Media Releases

U of T researchers discover asphyxia trigger in opioid poisoning

January 26, 2011

TORONTO, ON – Researchers at the Uni­ver­si­ty of Toron­to have dis­cov­ered a new way to com­bat asphyx­i­a­tion caused by opi­oid poi­son­ing, by “res­cu­ing” a part of the brain which con­trols breath­ing. Hav­ing deter­mined the mech­a­nism of action of opi­ate sup­pres­sion of breath­ing, the effec­tive­ness of a com­mon­ly-used drug like nalox­one pro­vides a tar­get for fur­ther drug devel­op­ment.

In a paper pub­lished today in the Jour­nal of Neu­ro­science, a team includ­ing researchers from the Uni­ver­si­ty of Toron­to and the Uni­ver­si­ty of Alber­ta, say they have iden­ti­fied a poten­tial means to com­bat the grow­ing prob­lem of opi­oid poi­son­ing result­ing in asphyx­ia.

Opi­ates are among the old­est known drugs in the world, with recog­ni­tion of their ben­e­fi­cial effects (espe­cial­ly the anal­gesic – painkilling – prop­er­ties) and ther­a­peu­tic use pre­dat­ing record­ed his­to­ry. Through­out the cen­turies, how­ev­er, the dark side to these drugs has also been well rec­og­nized: opi­oid drugs have addic­tive poten­tial and they have tox­ic side effects. Accord­ing to the U.S. Cen­ters for Dis­ease Con­trol and Pre­ven­tion, opi­oid anal­gesics are involved in about 40% of all poi­son­ing deaths in North Amer­i­ca. Deaths relat­ed to opi­oid drugs are increas­ing in Cana­da. In 2009, the Cana­di­an Med­ical Asso­ci­a­tion Jour­nal report­ed that in Ontario, there has been a two-fold increase in opi­oid-relat­ed deaths over the last 16 years, since the intro­duc­tion of long-act­ing oxy­codone to the provin­cial drug for­mu­la­ry.

“Asphyx­ia caused by severe under-breath­ing and ‘res­pi­ra­to­ry arrest’ is the most seri­ous side effect pro­duced by opi­oids. For cen­turies how­ev­er, the crit­i­cal site in the brain where opi­oid drugs crit­i­cal­ly affect breath­ing was not known,” said Prof. Richard Horner, of the Depart­ment of Med­i­cine, Depart­ment of Phys­i­ol­o­gy and the Cana­da Research Chair in Sleep and Res­pi­ra­to­ry Neu­ro­bi­ol­o­gy.

In the arti­cle, enti­tled “Pre-Bötzinger com­plex neurokinin‑1 recep­tor-express­ing neu­rons medi­ate opi­oid-induced res­pi­ra­to­ry depres­sion,” Prof. Horner with Gas­pard Mon­tan­don and their col­leagues deter­mined that a small col­lec­tion of cells with­in the medul­la oblon­ga­ta – the sec­tion of the brain which con­trols vital bod­i­ly func­tions – is crit­i­cal for main­tain­ing breath­ing, but also sen­si­tive to opi­oids. This region, known as the pre-Bötzinger Com­plex, can trig­ger asphyx­ia under the influ­ence of opi­oids.

The cells in this region of the medul­la oblon­ga­ta that are affect­ed by opi­oids have a chem­i­cal con­sti­tu­tion that is dis­tinct from oth­er cells in this region. The goal is to specif­i­cal­ly tar­get these cells to reac­ti­vate them in the pres­ence of opi­oids. Such a strat­e­gy would pre­serve the ben­e­fi­cial painkilling prop­er­ties of these drugs but pre­vent the poten­tial­ly lethal side effect of res­pi­ra­to­ry arrest.

“The good news is our research demon­strat­ed that the res­pi­ra­to­ry dis­tress can be res­cued by the intro­duc­tion of the drug nalox­one, which revers­es the effects of opi­oids,” Prof. Horner says. “These find­ings are essen­tial to devel­op new phar­ma­co­log­i­cal approach­es to pre­vent life-threat­en­ing res­pi­ra­to­ry depres­sion, with­out reduc­ing the ben­e­fi­cial anal­gesic prop­er­ties of opi­oid drugs.”

Col­lab­o­rat­ing Teams:
Uni­ver­si­ty of Toron­to: Gas­pard Mon­tan­don, Richard Horner,
Hat­tie Liu
Uni­ver­si­ty of Alber­ta: Wux­u­an Qin, Jun Ren, John Greer

Fund­ing for this Research:
Cana­di­an Insti­tutes of Health Research (CIHR) to Richard L. Horner; Ontario Tho­racic Soci­ety, Cana­di­an Lung Asso­ci­a­tion to Richard L. Horner; Ontario Tho­racic Soci­ety, Cana­di­an Lung Asso­ci­a­tion Fel­low­ship to Gas­pard Mon­tan­don; Cana­di­an Insti­tutes of Health Research (CIHR) to John J. Greer.


To speak to Prof. Horner, please con­tact:

Jen­nifer Lit­tle
Senior Com­mu­ni­ca­tions Offi­cer
Temer­ty Temer­ty Fac­ul­ty of Med­i­cine, Uni­ver­si­ty of Toron­to
phone: 416–946-8423