<scp>P2X<sub>7</sub></scp> receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury

Ito, Genta; Suekawa, Y.; Watanabe, Masashi; Takahashi, Kohei; Inubushi, Toshihiro; Murasaki, Kyoko; Hirose, Naoto; Hiyama, Shinji; Uchida, Takuro; Tanne, Kazuo

doi:10.1002/j.1532-2149.2012.00174.x

Cited by 28 publications

(28 citation statements)

References 49 publications

(86 reference statements)

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“…Mice lacking P2X7R show no hypersensitivity to mechanical and thermal stimulation 32 . Moreover, several studies have demonstrated that specific P2X7R antagonists attenuate or completely abolish hypersensitivity to thermal and mechanical stimulation in chronic neuropathic and inflammatory pain models 59–61 . While P2X7R activation has been more extensively studied in chronic pain models, some studies have also reported that P2X7R plays a role in acute inflammation 62, 63 .…”

Section: Discussionmentioning

confidence: 99%

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Muñoz

Gao

Tian

et al. 2017

Sci Rep

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ATP can activate a variety of pathways through P2 purinoreceptors, leading to neuroprotection and pathology in the CNS. Among all P2X receptors, the P2X7 receptor (P2X7R) is a well-defined therapeutic target for inflammatory and neuropathic pain. Activation of P2X7R can generate reactive oxygen species (ROS) in macrophages and microglia. However, the role of ROS in P2X7R–induced pain remains unexplored. Here, we investigated the downstream effects of neuronal P2X7R activation in the spinal cord. We found that ATP induces ROS production in spinal cord dorsal horn neurons, an effect eliminated by ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) and P2X7R antagonist A438079. A similar effect was observed with a P2X7R agonist, BzATP, and was attenuated by a NADPH oxidase inhibitor apocynin. Intrathecal administration of BzATP resulted in ROS production in the spinal cord and oxidative DNA damage in dorsal horn neurons. BzATP also induced robust biphasic spontaneous nociceptive behavior. Pre-treatment with A438079 abolished all BzATP-induced nociceptive behaviors, while ROS scavengers dose-dependently attenuated the secondary response. Here, we provide evidence that neuronal P2X7R activation leads to ROS production and subsequent nociceptive pain in mice. Together, the data indicate that P2X7R-induced ROS play a critical role in the P2X7R signaling pathway of the CNS.

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Section: Discussionmentioning

confidence: 99%

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Muñoz

Gao

Tian

et al. 2017

Sci Rep

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“…The exact mechanism of how TNS reduces inflammation has not been elucidated. However, there is evidence of interaction between the trigeminal nerve and microglia, especially in disease processes such as trigeminal neuralgia (TN) 58, 59 . In animal models, chronic constriction of the trigeminal nerve has been shown to activate microglia resulting in release of pro-inflammatory cytokines 60 .…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain Injury

Chiluwal

Narayan

Chaung

et al. 2017

Sci Rep

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Following traumatic brain injury (TBI), ischemia and hypoxia play a major role in further worsening of the damage, a process referred to as ‘secondary injury’. Protecting neurons from causative factors of secondary injury has been the guiding principle of modern TBI management. Stimulation of trigeminal nerve induces pressor response and improves cerebral blood flow (CBF) by activating the rostral ventrolateral medulla. Moreover, it causes cerebrovasodilation through the trigemino-cerebrovascular system and trigemino-parasympathetic reflex. These effects are capable of increasing cerebral perfusion, making trigeminal nerve stimulation (TNS) a promising strategy for TBI management. Here, we investigated the use of electrical TNS for improving CBF and brain oxygen tension (PbrO2), with the goal of decreasing secondary injury. Severe TBI was produced using controlled cortical impact (CCI) in a rat model, and TNS treatment was delivered for the first hour after CCI. In comparison to TBI group, TBI animals with TNS treatment demonstrated significantly increased systemic blood pressure, CBF and PbrO2 at the hyperacute phase of TBI. Furthermore, rats in TNS-treatment group showed significantly reduced brain edema, blood-brain barrier disruption, lesion volume, and brain cortical levels of TNF-α and IL-6. These data provide strong early evidence that TNS could be an effective neuroprotective strategy.

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“…Central sensitization of nociceptive neurons could be produced by intrathecal superfusion of Bz-ATP and was depressed by P2X7R antagonists [86]. Additional studies extended these findings to mechanisms participating in the development of neuropathic or orofacial pain [87][88][89], bone cancer pain [90] and migraine [91]. Recent studies highlighted the association between human P2X7R variants with chronic pain sensitivity [24].…”

Section: Physiopathology Of P2x7 Receptorsmentioning

confidence: 97%

P2X7 receptor: an emerging target in central nervous system diseases

Sperlágh

Illéš

2014

Trends in Pharmacological Sciences

321

279

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26 27The ATP-sensitive homomeric P2X7 receptor (P2X7R) has received particular 28 attention as a potential drug target because of its widespread involvement in 29 inflammatory diseases as a key regulatory element of the inflammasome 30 complex. However, it has only recently become evident that P2X7Rs also play a 31 pivotal role in central nervous system (CNS) pathology. There is an explosion of 32 data indicating that genetic deletion and pharmacological blockade of P2X7Rs 33 alter responsiveness in animal models of neurological disorders, such as stroke, forming the tail. When co-assembled as a trimeric unit, P2X7R has a chalice-like 65

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P2X₇ receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury

Abstract: Based on these findings, phosphorylation of p38 MAPK via P2X(7)R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF-α released by microglia.

Cited by 28 publications

References 49 publications

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain Injury

P2X7 receptor: an emerging target in central nervous system diseases

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P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury

Abstract: Based on these findings, phosphorylation of p38 MAPK via P2X(7)R may induce tactile allodynia/hyperalgesia, which is most likely mediated by sTNF-α released by microglia.

Cited by 28 publications

References 49 publications

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Neuronal P2X7 receptor-induced reactive oxygen species production contributes to nociceptive behavior in mice

Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain Injury

P2X7 receptor: an emerging target in central nervous system diseases

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Product

Resources

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P2X₇ receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury