Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I

Zhou, Jingjing; Zhang, Xiaoxue; Zhou, You; Wu, Bin; Tan, ZC

doi:10.1007/s12264-019-00345-0

Cited by 21 publications

(17 citation statements)

References 29 publications

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“…P2X7Rs are highly expressed in the mPFC, mostly in glial cells ( Inoue and Tsuda, 2009 ; Scholz and Woolf, 2007 ). The finding that antagonists of P2X7R exert an analgesic effect has been verified in extensive experiments ( Chessell et al., 2005 ; Ochi-ishi et al., 2014 ; Xie et al., 2017 ; Zhou et al., 2019 ). When purinergic receptors were blocked, experimental animals showed less bone cancer pain ( Huang et al., 2014 ) and diabetic neuropathic pain ( Guan et al., 2019 ).…”

Section: Discussionmentioning

confidence: 73%

Reduction of prefrontal purinergic signaling is necessary for the analgesic effect of morphine

et al. 2021

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Summary Morphine is commonly used to relieve moderate to severe pain, but repeated doses cause opioid tolerance. Here, we used ATP sensor and fiber photometry to detect prefrontal ATP level. It showed that prefrontal ATP level decreased after morphine injection and the event amplitude tended to decrease with continuous morphine exposure. Morphine had little effect on prefrontal ATP due to its tolerance. Therefore, we hypothesized that the analgesic effect of morphine might be related to ATP in the medial prefrontal cortex (mPFC). Moreover, local infusion of ATP partially antagonized morphine analgesia. Then we found that inhibiting P2X7R in the mPFC mimicked morphine analgesia. In morphine-tolerant mice, pretreatment with P2X4R or P2X7R antagonists in the mPFC enhanced analgesic effect. Our findings suggest that reduction of prefrontal purinergic signaling is necessary for the morphine analgesia, which help elucidate the mechanism of morphine analgesia and may lead to the development of new clinical treatments for neuropathic pain.

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Section: Discussionmentioning

confidence: 73%

Reduction of prefrontal purinergic signaling is necessary for the analgesic effect of morphine

et al. 2021

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“…The P2X7 receptor in DRG modulates afferent nerve activation and is involved in both neuropathic (Xie et al 2017;Wu et al 2017a) and inflammatory pain conditions (Liu et al 2017). Our recent study indicates that activation of P2X7R in microglial cells of spinal cord contributes to the inflammatory pain induced by BmK I (Zhou et al 2019). In the present study, we examined the expression of P2X7 receptors in the SGCs of DRG in the BmK I-induced pain model.…”

Section: Discussionmentioning

confidence: 88%

“…Moreover, the P2X7R plays an important role in the initiation and maintenance of inflammatory and neuropathic pain (Chizh and Illes 2001;Sperlagh et al 2006;Skaper et al 2010). Particularly, recent study indicated that activation of P2X7R in microglial cells of spinal cord contributes to the inflammatory pain induced by BmK I, an activator of sodium channel and a major toxin component of the venom of Asian scorpion Buthus martensi Karsch (BmK) (Zhou et al 2019). In dorsal root ganglion (DRG), P2X7R is selectively expressed in satellite glial cells (SGCs), and is involved in the modulation of nociceptive signals in DRGs (North 2002;Liu and Salter 2005;Nakatsuka and Gu 2006;Chen et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Involvement of P2X7 receptors in satellite glial cells of dorsal root ganglia in the BmK I -induced pain model of rats

Zhou

Feng²,

Zhang³

et al. 2019

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The P2X7 receptor (P2X7R) plays an important role in inflammatory and neuropathic pain. Our recent study indicated that activation of P2X7R in microglial cells of spinal cord contributes to the inflammatory pain induced by BmK I, the major active compound from Buthus martensi Karsch (BmK). In the present study, we further investigated whether P2X7R in satellite glial cells (SGCs) of dorsal root ganglion (DRG) is involved in the BmK I-induced pain in rats. The results found that the expression of P2X7R in SGCs was increased in the ipsilateral side of L4-L5 DRGs after intraplantar injection of BmK I. Moreover, the expression of an inflammatory cytokine IL-1β was increased in DRG after BmK I injection. Systemic administration of an inhibitor of P2X7R (A-438079) significantly inhibited both spontaneous and evoked nociceptive behaviors induced by BmK I. These results suggest that the P2X7R in SGCs of DRG might contribute to pain induced by toxins that sensitize peripheral sensory nerves.

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“…The importance of the involvement of p38MAPK phosphorylation in the development and maintenance of neuropathic pain boosts us to explore the association of p38MAPK phosphorylation and P2X7R activation in mediating BTZ-induced neuropathic pain. P2X7R has a crucial function in chronic pain or neuropathic pain in different pathological conditions, making P2X7R an appealing target for the treatment of intractable neuropathic pain [ 9 , 17 , 21 , 42 – 44 ]. Exploring the expression and activation of P2X7R in DRG and SDH is particularly important for finding novel targets for relieving BTZ-induced neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

“…P2X7R is located in microglia of the central nervous system and in SGCs of the DRG [15,16]. Activation of P2X7R in microglia of the spinal cord and in SGCs of DRG contributes to inflammatory pain [9,17].…”

Section: Introductionmentioning

confidence: 99%

The Actions and Mechanisms of P2X7R and p38 MAPK Activation in Mediating Bortezomib-Induced Neuropathic Pain

Guo

Huang

et al. 2020

BioMed Research International

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The proteasome inhibitor bortezomib (BTZ) is a potent first-line anticancer drug for multiple myeloma; nonetheless, it induced peripheral neuropathy. It has been suggested that many cytokines may play a role in mediating neuropathic pain, but the underlying molecular mechanism is not fully understood. Recent studies have shown that neuropathic pain is closely related to the purinergic ligand-gated ion channel 7 receptor (P2X7R), one of the P2X receptors, which is richly expressed in glial cells. P2X7-p38 pathway is correlated with microglia- and satellite glial cell- (SGC-) mediated neuropathic pain. However, the association of P2X7R and p38MAPK in mediating BTZ-induced neuropathic pain remains unclear. In this study, the relationship between P2X7R activation and p38 phosphorylation in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in the development and maintenance of BTZ-induced neuropathic pain was elucidated. The results showed that BTZ increased mechanical thresholds in rats, accompanied with upregulation of P2X7R expression and p38MAPK phosphorylation, indicating that P2X7R and p38MAPK are key molecules in the development and maintenance of BTZ-induced neuropathic pain. Inhibiting p38MAPK phosphorylation with SB203580 resulted in downregulation of P2X7R expression levels. Inhibition of P2X7R with Brilliant Blue G (BBG) reversed neuropathic pain might decrease through the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 via inhibiting p38MAPK phosphorylation. The P2X7R/p38MAPK signaling pathway in SGCs of DRG and microglia of SDH might be a potential pharmacological target behind this mechanism as an opportunity to relieve BTZ-induced neuropathic pain.

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Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I

Cited by 21 publications

References 29 publications

Reduction of prefrontal purinergic signaling is necessary for the analgesic effect of morphine

Reduction of prefrontal purinergic signaling is necessary for the analgesic effect of morphine

Involvement of P2X7 receptors in satellite glial cells of dorsal root ganglia in the BmK I -induced pain model of rats

The Actions and Mechanisms of P2X7R and p38 MAPK Activation in Mediating Bortezomib-Induced Neuropathic Pain

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