Media Releases

U of T researcher discovers a way to zip away chronic pain

December 2, 2010

TORONTO, ON — 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 Prof. Min Zhuo of the Uni­ver­si­ty of Toronto’s Depart­ment of Phys­i­ol­o­gy and pub­lished under the title “Alle­vi­at­ing Neu­ro­path­ic Pain Hyper­sen­si­tiv­i­ty by Inhibit­ing PKMζ in the Ante­ri­or Cin­gu­late Cor­tex” in the cur­rent edi­tion of the jour­nal Sci­ence, explores the role that the pro­tein kinase M zeta (PKMζ) plays in stor­ing “mem­o­ries” of pain and there­fore enhanc­ing the sen­sa­tion of pain. Block­ing the effect of PKMζ  through the use of a selec­tive inhibitor called ζ‑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 Prof. Zhuo, the Cana­da Research Chair in Pain and Cog­ni­tion.

Most pre­vi­ous stud­ies have focused on sig­nal­ing pro­teins that trig­ger these plas­tic changes, while few have addressed the main­te­nance of plas­tic changes relat­ed to chron­ic pain.  Prof. Zhuo and his col­leagues, Prof. Bong-Kiun Kaang at the Seoul Nation­al Uni­ver­si­ty and Gra­ham Collingridge in Bris­tol Uni­ver­si­ty, turned to PKMζ  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. Prof. 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.

Prof. Zhuo and his col­lab­o­ra­tors found that PKMζ was indeed acti­vat­ed in the ACC when sub­jects were expe­ri­enc­ing periph­er­al nerve injury. That sug­gests that PKMζ 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,” Prof. Zhuo said.


For more infor­ma­tion, please con­tact:

Paul Can­tin
Asso­ciate Direc­tor
Strate­gic Com­mu­ni­ca­tions
Uni­ver­si­ty of Toron­to Temer­ty Temer­ty Fac­ul­ty of Med­i­cine
ph: 416–978-2890