Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Ouch! The receptors mediating acidic pain sensation

22.10.2002


When we feel pain in response to harmful stimuli it is the result of messages sent from pain sensors in the periphery of the body to the brain. These pain sensors – or nociceptors – often lie beneath the skin and detect and signal the presence of tissue-damaging stimuli or the existence of tissue damage. One particular nociceptor, vanilloid receptor-1 (VR1), relays sensory messages to the brain in response to thermal and painful chemical stimuli and is generally regarded as the major pain sensor.



In conditions such as arthritis or infection, the tissue involved at these sites becomes acidic. While normal human tissue has a neutral pH of approximately 6.5 - 7.5 (similar to water), tissue acidosis can cause a drop in cellular pH below 6.0 closer to that of household vinegar. When the cellular environment becomes acidic, both VR1 and a second nociceptor - acid sensing ion channels (ASICs) - are activated. In previous experiments in mice, scientists have found that the activation of VR1 requires extremely severe acidification - pH less than 6.0. This suggests that another pain sensor plays a role in nociception, specifically at pH levels greater than 6.0. Despite experimental data revealing that mouse neurons lacking ASICs are severely deficient in their responses to acidic stimuli, controversy remains about the function of ASICs in mammals.

In a study reported in the October 21 issue of the Journal of Clinical Investigation (JCI) by Shinya Ugawa and colleagues from the Nagoya City University Medical School, Japan, the authors demonstrated that both VR1 and ASICs are involved in the sensing of acid-evoked pain in humans and that each type of nociceptor mediates this pain perception at very specific pH ranges. The authors infused solutions of varying pH levels under the skin of the underside of the upper forearm of healthy male volunteers who were subsequently asked to estimate the intensity of the induced pain on a 0-10 scale. To determine which particular nociceptor was activated at each pH level, the authors systematically blocked ASICs-mediated pain perception with the ASICs inhibitor amiloride or VR1-mediated pain perception with the VR1-inhibitor capsazepine and then recorded the intensity of pain indicated by the subject in response to the solutions of various pH. Ugawa and colleagues found that amiloride potently blocked pain induced by solutions with a pH greater than 6.0, while capsazepine did not. At pH levels below 5.0, amiloride was less effective in reducing pain and capsazepine had a partial blocking effect.


These results demonstrated that ASICs, and not VR1, function as acid sensors within the pathophysiologically relevant pH range 6.0 – 7.2, and that the ASICs inhibitor amiloride may be a useful analgesic for the treatment of localized pain within this range.


CONTACT:

Shinya Ugawa
Department of Anatomy II
Nagoya City University Medical School
1 Kawasumi, Mizuho-cho,
Mizuho-ku, Nagoya 467-8601
JAPAN
TEL: 81-52-853-8126
FAX: 81-52-852-8887
E-mail: ugawa@med.nagoya-cu.ac.jp

Brooke Grindlinger, PhD | EurekAlert!
Further information:
http://www.jci.org/

More articles from Health and Medicine:

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

nachricht Highly precise wiring in the Cerebral Cortex
21.09.2017 | Max-Planck-Institut für Hirnforschung

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>