of how remote hyperalgesia at the healing stage developed in this model remains to be confirmed, substances such as trophic factors released from the regenerating skin may cause systemic hyperalgesia including in the foot.

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Morphological and Functional Roles of Macrophages and Postganglionic Sympathetic Fibers in Dorsal Root Ganglions of a Rat Neuropathic Pain Model.

Cited by 5 publications

References 46 publications

Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain

Switching Rat Resident Macrophages from M1 to M2 Phenotype by Iba1 Silencing Has Analgesic Effects in SNL-Induced Neuropathic Pain

A heterogeneous immunofluorescence staining for laminin-1 and related basal lamina molecules in the dorsal root ganglia following constriction nerve injury

Foot Hyperalgesia after Thoracic Burn Injury. Histochemical, Behavioral and Pharmacological Studies.

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