CX3CL1/CX3CR1 regulates nerve injury‐induced pain hypersensitivity through the ERK5 signaling pathway

Sun, Jiao; Xiao, Chengshan; Lu, Bo; Zhang, Juan; Yuan, Xiao-Zong; Chen, Wei; Lu, Yu; Zhang, Fengjiang; Chen, Gang; Yan, Min

doi:10.1002/jnr.23168

Cited by 57 publications

(44 citation statements)

References 32 publications

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“…Animals regained consciousness approximately 1 minute after completion of the injection. The use of AS ODN to manipulate the expression of proteins, essential for their role in nociceptor sensitization, is well supported by previous studies by others (Song et al, 2009, Su et al, 2011, Quanhong et al, 2012, Sun et al, 2013), as well as our group (Parada et al, 2003, Bogen et al, 2012, Alvarez et al, 2014, Araldi et al, 2015, 2016a, Ferrari et al, 2016). …”

Section: Methodssupporting

confidence: 74%

Marked sexual dimorphism in 5-HT 1 receptors mediating pronociceptive effects of sumatriptan

et al. 2017

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Amongst the side effects of triptans, a substantial percentage of patients experience injection site pain and tenderness, the underlying mechanism of which is unknown. We found the dose range from 10 fg – 1000 ng (intradermal) sumatriptan induced a complex dose-dependent mechanical hyperalgesia in the male rat, with distinct peaks, at 1 pg and 10 ng, with no hyperalgesia at 1 ng. In female rats, there was 1 broad peak. The highest dose (1000 ng) did not produce hyperalgesia in either sex. We evaluated the receptors mediating sumatriptan hyperalgesia (1 pg, 1 and 10 ng). In male rats, while the injection of an antagonist for the serotonin (5-hydroxytryptamine, 5-HT) receptor subtype 1B (5-HT1B), but not 5-HT1D, markedly inhibited sumatriptan (1 pg hyperalgesia, at 10 ng a 5-HT1D receptor antagonist completely eliminated hyperalgesia. In contrast, in female rats, the 5-HT1D, but not 5-HT1B, receptor antagonist completely blocked sumatriptan (1 pg and 10 ng) hyperalgesia. Both 5-HT1B and 5-HT1D receptor antagonists attenuated hyperalgesia (1 ng) in females. Sumatriptan (1 ng)-induced hyperalgesia in female rats is G-protein-coupled estrogen receptor 30 dependent. While selective 5-HT1B, but not 5-HT1D, receptor agonists produces a robust hyperalgesia, when co-injected the hyperalgesia induced by 5-HT1B receptor agonist was attenuated. The mechanical hyperalgesia induced by sumatriptan (1 pg and 10 ng) is dependent on the Gi-protein α subunit and protein kinase A (PKA). Understanding the mechanisms responsible for the complex dose dependence for triptan hyperalgesia may provide useful information for the design of anti-migraine drugs with improved therapeutic profiles.

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Section: Methodssupporting

confidence: 74%

Marked sexual dimorphism in 5-HT 1 receptors mediating pronociceptive effects of sumatriptan

et al. 2017

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“…Animals regained consciousness approximately 1 minute after completion of the injection. The use of ODN AS to manipulate the expression of proteins, important for their role in nociceptor sensitization, is well supported by previous studies by others [51; 55; 59; 60], as well as our group [8; 19; 21; 49]. …”

