Nav: Home

Pain neuron may protect fungal inflammation and bone destruction

June 29, 2017

Pain neuron exaggerates inflammation of contact dermatitis and psoriasis. Despite its importance in allergic and autoimmune inflammation, it is not known so far whether pain neuron modulates pathogen-induced inflammation. Scientist at Immunology Frontier Research Center (IFReC) discovered that Nav1.8 ion channel expressing pain neuron inhibits fungal inflammation and bone destruction.

"We generated the Nav1.8 ion channel expressing neuron null mice. After C. albicans or C. albicans derived β-glucan injection into the hind paw, these mice showed significantly increased footpad swelling and bone destruction" said Kenta Maruyama, M.D., Ph.D. (Assistant Professor, IFReC). Intriguingly, Nav1.8 ion channel positive neuron expresses Dectin-1, a β-glucan receptor, and Dectin-1 mediated inflammation is potently suppressed by pain neurons, rather than bacterial component-induced inflammation. Detailed experiments of pain neurons revealed that Dectin-1-stumulated pain neuron produces robust amount of CGRP, a neuropeptide that inhibits osteoclast and cytokine production via TRPV1 and TPRA1 ion channel activation. "To our surprise, TRPV1/TRPA1 double deficient mice exhibited exaggerated inflammation and bone destruction in response to β-glucan due to impaired CGRP production, and myeloid cell transcription factor Jdp2 is necessary for the immunosuppression triggered by this neuropeptide" said Kenta.

A significant discovery in this study is that transcription factor Jdp2 is induced by CGRP and directly inhibits β-glucan-indeuced NF-κB activation in macrophages. Such findings are consistent with the results showing that Jdp2 deficiency hyper inflammatory phenotype induced by β-glucan was only observed in vivo.

Additional study revealed that β-glucan-induced CGRP production from pain neuron is more potent than that induced by LPS, a gram negative bacterial component.

"Previous reports suggested that pain neurons are deleterious for inflammation, but our findings suggest that pain neurons may function primarily in suppressing fungal inflammation, rather than bacterial inflammation" said Kenta. "Congenital insensitivity to pain with anhidrosis is an extremely rare hereditary disease characterized by impairment of nociceptor development. Manifestations of this disease are recurrent episodes of skin injury, osteomyelitis, bony fractures, and oral osteolysis. Our discovery may improve the therapeutic strategies of this disease and precise microbiological observation of this patient may clarify the bona-fide role of human pain neurons in fungal infection."
-end-


Osaka University

Related Inflammation Articles:

TWEAKing inflammation
Superficially, psoriasis and atopic dermatitis may appear similar but their commonalities are only skin deep.
More than a 'gut feeling' on cause of age-associated inflammation
Bowdish and her colleagues raised mice in germ-free conditions and compared them to their conventionally raised counterparts.
Inflammation: It takes two to tango
Signal molecules called chemokines often work in tandem to recruit specific sets of immune cells to sites of tissue damage.
Inflammation awakens sleepers
The inflammatory response that is supposed to ward off pathogens that cause intestinal disease makes this even worse.
Inflammation in regeneration: A friend or foe?
Scientists at Tokyo Institute of Technology have discovered a novel mechanism linking inflammation and organ regeneration in fish, which can be conserved among vertebrates.
More Inflammation News and Inflammation Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...