Researchers Identify Specific Targets For Pain Therapy - Professor Hanns Ulrich Zeilhofer: "The Challenge Is Now For Pharmaceutical Companies"

Main Category: Pain / Anesthetics
Article Date: 20 May 2008 - 3:00 PDT

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Researchers in Zurich, Switzerland have identified specific targets for the therapy of patients suffering from chronic pain. In experiments using mice, they succeeded in specifically blocking the relay of pain signals from the spinal cord to the brain. As a result, they were able to restore the body's pain filter in the spinal cord, which ensures that not every sensation, such as light touch, is registered as pain. Professor Hanns Ulrich Zeilhofer who works at the University of Zurich and at the Swiss Federal Institute of Technology (ETH) reported about these findings on May 16, 2008 at an international conference on the "Development and function of somatosensation and pain" organized by the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany. The challenge is now for pharmaceutical companies to develop drugs that specifically target these receptors in humans", he said.

Inflammatory diseases, such as rheumatoid arthritis or nerve damage, are frequently accompanied by severe and debilitating pain, which can become chronic. Patients suffering from chronic pain, for example, experience even a light touch as painful. Often they also suffer from sudden and very strong pain attacks. "The underlying cause for pain in chronic pain patients is quite often due to the loss of the filter function of inhibitory nerve cells", said Professor Zeilhofer.

Normally, these inhibitory nerve cells with their messenger molecule GABA block pain signals from the periphery to the brain and, therefore, prevent an individual from abnormally feeling pain in cases of light touch or sensation. GABA activates GABA-A receptors (chloride channels) in the neighbouring nerve cells and, thus, stops the relay to the brain. In chronic pain patients or patients with inflammatory diseases, the function of both GABA and another messenger molecule, glycin, is impaired.

"A class of drugs, benzodiazepines, can enforce GABA´s inhibitory effects in the nervous system. When injected directly into the spinal cord, these drugs also enforce the body's own pain inhibitory properties", Professor Zeilhofer explained. He continued: "Only in a few rare cases should such injections be administered into the spinal cord as chronic pain therapy. However, if benzodiazepines are given as pills, they cause many unpleasant side effects to the brain, such as fatigue and impairment of memory. Over time, these drugs also loose their effectiveness and, almost disturbingly, can lead to addiction. Therefore, classical benzodiazepines cannot be used for pain therapy", the pharmacologist said.

It has been known for quite some time that at least four different subtypes of the GABA receptor act on benzodiazepines. In experiments with genetically altered mice, Professor Zeilhofer and his colleagues were able to identify two subtypes of the GABA receptor, alpha 2 and alpha 3, which are directly involved in pain control. The researchers have already tested various chemicals in animal experiments which specifically activate these two GABA subtypes and effectively inhibit the relay of pain signals to the brain without causing the side effects associated with classical benzodiazepines.

Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch