Mechanical allodynia but not thermal hyperalgesia is impaired in mice deficient for ERK2 in the central nervous system
Abstract
Extracellular signal-regulated kinase (ERK) plays critical roles in pain plasticity. However, the specific contribution of ERK2 isoforms to pain plasticity is not necessarily elucidated. Here we investigate the function of ERK2 in mouse pain models. We used the Cre-loxP system to cause a conditional, region-specific, genetic deletion of Erk2. To induce recombination in the central nervous system, Erk2-floxed mice were crossed with nestin promoter-driven cre transgenic mice. In the spinal cord of resultant Erk2 conditional knockout (CKO) mice, ERK2 expression was abrogated in neurons and astrocytes, but indistinguishable in microglia compared to controls. Although Erk2 CKO mice showed a normal baseline paw withdrawal threshold to mechanical stimuli, these mice had a reduced nociceptive response following a formalin injection to the hind paw. In a partial sciatic nerve ligation model, Erk2 CKO mice showed partially restored mechanical allodynia compared to control mice. Interestingly, thermal hyperalgesia was indistinguishable between Erk2 CKO and control mice in this model. In contrast to Erk2 CKO mice, mice with a targeted deletion of ERK1 did not exhibit prominent anomalies in these pain models. In Erk2 CKO mice, compensatory hyperphosphorylation of ERK1 was detected in the spinal cord. However, ERK1 did not appear to influence nociceptive processing because the additional inhibition of ERK1 phosphorylation using MEK (MAPK/ERK kinase) inhibitor SL327 did not produce additional changes in formalin-induced spontaneous behaviors in Erk2 CKO mice. Together, these results indicate that ERK2 plays a predominant and/or specific role in pain plasticity, while the contribution of ERK1 is limited.
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Genetic abrogation of ERK2 has profound deleterious effects on neural functioning, whereas Erk1 KO mice do not exhibit significant impairment in neural functioning.
“For instance, genetic abrogation of ERK2 has profound deleterious effects on neural functioning, whereas Erk1 KO mice do not exhibit significant impairment in neural functioning10192021.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [19]
Many studies reporting that ERK1 and ERK2 play distinct roles in neuronal functioning.
“There are many studies reporting that ERK1 and ERK2 play distinct roles in neuronal functioning.”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [19]
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- Authors
- Otsubo, Y., Satoh, Y., Kodama, M., Araki, Y., Satomoto, M., Sakamoto, E., Pagès, G., Pouysségur, J., Endo, S., & Kazama, T.
- Affiliations
- Tokyo Medical and Dental University (JP)
- National Defense Medical College Hospital (JP)
- Centre National de la Recherche Scientifique (FR)
- Tokyo Metropolitan Institute of Gerontology (JP)
- Corresponding author
- Satoh, Yasushi
- Venue
- Pain
- Published
- 2012-11
- Volume
- 153
- Issue
- 11
- Pages
- 2241-2252
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2015026911
- Cited by
- 33
- References
- 34
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (23593009)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- ERK2, ERK1, mechanical allodynia, thermal hyperalgesia, pain plasticity, conditional knockout mice, spinal cord, formalin-induced nociception, sciatic nerve ligation, MEK inhibition, SL327, Nestin-Cre, astrocytes, microglia
- MeSH terms
- Animals, Disease Models, Animal, Female, Hyperalgesia, Male, Mice, Inbred C57BL, Mice, Knockout, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 3, Mice
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