Dectin-1-mediated pain is critical for the resolution of fungal inflammation

August 29, 2018

Osaka, Japan - Candida albicans infection (candidiasis) can cause skin, genital, or oral pain. Many studies have attempted to understand the source of pain in candidiasis; none have provided a clear explanation, until now.

In a new study published in iScience, "The ATP transporter VNUT mediates induction of Dectin-1-triggered Candida nociception," a research team led by experts from Osaka University investigated the role of Dectin-1, a β-glucan receptor, in the sensing of fungal infection. They found that Dectin-1 was critical for the onset of pain related to fungal infection.

Candidiasis is an infection that causes skin or oral pain in many individuals. It frequently occurs in patients who are immunocompromised or have poorly controlled diabetes. Additionally, it affects a large proportion of women, causing vulvovaginal pain in approximately 75% of women worldwide at some point in their lifetimes, and causing severe nipple pain in some lactating women. Despite a variety of efforts to understand the mechanisms of such severe pain in candidiasis, the primary effective treatment has been resolution of the infection, which does not occur quickly, particularly in immunocompromised patients.

"We previously found that fungal infection stimulated pain through β-glucan nociceptors, such as Dectin-1, but we did not know whether these receptors directly interacted with Candida fungi," says Kenta Maruyama, lead author on the study. "We were excited to find that β-glucan-induced pain is abolished in Dectin-1 and TRPV1/TRPA1 deficient mice."

In the study, the researchers found that β-glucan stimulates nociceptors via the Dectin-1-PLC axis, activating neurons. Notably, components secreted from fungal cells caused the same activation of nociceptors.

"Our analyses revealed that β-glucan-induced allodynia (pain) is dependent on extracellular ATP and VNUT, an ATP transporter," says Maruyama. "We found that the VNUT inhibitor clodronate can be used to treat β-glucan-induced allodynia."

In addition to identifying a mechanism to block fungal pain in mice, the researchers identified a new signaling pathway, from Dectin-1 to TRP channels in the generation of pain and found that the ultimate activation of such pain was critical for the resolution of fungal inflammation.

Candidiasis is a painful infection that affects a large number of individuals, and may cause extreme pain in some cases. This study has shown that the Dectin-1 pathway could be an important new target for treatment of candidiasis, and that clodronate may provide a readily available therapy that may be quickly used in clinical treatment of severe fungal pain.
-end-
The article, "The ATP transporter VNUT mediates induction of Dectin-1-triggered Candida nociception," was published in iScience, https://doi.org/10.1016/j.isci.2018.08.007.

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum. Website: http://resou.osaka-u.ac.jp/en/top

Osaka University

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
Brightsurf.com 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 Amazon.com.