Section: Methodssupporting

confidence: 68%

Adenosine-A1 receptor agonist induced hyperalgesic priming type II

Araldi

Ferrari

Levine

2016

Pain

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We have recently shown that repeated exposure of the peripheral terminal of the primary afferent nociceptor to the mu-opioid receptor (MOR) agonist DAMGO ([D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate salt) induces a model of the transition to chronic pain that we have termed Type II hyperalgesic priming. Similar to Type I hyperalgesic priming, there is a markedly prolonged response to subsequent administration of proalgesic cytokines, prototypically prostaglandin E2 (PGE2). However, Type II hyperalgesic priming differs from Type I in being rapidly induced, protein kinase A (PKA), rather than PKCε dependent, not reversed by a protein translation inhibitor, occurring in female as well as in male rats, and isolectin B4-negative neuron dependent. We report that as with the repeated injection of a MOR agonist, the repeated administration of an agonist at the A1-adenosine receptor, also a Gi-protein coupled receptor, N6-Cyclopentyladenosine (CPA), also produces priming similar to DAMGO-induced Type II hyperalgesic priming. In this study we demonstrate that priming induced by repeated exposure to this A1-adenosine receptor agonist shares the same mechanisms as MOR-agonist induced priming. However, the prolongation of PGE2 hyperalgesia induced by repeated administration of CPA depends on G-protein αi subunit activation, differently from DAMGO-induced Type II priming, in which it depends on the β/γ subunit. These data implicate a novel form of Gi-protein signaling pathway in the Type II hyperalgesic priming induced by repeated administration of an agonist at A1-adenosine receptor to the peripheral terminal of the nociceptor.

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“…It is known that neuropathic pain is a result of injuryinduced peripheral and central neural plasticity (Woolf and Salter, 2000;Ji and Strichartz, 2004). Nerve injuries can induce the activation of ERK5 both in primary afferent neurons and the spinal cord in a neuropathic pain model induced by chronic constriction injury (CCI) or spared nerve injury (SNI) (Sun et al, 2013). After partial nerve injuries, ERK5 activation regulates the expression of the transient receptor potential V1 (TRPV1) and the transient receptor potential A1 (TRPA1).…”

Section: Erk5 Pathway Is Involved In Inflammatory Pain and Neuropathimentioning

confidence: 99%

“…The activation of ERK5 in the spinal cord could contribute to pain hypersensitivity induced by CX3CL1. CX3CL1/ CX3CR1 could mediate the nociceptive signaling between microglia and neurons through ERK5-mediated microglia activation (Sun et al, 2013). In addition, activated microglia in the spinal cord contributes to the initiation of pathological pain responses and the development of neural plasticity after nerve injuries or peripheral inflammation via accelerating the production of proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) (DeLeo and Yezierski, 2001;Watkins and Maier, 2003).…”

Section: Erk5 Activation In the Spinal Dorsal Horn Occurs Mainly In Mmentioning

confidence: 99%

Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain

Sun

Wei

et al. 2016

J. Zhejiang Univ. Sci. B

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Extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1 (MAPK1), is an important member of ERK family, which is a subfamily of the large MAPK family. ERK5 is expressed in many tissues, including the dorsal root ganglion (DRG) neurons and the spinal cord. In this review, we focus on elaborating ERK5-associated pathway in pathological pain, in which the ERK5/CREB (cyclic adenosine monophosphate (cAMP)-response element-binding protein) pathway plays a crucial role in the transduction of pain signal and contributes to pain hypersensitivity. ERK5 activation in the spinal dorsal horn occurs mainly in microglia. The activation of ERK5 can be mediated by N-methyl-D-aspartate (NMDA) receptors. We also elaborate the relationship between ERK5 activation and nerve growth factor-tyrosine kinase A (NGF-TrkA), and the connection between ERK5 activation and brain-derived neurotrophic factor (BDNF) in pathological pain in detail.

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CX3CL1/CX3CR1 regulates nerve injury‐induced pain hypersensitivity through the ERK5 signaling pathway

Cited by 57 publications

References 32 publications

Marked sexual dimorphism in 5-HT 1 receptors mediating pronociceptive effects of sumatriptan

Marked sexual dimorphism in 5-HT 1 receptors mediating pronociceptive effects of sumatriptan

Adenosine-A1 receptor agonist induced hyperalgesic priming type II

Research progress of the role and mechanism of extracellular signal-regulated protein kinase 5 (ERK5) pathway in pathological pain

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