It has long been assumed that chronic nerve pain is caused by hypersensitivity in the neurons that transmit pain. Researchers now show that another kind of neuron that normally allows us to feel pleasant touch sensation can switch function and instead signal pain after nerve damage. The results, which are presented in the journal Science, can eventually lead to more effective pain treatments.
Severe, treatment-demanding chronic nerve pain is a common condition but the drugs available have, at best, only some efficacy. Since the mechanisms behind nerve pain are largely unknown, the pharmaceutical industry has encountered major setbacks in the development of new drugs.
It was previously assumed that certain sensory neurons only transmit pleasant tactile sensations, while other specializes to transmit pain. During chronic nerve pain, normal touch can cause pain, but how this happens has remained a mystery. Scientists have now discovered that a small RNA molecule (microRNA) clusters in sensory neurons regulates how touch is perceived. Upon nerve damage, levels of this molecule drop in the sensory neurons, which results in raised levels of a specific ion channel that makes the nerve cells sensitive to pain.
"Our study shows that touch-sensitive nerves switch function and start producing pain, which can explain how hypersensitivity arises," says the senior author. "MicroRNA regulation could also explain why people have such different pain thresholds."
A single cluster controls more than 80% of neuropathic pain–regulated genes and scales basal mechanical sensitivity and mechanical allodynia by regulating auxiliary voltage-gated calcium channel subunits α2δ-1 and α2δ-2. Basal sensitivity is controlled in nociceptors, and allodynia involves TrkB+ light-touch mechanoreceptors.
These light-touch–sensitive neurons, which normally do not elicit pain, produce pain during neuropathy that is reversed by gabapentin. The drug substance gabapentin is often used to treat nerve pain, even though the mechanism of action has not been known. The new study shows that gabapentin operates in the touch-sensitive neurons and blocks the ion channel that increases when microRNA levels decrease. Yet it is still around only half of all patients who respond positively to the treatment.
The research was primarily conducted on mice but also verified in tests on human tissue, where low microRNA levels could be linked to high levels of the specific ion channel and vice versa, suggesting that the mechanism is the same in humans.
"It's vital that we understand the mechanisms that lead to chronic nerve pain so that we can discover new methods of treatment," says senior author. "The pharmaceutical companies have concentrated heavily on substances that target ion channels and receptors in pain neurons, but our results show that they might have been focusing on the wrong type of neuron."
http://ki.se/en/news/unexpected-mechanism-behind-chronic-nerve-pain
http://science.sciencemag.org/content/early/2017/05/31/science.aam7671
Latest News
More influence of environme…
By newseditor
Posted 24 Apr
The assembly of the human c…
By newseditor
Posted 24 Apr
Wiring of the human neocortex
By newseditor
Posted 24 Apr
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Other Top Stories
Copper is key in burning fat
Read more
How altered gut microbes cause obesity
Read more
Receptor in nasal cavity may be linked to preference for high-fat food
Read more
Signaling molecules can make neuronal extensions retract at a distance
Read more
Hunger' neurons in the brain are regulated by protein activated dur…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Distinct genetic and enviro…
By newseditor
Posted 24 Apr
Hippocampus-to-amygdala pat…
By newseditor
Posted 24 Apr
Integrative spatial analysi…
By newseditor
Posted 24 Apr
Time-series reconstruction…
By newseditor
Posted 24 Apr
Harnessing gastrointestinal…
By newseditor
Posted 24 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar