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A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
Published on: March 17, 2015
The p75 receptor is associated with inflammatory thermal hypersensitivity
Tomoko Watanabe1, Toshinori Ito, Gen Inoue
1Department of Neurobiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Journal of Neuroscience Research
|August 19, 2008
Summary
Blocking the neurotrophin receptor p75 (p75(NTR)) with antibodies can alleviate inflammatory pain. This approach targets the role of pro-nerve growth factor (pro-NGF) in pain signaling, offering a potential therapeutic strategy.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Inflammatory pain involves a reduced pain threshold due to inflammatory mediators.
- Nerve growth factor (NGF) is a key molecule implicated in inflammatory pain pathways.
- The neurotrophin receptor p75 (p75(NTR)) is involved in sensory neuron function.
Purpose of the Study:
- To investigate the role of p75(NTR) in inflammation-induced hyperalgesia.
- To determine the specific form of NGF (pro-NGF vs. mature NGF) that interacts with p75(NTR) in vivo.
- To explore the therapeutic potential of targeting the NGF/p75(NTR) interaction for inflammatory pain.
Main Methods:
- Administration of neutralizing antibodies against p75(NTR) in rodent models of inflammation.
- Induction of inflammation using complete Freund's adjuvant (CFA) or intraplantar injection of NGF.
- Measurement of calcitonin gene-related peptide (CGRP) levels in primary sensory neurons.
- In vivo assessment of pro-NGF as the predominant ligand for p75(NTR).
- Evaluation of plasmin treatment to decompose pro-NGF and its effect on hyperalgesia.
- Intraplantar injection of pro-NGF to induce hyperalgesia.
Main Results:
- Neutralizing antibodies to p75(NTR) effectively blocked hyperalgesia induced by CFA or NGF.
- Blocking p75(NTR) abolished the CFA-induced upregulation of CGRP in primary sensory neurons.
- Pro-nerve growth factor (pro-NGF) was identified as the predominant ligand for p75(NTR) in vivo.
- Plasmin treatment, degrading pro-NGF, ameliorated CFA-induced hyperalgesia.
- Intraplantar injection of pro-NGF successfully induced hyperalgesia.
Conclusions:
- Both pro-NGF and mature NGF binding to p75(NTR) significantly contribute to inflammation-induced hyperalgesia.
- Targeting the pro-NGF/p75(NTR) interaction presents a promising therapeutic avenue for managing inflammatory pain.
- Interference with NGF binding to p75(NTR) offers a novel strategy for pain relief.
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