In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-12-18)
Abstract:
Despite the unpleasant feeling it causes, pain is necessary for survival as it helps individuals to avoid objects, environments and situations that cause damage to their body. However, millions of people experience long-lasting “chronic” pain, or are hypersensitive to pain. There are few treatments available for these conditions, but these treatments do not work well for the majority of patients, and can have serious side effects. To develop new treatments, researchers must first better understand how chronic pain develops. Pain is transmitted to the brain in the form of electrical signals “fired” along nerve fibers. Different nerves transmit information about different types of pain: for example, pain caused by a sharp object pressed against the skin activates a different set of neurons to those activated when touching something dangerously hot. Studies in mice have suggested that a protein called mTOR that is found inside neurons is important for them to fire pain signals. However, it is not clear exactly how mTOR contributes to pain signaling, although it is known to affect the activities of several other proteins in neurons. One protein that mTOR affects the activity of is called 4E-BP1. Now, Khoutorsky, Bonin, Sorge et al. show that mice that lack 4E-BP1 behave in ways that suggest they are hypersensitive to poking or pinching sensations. However, the mice did not show hypersensitivity when they touched a hot surface. Further investigation revealed that the neurons in the spinal cord of mice that lack 4E-BP1 produce abnormally high amounts of a molecule called neuroligin 1, which makes the neurons more likely to fire and thus signal pain. Khoutorsky, Bonin, Sorge et al. found that treating mice that lack 4E-BP1 with a compound that reduces neuroligin 1 production causes their neurons to fire more normally. This also reduces the animals’ apparent signs of hypersensitivity to pressure on their skin. It will be important in future studies to identify additional targets of 4E-BP1 in the spinal cord that could contribute to increased mechanical sensation, and also to study the role of 4E-BP1 in peripheral nerves.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.12002.001
DOI:
10.7554/eLife.12002.002
DOI:
10.7554/eLife.12002.003
DOI:
10.7554/eLife.12002.004
DOI:
10.7554/eLife.12002.005
DOI:
10.7554/eLife.12002.006
DOI:
10.7554/eLife.12002.007
DOI:
10.7554/eLife.12002.008
DOI:
10.7554/eLife.12002.009
DOI:
10.7554/eLife.12002.010
DOI:
10.7554/eLife.12002.011
DOI:
10.7554/eLife.12002.014
DOI:
10.7554/eLife.12002.015
DOI:
10.7554/eLife.12002.012
DOI:
10.7554/eLife.12002.013
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
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