New insight on inflammatory regulation could inform future pain drug development

December 18, 2018

A novel way in which the inflammatory response to pain is regulated has been described in the open-access journal eLife.

The results add to our understanding of the mechanisms that cause increased sensitivity to pain in response to injury and inflammation, and could pave the way for more effective therapies.

Inflammatory hyperalgesia, the hypersensitivity to thermal and chemical stimuli, can be divided into two phases - acute and chronic. As part of this condition, inflammatory mediators, including growth factors, stimulate and sensitise pain receptors. A protein that also plays a key role here is Transient Receptor Potential Vanilloid Subtype 1 (TRPV1).

Nerve growth factor (NGF) is also involved in inflammatory hyperalgesia and, in chronic pain, produces changes in the protein expression of TRPV1. "It has been known for over a decade that NGF sensitises pain-receptor neurons through increased trafficking of TRPV1 channels to the cell surface, and that this sensitisation requires the activation of an enzyme called phosphoinositide 3-kinase, or PI3K," explains first author Anastasiia Stratiievska, PhD candidate in the Department of Physiology and Biophysics at the University of Washington, Seattle, US. "But the mechanism by which this occurs was still unknown, and we wanted to gather more insights into the process."

To do this, Stratiievska and her team used an imaging technique called two-colour total internal reflection fluorescence microscopy to study TRPV1-expressing cells. Their analysis revealed that TRPV1 increased PI3K activity. Although TRPV1 is a large, multi-domain protein embedded in the cell surface, a small fragment of the protein called the ARD was enough to cause this increase in activity.

"Because the ARD is structurally conserved among TRPV channels, we tested whether other channels besides TRPV1 could increase NGF-induced PI3K activity," says senior author Sharona Gordon, Professor of Physiology and Biophysics at the University of Washington, Seattle. "We saw that this was indeed also true for TRPV2 and TRPV4."

"Together, our findings reveal a previously unknown reciprocal regulation among multiple TRPV channels and PI3K," Stratiievska concludes. "The next steps will be to identify ARD mutations that prevent this regulation. It would also be interesting to determine the exact role that reciprocal regulation plays in sensitisation to painful stimuli within model organisms, as this could help with the development of more effective painkillers further down the line."

The paper 'Reciprocal regulation among TRPV1 channels and phosphoinositide 3-kinase in response to nerve growth factor' can be freely accessed online at Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
01223 855373

About eLife

eLife aims to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Biochemistry and Chemical Biology, and Structural Biology and Molecular Biophysics, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open-source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at

To read the latest Biochemistry and Chemical Biology research published in eLife, visit

For our latest Structural Biology and Molecular Biophysics research, visit


Related Pain Articles from Brightsurf:

Pain researchers get a common language to describe pain
Pain researchers around the world have agreed to classify pain in the mouth, jaw and face according to the same system.

It's not just a pain in the head -- facial pain can be a symptom of headaches too
A new study finds that up to 10% of people with headaches also have facial pain.

New opioid speeds up recovery without increasing pain sensitivity or risk of chronic pain
A new type of non-addictive opioid developed by researchers at Tulane University and the Southeast Louisiana Veterans Health Care System accelerates recovery time from pain compared to morphine without increasing pain sensitivity, according to a new study published in the Journal of Neuroinflammation.

The insular cortex processes pain and drives learning from pain
Neuroscientists at EPFL have discovered an area of the brain, the insular cortex, that processes painful experiences and thereby drives learning from aversive events.

Pain, pain go away: new tools improve students' experience of school-based vaccines
Researchers at the University of Toronto and The Hospital for Sick Children (SickKids) have teamed up with educators, public health practitioners and grade seven students in Ontario to develop and implement a new approach to delivering school-based vaccines that improves student experience.

Pain sensitization increases risk of persistent knee pain
Becoming more sensitive to pain, or pain sensitization, is an important risk factor for developing persistent knee pain in osteoarthritis (OA), according to a new study by researchers from the Université de Montréal (UdeM) School of Rehabilitation and Hôpital Maisonneuve Rosemont Research Centre (CRHMR) in collaboration with researchers at Boston University School of Medicine (BUSM).

Becoming more sensitive to pain increases the risk of knee pain not going away
A new study by researchers in Montreal and Boston looks at the role that pain plays in osteoarthritis, a disease that affects over 300 million adults worldwide.

Pain disruption therapy treats source of chronic back pain
People with treatment-resistant back pain may get significant and lasting relief with dorsal root ganglion (DRG) stimulation therapy, an innovative treatment that short-circuits pain, suggests a study presented at the ANESTHESIOLOGY® 2018 annual meeting.

Sugar pills relieve pain for chronic pain patients
Someday doctors may prescribe sugar pills for certain chronic pain patients based on their brain anatomy and psychology.

Peripheral nerve block provides some with long-lasting pain relief for severe facial pain
A new study has shown that use of peripheral nerve blocks in the treatment of Trigeminal Neuralgia (TGN) may produce long-term pain relief.

Read More: Pain News and Pain Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to