MAP kinase and pain

By R. Ji, R. Gereau, M. Malcangio, G. Strichartz. Brain Research Reviews, 2008

999 citations recorded by the source corpus.

Mitogen-activated protein kinases (MAPKs) are important for intracellular signal transduction and play critical roles in regulating neural plasticity and inflammatory responses. The MAPK family consists of three major members: extracellular signal-regulated kinases (ERK), p38, and c-Jun N-terminal kinase (JNK), which represent three separate signaling pathways. Accumulating evidence shows that all three MAPK pathways contribute to pain sensitization after tissue and nerve injury via distinct molecular and cellular mechanisms. Activation (phosphorylation) of MAPKs under different persistent pain conditions results in the induction and maintenance of pain hypersensitivity via non-transcriptional and transcriptional regulation. In particular, ERK activation in spinal cord dorsal horn neurons by nociceptive activity, via multiple neurotransmitter receptors, and using different second messenger pathways plays a critical role in central sensitization by regulating the activity of glutamate receptors and potassium channels and inducing gene transcription. ERK activation in amygdala neurons is also required for inflammatory pain sensitization. After nerve injury, ERK, p38, and JNK are differentially activated in spinal glial cells (microglia vs astrocytes), leading to the synthesis of proinflammatory/pronociceptive mediators, thereby enhancing and prolonging pain. Inhibition of all three MAPK pathways has been shown to attenuate inflammatory and neuropathic pain in different animal models. Development of specific inhibitors for MAPK pathways to target neurons and glial cells may lead to new therapies for pain management. Although it is well documented that MAPK pathways can increase pain sensitivity via peripheral mechanisms, this review will focus on central mechanisms of MAPKs, especially ERK.

Subfields: Genetics, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/c1811fa99cd45a29dbcfb076f965b9e8830a0173

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

1. Alban Latremoliere
2. Clifford J. Woolf

In Molecular Biology

1. R. Ji
2. Clifford J. Woolf
3. Alban Latremoliere
4. M. Malcangio
5. Maiken Nedergaard
6. Arne May

In Physiology

1. Clifford J. Woolf
2. R. Ji
3. Alban Latremoliere
4. T. Berta
5. Maiken Nedergaard
6. M. Malcangio
7. G. Moalem-Taylor
8. P. Austin

Citations in the corpus

• Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity (2009, positive): “Release of cytokines by microglia increases neuronal excitability through activation of ERK and CREB.(131,142) Activated microglia also release BDNF and NO,(58,116) promoting segmental disinhibition.”
• Glia and pain: Is chronic pain a gliopathy? (2013, background): “It has been shown that GFAP and CD11b upregulation peaks at 150 and 14 days after nerve injury, respectively, although CD11b upregulation remains after 150 days [298].”
• The role of glia in the spinal cord in neuropathic and inflammatory pain. (2015, background): “2009), a mitogen-activated kinase (MAPK) associated with the synthesis and release of pro-nociceptive mediators (Ji et al. 2009).”