Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

Beggs, Simon; Salter, Michael W.

doi:10.1016/j.bbi.2006.10.017

Cited by 129 publications

(94 citation statements)

References 49 publications

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“…In previous studies, an early and transient increase in the number of microglia induced by peripheral nerve injury was also observed. Peripheral nerve injury increased the number of dorsal horn microglia by twofold to fourfold [32][33][34]. The increase in microglia was demonstrated to be associated with proliferation of pre-existing cells, as shown by proliferation markers [35][36][37].…”

Section: Discussionmentioning

confidence: 97%

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Jiang

et al. 2016

Purinergic Signalling

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Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons.

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Section: Discussionmentioning

confidence: 97%

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Jiang

et al. 2016

Purinergic Signalling

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“…Likewise there is abundant evident that PNI induces proliferation of microglia in the dorsal horn 11,20,29 . But there has been no attempt to determine whether this proliferation is in any way linked to a pain phenotype.…”

Section: On Microglial "Markers" Proliferation Infiltration and Neumentioning

confidence: 99%

Microglia–neuronal signalling in neuropathic pain hypersensitivity 2.0

Beggs¹,

Salter²

2010

Current Opinion in Neurobiology

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Microglia are increasingly recognized as critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. The core signalling pathway is through P2X4 purinergic receptors on the microglia which, via the release brain derived neurotrophic factor, cause disinhibition of nociceptive dorsal horn neurons by raising intracellular chloride levels. This disinhibition works in synergy with enhanced excitatory synaptic transmission in the dorsal horn to transform the output of the nociceptive network. There is increased discharge output, unmasking of responses to innocuous peripheral inputs, and spontaneous activity in neurons that otherwise only signal nociception. Together the changes caused by microglia-neuron signalling may account for the main symptoms neuropathic pain in humans.

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“…Under this condition, their morphology, the receptor expression on these cells and their function alter; these cells are ameboid; the markers for activation increase on these cells (8). There is evidence showing that the microglias in the posterior horn of spinal cord are significantly activated after damage to peripheral nerves (9). This suggests that the activation of microglias in the spinal cord is related to the occurrence and transmission of neuropathic pain.…”

Section: Introductionmentioning

confidence: 79%

P2X7 receptor mediates activation of microglial cells in prostate of chemically irritated rats

Zhang

Liu

et al. 2013

Int. braz j urol.

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Purpose: Evidence shows that adenosine triphosphate (ATP) is involved in the transmission of multiple chronic pain via P 2 X 7 receptor. This study was to investigate the P 2 X 7 and microglial cells in the chronic prostatitis pain. Materials and Methods: Rats were divided into control group and chronic prostatitis group (n = 24 per group). A chronic prostatitis animal model was established by injecting complete Freund's adjuvant (CFA) to the prostate of rats, and the thermal withdrawal latency (TWL) was detected on days 0, 4, 12 and 24 (n = 6 at each time point in each group). Animals were sacrificed and the pathological examination of the prostate, detection of mRNA expression of P 2 X 7 and ionized calcium binding adaptor molecule 1 (IBA-1) and measurement of content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the dorsal horn of L 5 -S 2 spinal cord were performed on days 0, 4, 12 and 24. In addition, the content of TNF-α and IL-1β in the dorsal horn of L 5 -S 2 spinal cord was measured after intrathecal injection of inhibitors of microglial cells and/or P 2 X 7 for 5 days. Results: The chronic prostatitis was confirmed by pathological examination. The expression of P 2 X 7 and IBA-1 and the content of TNF-α and IL-1β in rats with chronic prostatitis were significantly higher than those in the control group. On day 4, the expressions of pro-inflammatory cytokines became to increase, reaching a maximal level on day 12 and started to reduce on day 24, but remained higher than that in the control group. Following suppression of microglial cells and P 2 X 7 receptor, the secretion of TNF-α and IL-1β was markedly reduced. Conclusion: In chronic prostatitis pain, the microglial cells and P 2 X 7 receptor are activated resulting in the increased expression of TNF-α and IL-1β in the L 5 -S 2 spinal cord, which might attribute to the maintenance and intensification of pain in chronic prostatitis. INTRODUCTIONChronic prostatitis, a common urological condition in young and middle-age men, is caused by multiple etiological factors. Pain is a major presentation of chronic prostatitis (1). Previous studies focused on the pathological changes in the prostate, while the pathways related to neurotransmission and the regulatory mechanisms of chronic prostatitis pain have not been studied. Recent studies have identified the chronic prostatitis pain as a visceral referred pain, which is usually accompanied by the dysfunction of pelvic floor muscles. The prostate is innervated largely by the pelvic nerves arising from the L 5 -S 2 spinal cord (2,3). P2X7 receptor mediates activation of microglial cells in prostate of chemically irritated rats _______________________________________________ 277It has also been shown that the transmission and regulation of pain are associated with not only the neurons but the microglia and astrocytes (4,5). Studies also demonstrated that astrocytes and microglias may secrete pro-inflammatory cytokines such as tumor necrosis factors (TNF), interleukin-1 (IL-1), nerve growth fac...

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Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

Cited by 129 publications

References 49 publications

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Microglia–neuronal signalling in neuropathic pain hypersensitivity 2.0

P2X7 receptor mediates activation of microglial cells in prostate of chemically irritated rats

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