Navigation Links
The pain puzzle: Uncovering how morphine increases pain in some people
Date:1/6/2013

Quebec City & Toronto, January 6, 2013For individuals with agonizing pain, it is a cruel blow when the gold-standard medication actually causes more pain. Adults and children whose pain gets worse when treated with morphine may be closer to a solution, based on research published in the January 6 on-line edition of Nature Neuroscience.

"Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients," says senior author Dr. Yves De Koninck, Professor at Universit Laval in Quebec City. The team included researchers from The Hospital for Sick Children (SickKids) in Toronto, the Institut universitaire en sant mentale de Qubec, the US and Italy.

New pathway in pain management

The research not only identifies a target pathway to suppress morphine-induced pain but teases apart the pain hypersensitivity caused by morphine from tolerance to morphine, two phenomena previously considered to be caused by the same mechanisms.

"When morphine doesn't reduce pain adequately the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known. But sometimes increasing the morphine can, paradoxically, makes the pain worse," explains co-author Dr. Michael Salter. Dr. Salter is Senior Scientist and Head of Neurosciences & Mental Health at SickKids, Professor of Physiology at University of Toronto, and Canada Research Chair in Neuroplasticity and Pain.

"Pain experts have thought tolerance and hypersensitivity (or hyperalgesia) are simply different reflections of the same response," says Dr. De Koninck, "but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain."

Dr. Salter adds, "We identified specialized cells known as microglia in the spinal cord as the culprit behind morphine-induced pain hypersensitivity. When morphine acts on certain receptors in microglia, it triggers the cascade of events that ultimately increase, rather than decrease, activity of the pain-transmitting nerve cells."

The researchers also identified the molecule responsible for this side effect of morphine. "It's a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain," explains Dr. De Koninck. "Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity." Dr. De Koninck and researchers at Universit Laval are testing new molecules capable of preserving KCC2 functions and thus preventing hyperalgesia.

The KCC2 pathway appears to apply to short-term as well as to long-term morphine administration, says Dr. De Koninck. "Thus, we have the foundation for new strategies to improve the treatment of post-operative as well as chronic pain."

Dr. Salter adds, "Our discovery could have a major impact on individuals with various types of intractable pain, such as that associated with cancer or nerve damage, who have stopped morphine or other opiate medications because of pain hypersensitivity."

Cost of pain

Pain has been labelled the silent health crisis, afflicting tens of millions of people worldwide. Pain has a profound negative effect on the quality of human life. Pain affects nearly all aspects of human existence, with untreated or under-treated pain being the most common cause of disability. The Canadian Pain Society estimates that chronic pain affects at least one in five Canadians and costs Canada $55-60 billion per year, including health care expenses and lost productivity.

"People with incapacitating pain may be left with no alternatives when our most powerful medications intensify their suffering," says Dr. De Koninck, who is also Director of Cellular and Molecular Neuroscience at Institut universitaire en sant mentale de Qubec.

Dr. Salter adds, "Pain interferes with many aspects of an individual's life. Too often, patients with chronic pain feel abandoned and stigmatized. Among the many burdens on individuals and their families, chronic pain is linked to increased risk of suicide. The burden of chronic pain affects children and teens as well as adults." These risks affect individuals with many types of pain, ranging from migraine and carpel-tunnel syndrome to cancer, AIDS, diabetes, traumatic injuries, Parkinson's disease and dozens of other conditions.


'/>"/>

Contact: Jean-Franois Hupp
jean-francois.huppe@dc.ulaval.ca
418-656-7785
Universit Laval
Source:Eurekalert

Related biology news :

1. New method for uncovering side effects before a drug hits the market
2. Uncovering the genomes regulatory code
3. Bedroom TV viewing increases risk of obesity in children
4. Second-hand smoke increases risk of invasive meningococcal disease in children
5. OHSU study shows that a molecule critical to nerve cells increases drammatically during hypertension
6. Cell Transplantation reports islet cell advancement increases impact on transplantation
7. Climate change increases stress, need for restoration on grazed public lands
8. Chronic kidney disease increases risk of death at all ages
9. HIV treatment use increases in the US
10. Westlake Chemical Increases Quarterly Dividend By Over 150%
11. How chronic obstructive pulmonary disease increases risk of lung cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/3/2016)... 2016 --> ... "Automated Fingerprint Identification System Market by Component (Hardware and ... & Finance, Government, Healthcare, and Transportation) and Geography - ... is expected to be worth USD 8.49 Billion by ... and 2020. The transformation and technology evolution from the ...
(Date:2/2/2016)... , Feb. 2, 2016 This BCC ... bioinformatic market by reviewing the recent advances in ... that drive the field forward. Includes forecast through ... Identify the challenges and opportunities that exist in ... software solution developers, as well as IT and ...
(Date:2/2/2016)... Feb. 2, 2016  Based on its recent ... Sullivan recognizes US-based Intelligent Retinal Imaging Systems (IRIS) ... Award for New Product Innovation. IRIS, a prominent ... North America , is poised to set ... diabetic retinopathy market. The IRIS technology presents superior ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... VANCOUVER, British Columbia and MENLO PARK, ... Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical ... therapies, today announced that it will present at the ... on Monday, February 8, 2016 at 10:00 a.m. EST in ... Jeffrey Bacha , DelMar,s president and CEO, will provide an ...
(Date:2/4/2016)... ... February 04, 2016 , ... Franz Inc. , an ... technology has been recognized As “ Best in Semantic Web Technology - USA ... Corporate America, it’s our priority to showcase prominent professionals who are excelling in ...
(Date:2/3/2016)... -- With the growing need for better therapeutics, and ... such as monoclonal antibodies, recombinant protein therapeutics and ... are in high demand. Conventionally expression systems were ... of these therapeutics. However, due to issues with ... approaches and novel expression systems are currently being ...
(Date:2/3/2016)... ... February 03, 2016 , ... ... of potential targets (epitopes) specific to misfolded, propagating strains of Amyloid beta involved ... monoclonal antibody therapeutics for Alzheimer’s. , Following on from the first misfolded Amyloid ...
Breaking Biology Technology: