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Published on: February 13, 2018
The role of peptides in central sensitization
1Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church St., S.E., Minneapolis, MN 55455, USA. vseybold@umn.edu
Handbook of Experimental Pharmacology
|August 6, 2009
Summary
Peptides like substance P and CGRP in the spinal cord drive chronic pain by altering nerve signaling. Understanding these mechanisms is key to developing new pain treatments.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Peptides released from nociceptors in the spinal cord contribute to chronic pain and hyperalgesia.
- Substance P (SP) and calcitonin gene-related peptide (CGRP) are key examples of such peptides.
Purpose of the Study:
- To review the mechanisms by which peptidergic neurotransmission contributes to the development and maintenance of chronic pain.
- To explore the roles of SP and CGRP in spinal cord pain signaling.
Main Methods:
- Review of existing literature on peptidergic neurotransmission in chronic pain.
- Analysis of molecular mechanisms involving CGRP and SP receptors.
- Examination of intracellular signaling pathways, including cAMP, phospholipase C, and transcription factors.
Main Results:
- CGRP receptor activation enhances transmitter release and glutamate activation of AMPA receptors via cAMP.
- SP activates neurokinin receptors, leading to membrane depolarization and modulation of AMPA/NMDA receptor function.
- SP also influences prostaglandin and nitric oxide synthesis, acting as retrograde messengers to facilitate nociceptive signaling.
Conclusions:
- Peptidergic neurotransmission, involving SP and CGRP, strengthens synaptic connections between nociceptors and spinal neurons.
- Distinct intracellular pathways activated by SP and CGRP lead to gene expression changes.
- These changes contribute to long-term alterations in spinal neuron excitability, maintaining hyperalgesia and chronic pain.
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