Extracellular Application of CRMP2 Increases Cytoplasmic Calcium through NMDA Receptors

Castillo, Cecilia; Martı́nez, Juan Carlos; Longart, Marines; García, Lisbeth; Hernández, Marianela; Carballo, Jeismar; Rojas, Héctor; Matteo, Lorena; Casique, Liliana; Escalona, José L.; Rodriguez, Yago; Rodriguez, Jessica; Hernández, Deyanell; Balbi, Domingo; Villegas, Raimundo

doi:10.1016/j.neuroscience.2018.02.002

Cited by 16 publications

(11 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 Collapsin response mediator protein 2 can be released from injured nerves and directly activate NMDA receptors. 4 These receptors are localized both presynaptically and postsynaptically in the SDH. 13,63 Loss of their activation through extracellular CRMP2 may account for at least part of the decreased frequency and amplitude of sEPSCs observed in our studies.…”

Section: Discussionmentioning

confidence: 99%

Conditional knockout of CRMP2 in neurons, but not astrocytes, disrupts spinal nociceptive neurotransmission to control the initiation and maintenance of chronic neuropathic pain

Boinon

Madura

et al. 2021

Pain

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Conditional knockout of CRMP2 in neurons, but not astrocytes, disrupts spinal nociceptive neurotransmission to control the initiation and maintenance of chronic neuropathic pain

Boinon

Madura

et al. 2021

Pain

View full text Add to dashboard Cite

show abstract

“…After an axotomy the nerves undergo a degenerative process leading to multiple biological molecules to be released in the extracellular space. CRMP2 was found to be secreted by degenerating sciatic nerves (Castillo et al, 2018). The CRMP2 found in conditioned media from cultured sciatic nerves can trigger a calcium influx through CaV2.2 and NMDA receptor activation in hippocampal neurons but also in DRG neurons (Castillo et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…CRMP2 was found to be secreted by degenerating sciatic nerves (Castillo et al, 2018). The CRMP2 found in conditioned media from cultured sciatic nerves can trigger a calcium influx through CaV2.2 and NMDA receptor activation in hippocampal neurons but also in DRG neurons (Castillo et al, 2018). This suggests that additionally to its well-known function in ion channel trafficking, CRMP2 could act on the extracellular pool of ion channels and directly activate their function (Moutal and Khanna, 2018).…”

Section: Discussionmentioning

confidence: 99%

Cdk5-mediated CRMP2 phosphorylation is necessary and sufficient for peripheral neuropathic pain

Moutal

Luo

Largent-Milnes

et al. 2019

Neurobiology of Pain

View full text Add to dashboard Cite

Highlights CRMP2 phosphorylation levels are dysregulated in the SNI model of experimental neuropathy. CRMP2 phosphorylation by Cdk5 is increased at the pre-synaptic sites of the dorsal horn of the spinal cord. CRMP2 expression is necessary for neuropathic pain. Genetic targeting of CRMP2 phosphorylation by Cdk5 reverses neuropathic pain. CRMP2 phosphorylation by Cdk5 is sufficient to elicit allodynia.

show abstract

“…which may lead to microglial activation [50]. Interestingly, the novel finding of an extracellular CRMP2 by Castillo and colleagues also raise the possibility of an extracellular CRMP2 participating in chronic pain under autoimmune disease, as well as the signaling between neuronal and glial mechanisms of central sensitization [51,52].…”

Section: Discussionmentioning

confidence: 99%

Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement

et al. 2022

View full text Add to dashboard Cite

Background Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain. Methods NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated. Results We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain. Conclusions Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.

show abstract

Extracellular Application of CRMP2 Increases Cytoplasmic Calcium through NMDA Receptors

Cited by 16 publications

References 70 publications

Conditional knockout of CRMP2 in neurons, but not astrocytes, disrupts spinal nociceptive neurotransmission to control the initiation and maintenance of chronic neuropathic pain

Conditional knockout of CRMP2 in neurons, but not astrocytes, disrupts spinal nociceptive neurotransmission to control the initiation and maintenance of chronic neuropathic pain

Cdk5-mediated CRMP2 phosphorylation is necessary and sufficient for peripheral neuropathic pain

Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement

Contact Info

Product

Resources

About