OT: chronic pain--new approach--U. of T.

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U of T researcher discovers way to zip away chronic pain

Peptide inhibitor called ZIP may be instrumental

http://www.news.utoronto.ca/lead-stories/u-of-t-researcher-discovers-way-to-zip-\

away-chronic-pain.html

By Cantin, posted Friday, December 3, 2010

Research from the University of Toronto suggests that a peptide inhibitor called

ZIP could be crucial in zipping away some kinds of chronic pain.

The new research, led by Professor Min Zhuo of the University of Toronto's

Department of Physiology and published in the current edition of the journal

Science, explores the role that the protein kinase M zeta (PKM?) plays in

storing " memories " of pain and therefore enhancing the sensation of pain.

Blocking the effect of PKM? through the use of a selective inhibitor called

?-pseudosubstrate inhibitory peptide - or ZIP -- blocked behavioral

sensitization and nerve injury related to chronic pain.

Normal pain or physiological pain is an important warning signal to avoid

potentially dangerous situations or environments. It is brief, and

short-lasting. Chronic pain is different, as it persists for weeks, month or

years due to spontaneous firing or overexcited pain-related neurons.

" What makes chronic pain difficult to treat is that these painful signals

trigger long-term plastic changes in different cortical areas and form permanent

bad 'memory'. It explains why the treatment of chronic pain in areas like the

spinal cord is often insufficient or ineffective, " said Zhuo, the Canada

Research Chair in Pain and Cognition.

Most previous studies have focused on signalling proteins that trigger these

plastic changes, while few have addressed the maintenance of plastic changes

related to chronic pain. Zhuo and his colleagues, Professors Bong-Kiun Kaang at

the Seoul National University and Graham Collingridge in Bristol University,

turned to PKM? because of its well-established role as a memory storage molecule

in two areas of the brain crucial for sensory and taste memory - the hippocampus

and the neocortex.

The forebrain region known as the anterior cingulate cortex (ACC) is a centre of

a different form of pain - chronic pain or psychogenic (social) pain. Zhuo calls

ACC the area where we experience " the unpleasantness of pain. "

" Injury caused by peripheral inflammation, nerve ligation or amputation causes

long-term enhancement of neuronal activity in the ACC. However, the question of

what molecule maintains these painful changes has been unclear, " he said.

Zhuo and his collaborators found that PKM? was indeed activated in the ACC when

subjects were experiencing peripheral nerve injury. That suggests that PKM? can

be a therapeutic target for the treatment of pain, and the use of ZIP

successfully muted chronic pain.

" This finding opens up a new area for pain researchers, and our hope is it will

yield new strategies to assist people who struggle daily with the challenges of

chronic pain, " Zhuo said.