ArticlePloS one2014
ERK MAP kinase activation in spinal cord regulates phosphorylation of Cdk5 at serine 159 and contributes to peripheral inflammation induced pain/hypersensitivity.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
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- 5Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain.CNS neuroscience & therapeutics · 2023Article
- Activation of GPR183 by 7The Journal of pharmacology and experimental therapeutics · 2022Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- Analgesic Effect of Combined Therapy with the Japanese Herbal Medicine "Medicines (Basel, Switzerland) · 2021Article
- Mechanism of Cdk5-synaptophysin-SNARE pathway in acute and chronic inflammatory pain.American journal of translational research · 2021Article
- Quercetin Ameliorates CFA-Induced Chronic Inflammatory Hyperalgesia via Modulation of ROS-Mediated ERK1/2 Signaling and Inhibition of Spinal Glial Activation In Vivo.Neuromolecular medicine · 2020Article
- Microglial BDNF, PI3K, and p-ERK in the Spinal Cord Are Suppressed by Pulsed Radiofrequency on Dorsal Root Ganglion to Ease SNI-Induced Neuropathic Pain in Rats.Pain research & management · 2019Article
- Identification and characterization of a novel phosphoregulatory site on cyclin-dependent kinase 5.Biochemical and biophysical research communications · 2018Article
- Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Article
- Role of ERK1/2 activation on itch sensation induced by bradykinin B1 activation in inflamed skin.Experimental and therapeutic medicine · 2016Article
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- Convergent phosphomodulation of the major neuronal dendritic potassium channel Kv4.2 by pituitary adenylate cyclase-activating polypeptide.Neuropharmacology · 2016Article
- Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis.Journal of innate immunity · 2016Review
- Long-Term Anti-Allodynic Effect of Immediate Pulsed Radiofrequency Modulation through Down-Regulation of Insulin-Like Growth Factor 2 in a Neuropathic Pain Model.International journal of molecular sciences · 2015Article
- Experimental autoimmune prostatitis induces microglial activation in the spinal cord.The Prostate · 2015Article
- Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord.Neural regeneration research · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase 5 is a proline-directed serine/threonine kinase and its activity participates in the regulation of nociceptive signaling. Like binding with the activators (P35 or P25), the phosphorylation of Cdk5 plays a critical role in Cdk5 activation. However, it is still unclear whether Cdk5 phosphorylation (p-Cdk5) contributes to pain hyperalgesia. The aim of our current study was to identify the roles of p-Cdk5 and its upstream regulator in response to peripheral inflammation. Complete Freund's adjuvant (CFA) injection induced acute peripheral inflammation and heat hyperalgesia, which was accompanied by sustained increases in phospho-ERK1/2 (p-ERK1/2) and phospho-Cdk5(S159) (p-Cdk5(S159)) in the spinal cord dorsal horn (SCDH). CFA-induced p-ERK primarily colocalized with p-Cdk5(S159) in superficial dorsal horn neurons. Levels in p-ERK and p-Cdk5 were also increased in the 2(nd) phase of hyperalgesia induced by formalin injection, which can produce acute and tonic inflammatory pain. MAP kinase kinase inhibitor U0126 intrathecal delivery significantly suppressed the elevation of p-Cdk5(S159), Cdk5 activity and pain response behavior (Heat hyperalgesia, Spontaneous flinches) induced by CFA or formalin injection. Cdk5 inhibitor roscovitine intrathecal administration also suppressed CFA-induced heat hyperalgesia and Cdk5 phosphorylation, but did not attenuate ERK activation. All these findings suggested that p-Cdk5(S159) regulated by ERK pathway activity may be a critical mechanism involved in the activation of Cdk5 in nociceptive spinal neurons contributes to peripheral inflammatory pain hypersensitivity.
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