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Updated: Aug 12, 2025

Author Spotlight: Exploring Peripheral Mechanisms of Neuropathic Pain in Trigeminal Nerve Injury
Published on: February 9, 2024
MNK1 and MNK2 expression in the human dorsal root and trigeminal ganglion
Stephanie Shiers1, James J Sahn2, Theodore J Price1
1Center for Advanced Pain Studies, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, Texas, USA.
Abstract:
Mitogen activated protein kinase interacting kinases (MNK) 1 and 2 are serine/threonine protein kinases that play an important role in translation of mRNAs through their phosphorylation of the RNA 5’-cap binding protein, eukaryotic translation initiation factor (eIF) 4E. These kinases are downstream targets for mitogen activated protein kinases (MAPKs), extracellular activity regulated protein kinase (ERK) and p38. MNKs have been implicated in the sensitization of peripheral nociceptors of the dorsal root and trigeminal ganglion (DRG and TG) using transgenic mouse lines and through the use of specific inhibitors of MNK1 and MNK2. While specific knockout of the Mknk1 gene suggests that it is the key isoform for regulation of nociceptor excitability and nociceptive behaviors in mice, both MKNK1 and MKNK2 genes are expressed in the DRG and TG of mice and humans based on RNA sequencing experiments. Single cell sequencing in mice suggests that Mknk1 and Mknk2 may be expressed in different populations of nociceptors. We sought to characterize mRNA expression in human DRG and TG for both MNK1 and MNK2. Our results show that both genes are expressed by nearly all neurons in both human ganglia with expression in other cell types as well. Our findings provide evidence that MNK1 and MNK2 are expressed by human nociceptors and suggest that efforts to pharmacologically target MNKs for pain would likely be translatable due its conserved expression in both species.
Insights
Mitogen activated protein kinase interacting kinases (MNK) 1 and 2 are expressed in human pain-sensing neurons. This conserved expression suggests targeting MNKs could be a viable strategy for pain management.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Mitogen activated protein kinase interacting kinases (MNK) 1 and 2 are crucial for mRNA translation via eIF4E phosphorylation.
- MNKs are downstream targets of MAPKs (ERK, p38) and implicated in nociceptor sensitization.
- Previous studies in mice suggest Mknk1 is key for nociceptor excitability, but both Mknk1 and Mknk2 are expressed in DRG and TG.
Approach:
- Investigated mRNA expression of MNK1 and MNK2 in human dorsal root ganglia (DRG) and trigeminal ganglia (TG).
- Utilized RNA sequencing to analyze gene expression patterns in human sensory ganglia.
Key Points:
- Both MNK1 and MNK2 genes are expressed in nearly all neurons within human DRG and TG.
- Expression was also detected in other cell types within these ganglia.
- This widespread expression indicates MNK1 and MNK2 are present in human nociceptors.
Conclusions:
- MNK1 and MNK2 are expressed in human nociceptors, consistent with findings in mice.
- The conserved expression pattern suggests that pharmacological targeting of MNKs for pain relief is likely translatable across species.

