Featured Research

from universities, journals, and other organizations

A Step Forward In Targeted Pain Therapy

Date:
January 24, 2008
Source:
Swiss Federal Institute of Technology Zurich
Summary:
Our bodies sense painful stimuli through certain receptors located in the skin, in joints and many internal organs. Specialized nerve fibers relay these signals coming from the periphery to the brain, where pain becomes conscious. The spinal cord is placed between these structures as kind of a pain filter. That filter assures that pain is not evoked by everyday stimuli like a light touch.

Diagram showing the pathway of pain from a joint to the brain. Pharmacological enhancement of spinal GABA receptor function inhibits the relay of pain signals to the brain.
Credit: Image courtesy of Swiss Federal Institute of Technology Zurich

Our bodies sense painful stimuli through certain receptors located in the skin, in joints and many internal organs. Specialized nerve fibers relay these signals coming from the periphery to the brain, where pain becomes conscious. “The spinal cord is placed between these structures as kind of a pain filter”, says Hanns Ulrich Zeilhofer, Professor at the Institute of Pharmaceutical Sciences at ETH Zurich and at the Institute of Pharmacology and Toxicology of the University of Zurich.

Related Articles


That filter assures that pain is not evoked by everyday stimuli like light touch. This is accomplished by inhibitory nerve cells located in the spinal dorsal horn that release the messenger molecule-amino butyric acid (GABA) at specialized contacts between neighboring nerve cells, so-called synapses. GABA then activates chloride channels on those neighboring cells which relay the pain signals to the brain.

Activating pain inhibiting factors

In patients with chronic inflammatory diseases, such as rheumatoid arthritis or after nerve damage, for example following injuries, the pain inhibiting action of GABA becomes severely compromised. Pain signals are then conducted to the brain nearly unfiltered. Benzodiazepines, such as the sedative drug Valiumฎ, which enhance the action of GABA, alleviate chronic pain when they are applied directly to the spinal cord via an injection into the spinal canal. In practice, however, such injections can only be done in very selected cases.

More often benzodiazepines are administered systemically, such as with tablets. In this instance, the benzodiazepines not only act in the spinal cord but also in the brain where they can have undesired, sometimes deleterious, effects on pain patients. The drugs cause sedation, impair memory, and can even lead to addiction. In addition, during prolonged treatment their effect often fades with time. Classic benzodiazepines should therefore be avoided in chronic pain patients.

GABAA receptors as pain targets

It had been acknowledged for some time that GABA serves important functions in pain control. That benzodiazepines act on at least four different subtypes of GABA receptors was also known. Nonetheless, these receptors were largely neglected as potential targets for pain treatment.

The research team led by Ulrich Zeilhofer used genetically altered mice in experiments to target the GABA receptors that control spinal pain relay. They first induced a slight inflammation in one hind paw or irritated the sciatic nerve to induce pain. A few days later the mice received an injection of a benzodiazepine close to the spinal cord. Experiments with the mice allowed the researchers to identify two subtypes of GABAA receptors which mediate spinal pain control.

A challenge for drug design

For experiments with animals, drugs with the proposed receptor specificity are already available. Such experiments have confirmed that the pharmacological enhancement of spinal GABA receptor function inhibits the relay of pain signals to the brain. Further studies have also shown that these compounds did not lose their analgesic effects during prolonged treatment and did not lead to addiction.

Successful design of a drug that targets only those two subtypes of GABA receptors would be a big step forward in pain therapy. Chronic pain could be treated specifically and with fewer side effects. “The challenge is now for pharmaceutical companies to develop drugs that specifically target these receptors in humans”, says Zeilhofer.

Journal reference: "Reversal of pathological pain through specific spinal GABAA receptor subtypes" , Julia Knabl, Robert Witschi, Katharina H๖sl, Heiko Reinold, Ulrike B. Zeilhofer, Seifollah Ahmadi, Johannes Brockhaus, Marina Sergejeva, Andreas Hess, Kay Brune, Jean-Marc Fritschy, Uwe Rudolph, Hanns M๖hler & Hanns Ulrich Zeilhofer, Nature, Vol 451, 17 January 2008


Story Source:

The above story is based on materials provided by Swiss Federal Institute of Technology Zurich. Note: Materials may be edited for content and length.


Cite This Page:

Swiss Federal Institute of Technology Zurich. "A Step Forward In Targeted Pain Therapy." ScienceDaily. ScienceDaily, 24 January 2008. <www.sciencedaily.com/releases/2008/01/080121120828.htm>.
Swiss Federal Institute of Technology Zurich. (2008, January 24). A Step Forward In Targeted Pain Therapy. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2008/01/080121120828.htm
Swiss Federal Institute of Technology Zurich. "A Step Forward In Targeted Pain Therapy." ScienceDaily. www.sciencedaily.com/releases/2008/01/080121120828.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) — Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins