Tag Archives: neuropathic pain

Café Scientifique (Vancouver, Canada) hosts ‘pain’ talk on Sept. 29, 2015

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The first Café Scientifique (Vancouver, Canada edition) event of the fall will feature a previously postponed (due to one of the speakers becoming a father) talk on pain.

On Tuesday, September 29, 2015  Café Scientifique, held in the back room of The Railway Club (2nd floor of 579 Dunsmuir St. [at Seymour St.]), will be hosting a talk on pain: the good and the bad (from the April 13, 2015 and Sept. 7, 2015 announcements),

Our speakers for the evening will be Dr. Matthew Ramer and Dr. John Kramer.  The title of their talk is:

Knowing Pains: How can we study pain to better treat it?

Pain is arguably the most useful of sensations.  It is nature’s way of telling us to stop doing whatever it is we are doing in order to prevent damage, and to protect injured body parts during the healing process.  In the absence of pain (in certain congenital conditions and in advanced diabetes, for example), the consequence can be loss of limbs and even of life.

There are circumstances, however, when pain serves no useful purpose:  it persists when the injury has healed or occurs in the absence of any frank tissue damage, and is inappropriate in context (previously innocuous stimuli become painful) and magnitude (mildly painful stimuli become excruciating).  This is called neuropathic pain and is incredibly difficult to treat because it is unresponsive to all of the drugs we use to treat normal, useful (“acute”) pain.

Ultimately, our research is aimed at finding new ways to minimise suffering from neuropathic pain.  Prerequisites to this goal include understanding how normal and neuropathic pain are encoded and perceived by the nervous system, and accurately measuring and quantifying pain so that we can draw reasonable conclusions about whether or not a particular treatment is effective.  We will discuss some historical and current ideas of how pain is transmitted from body to brain, and emphasize that the pain “channel” is not hard-wired, but like the process of learning, it is plastic, labile, and subject to “top-down” control.  We will also tackle the contentious issue of pain measurement in the clinic and laboratory.*

Both speakers are from iCORD (International Collaboration On Repair Discoveries), an interdisciplinary research centre focused on spinal cord injury located at Vancouver General Hospital. There’s more about Dr. Matt Ramer here and Dr. John Kramer here.

BTW, Dr. Kramer is the new father.

Pain in your blood—converting blood cells to neurons at McMaster University (Canada)

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Having once spent several months doing a literature search on pain and morphine, I have a particular interest in this breakthrough from McMaster University (Canada) announced in a May 21, 2015 news item on ScienceDaily,

Scientists at McMaster University have discovered how to make adult sensory neurons from human patients simply by having them roll up their sleeve and providing a blood sample.

Specifically, stem cell scientists at McMaster can now directly convert adult human blood cells to both central nervous system (brain and spinal cord) neurons as well as neurons in the peripheral nervous system (rest of the body) that are responsible for pain, temperature and itch perception. This means that how a person’s nervous system cells react and respond to stimuli, can be determined from his blood.

A May 21, 2015 McMaster University news release on EurekAlert, which originated the news item, describes why this will make a difference for pain management,

Currently, scientists and physicians have a limited understanding of the complex issue of pain and how to treat it. The peripheral nervous system is made up of different types of nerves – some are mechanical (feel pressure) and others detect temperature (heat). In extreme conditions, pain or numbness is perceived by the brain using signals sent by these peripheral nerves.

“The problem is that unlike blood, a skin sample or even a tissue biopsy, you can’t take a piece of a patient’s neural system. It runs like complex wiring throughout the body and portions cannot be sampled for study,” said Bhatia [Mick Bhatia, director of the McMaster Stem Cell and Cancer Research Institute and much more].

“Now we can take easy to obtain blood samples, and make the main cell types of neurological systems – the central nervous system and the peripheral nervous system – in a dish that is specialized for each patient,” said Bhatia. “Nobody has ever done this with adult blood. Ever.

“We can actually take a patient’s blood sample, as routinely performed in a doctor’s office, and with it we can produce one million sensory neurons, that make up the peripheral nerves in short order with this new approach. We can also make central nervous system cells, as the blood to neural conversion technology we developed creates neural stem cells during the process of conversion.”

His team’s revolutionary, patented direct conversion technology has “broad and immediate applications,” said Bhatia, adding that it allows researchers to start asking questions about understanding disease and improving treatments such as: Why is it that certain people feel pain versus numbness? Is this something genetic? Can the neuropathy that diabetic patients experience be mimicked in a dish?

It also paves the way for the discovery of new pain drugs that don’t just numb the perception of pain. Bhatia said non-specific opioids used for decades are still being used today.

“If I was a patient and I was feeling pain or experiencing neuropathy, the prized pain drug for me would target the peripheral nervous system neurons, but do nothing to the central nervous system, thus avoiding non-addictive drug side effects,” said Bhatia.

“You don’t want to feel sleepy or unaware, you just want your pain to go away. But, up until now, no one’s had the ability and required technology to actually test different drugs to find something that targets the peripheral nervous system and not the central nervous system in a patient specific, or personalized manner.”

Bhatia’s team successfully tested their process using fresh blood, but also cryopreserved (frozen) blood. Since blood samples are taken and frozen with many clinical trials, this allows them “almost a bit of a time machine” to go back and explore questions around pain or neuropathy to run tests on neurons created from blood samples of patients taken in past clinical trials where responses and outcomes have already been recorded”.

In the future, the process may have prognostic potential, explained Bhatia, in that one might be able to look at a patient with Type 2 Diabetes and predict whether they will experience neuropathy by running tests in the lab using their own neural cells derived from their blood sample.

“This bench to bedside research is very exciting and will have a major impact on the management of neurological diseases, particularly neuropathic pain,” said Akbar Panju, medical director of the Michael G. DeGroote Institute for Pain Research and Care, a clinician and professor of medicine.

“This research will help us understand the response of cells to different drugs and different stimulation responses, and allow us to provide individualized or personalized medical therapy for patients suffering with neuropathic pain.”

Here’s a link to and a citation for the paper,

Single Transcription Factor Conversion of Human Blood Fate to NPCs with CNS and PNS Developmental Capacity by Jong-Hee Lee, Ryan R. Mitchell, Jamie D. McNicol, Zoya Shapovalova, Sarah Laronde, Borko Tanasijevic, Chloe Milsom, Fanny Casado, Aline Fiebig-Comyn, Tony J. Collins, Karun K. Singh, and Mickie Bhatia.
Publication stage: In Press Corrected Proof Open Access DOI: http://dx.doi.org/10.1016/j.celrep.2015.04.056 Open access funded by the Author(s)

This is an open access paper. h/t Speaking Up For Science May 21, 2015 item

Three Vancouver (Canada) science events: Vancouver Public Library on April 27, 2015, Café Scientifique on April 28, 2015, and the Wall Exchange on May 26, 2015

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Monday, April 27, 2015, 7:00 pm – 8:30 pm is a combined bee/poetry event at the main branch of the Vancouver Public Library. From the Vancouver Public Library “Honey, Hives, and Poetry in the City” event page,

Celebrate National Poetry Month by investigating food and poetry as a means of cultural and social activism and community building. Featured will be:

  • Rachel Rose, Poet Laureate of Vancouver
  • A collaborative reading by scientist and author Mark L. Winston (Bee Time: Lessons from the Hive) and award winning poet Renee Sarojini Saklikar (Children of Air India)
  • Readings from author and poet Elee Kraljii Gardiner and the Thursdays Writing Collective.
  • Presentation and honey tasting with Hives for Humanity.

Location:

Address: 350 West Georgia St.
VancouverV6B 6B1

  • Phone:

Location Details: Alice MacKay Room, Lower Level

[ETA April 21, 2015 at 1000 PST: I’ve just embedded a video which launches a new year of Science Rap Academy (Tom McFadden) in my April 21, 2015 post titled: Please, don’t kill my hive! (a Science Rap Academy production).]

*Change of Speaker for April 28, 2015  Café Scientifique, see Café Scientifique (Vancouver, Canada) makes a ‘happy’ change: new speaker for April 28, 2015 posting.”*

The day after the bee/poetry event, Tuesday, April 28, 2015  Café Scientifique, held in the back room of The Railway Club (2nd floor of 579 Dunsmuir St. [at Seymour St.], will be hosting a talk on pain (from the April 13, 2015 announcement,

Our speakers for the evening will be Dr. Matthew Ramer and Dr. John Kramer.  The title of their talk is:

Knowing Pains: How can we study pain to better treat it?

Pain is arguably the most useful of sensations.  It is nature’s way of telling us to stop doing whatever it is we are doing in order to prevent damage, and to protect injured body parts during the healing process.  In the absence of pain (in certain congenital conditions and in advanced diabetes, for example), the consequence can be loss of limbs and even of life.

There are circumstances, however, when pain serves no useful purpose:  it persists when the injury has healed or occurs in the absence of any frank tissue damage, and is inappropriate in context (previously innocuous stimuli become painful) and magnitude (mildly painful stimuli become excruciating).  This is called neuropathic pain and is incredibly difficult to treat because it is unresponsive to all of the drugs we use to treat normal, useful (“acute”) pain.

Ultimately, our research is aimed at finding new ways to minimise suffering from neuropathic pain.  Prerequisites to this goal include understanding how normal and neuropathic pain are encoded and perceived by the nervous system, and accurately measuring and quantifying pain so that we can draw reasonable conclusions about whether or not a particular treatment is effective.  We will discuss some historical and current ideas of how pain is transmitted from body to brain, and emphasize that the pain “channel” is not hard-wired, but like the process of learning, it is plastic, labile, and subject to “top-down” control.  We will also tackle the contentious issue of pain measurement in the clinic and laboratory.*

Both speakers are from iCORD (International Collaboration On Repair Discoveries), an interdisciplinary research centre focused on spinal cord injury located at Vancouver General Hospital. There’s more about Dr. Matt Ramer here and Dr. John Kramer here.

*Change of Speaker for April 28, 2015  Café Scientifique, see Café Scientifique (Vancouver, Canada) makes a ‘happy’ change: new speaker for April 28, 2015 posting.”*

The Wall Institute for Advanced Studies is bringing Dr. Bonnie Bassler, the bacteria whisperer, to speak in Vancouver. From the Wall Exchange series event page,

Dr. Bonnie Bassler, Molecular Biology, Princeton University

The Secret Social Lives of Bacteria

May 26, 2015
7:30 pm. Doors open at 6:30 pm.
Vogue Theatre, 918 Granville Street, Vancouver

Tickets available online, 2015 or by calling the Vogue Theatre Box Office: 604-569-1144

Learn more:

Bacterial behaviour may hold key to combatting antibiotic resistance
The Wall Papers

Here are some more details about the tickets, the event, and the speaker from the Northern Tickets event page,

Bonnie Bassler
The Secret, Social Lives of Bacteria
Vogue Theatre
Tuesday May 26th, 2015
Doors 6:30PM, Begins 7:30PM
Free Entry
**Tickets must be redeemed by 7:15PM to be valid**

Dr. Bonnie Bassler is an investigator with the Howard Hughes Medical Institute and Squibb Professor and Chair of the Department of Molecular Biology at Princeton University. The research in Dr. Bassler’s laboratory focuses on the chemical signaling mechanisms that bacteria use to communicate with each other known as “quorum sensing.” Therapies that block quorum sensing activity may represent an important new strategy for combating bacterial infections. Her research reveals new insights into the basic biology and ecology of bacteria; findings that may have direct application in the future treatment of disease.
…
Vogue Theatre
918 Granville Street – Vancouver

Go forth and enjoy!

* Removed ‘,t’ at very end of Café Scientifique excerpt on April 24, 2015.

Growing new brain cells for implants

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The dream is that one day this research will allow doctors to replace damaged or destroyed brain cells. According to the May 7, 2013 news release on EurekAlert,

A key type of human brain cell developed in the laboratory grows seamlessly when transplanted into the brains of mice, UC [University of California] San Francisco researchers have discovered, raising hope that these cells might one day be used to treat people with Parkinson’s disease, epilepsy, and possibly even Alzheimer’s disease, as well as and complications of spinal cord injury such as chronic pain and spasticity.

“We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way,” said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF [University of California San Francisco] and co-lead author on the paper.

The May 7, 2013 University of California San Francisco news release by Jeffrey Norris, which originated the release on EurekAlert, provides more detail about the work,

The researchers generated and transplanted a type of human nerve-cell progenitor called the medial ganglionic eminence (MGE) cell, in experiments described in the May 2 edition of Cell Stem Cell. Development of these human MGE cells within the mouse brain mimics what occurs in human development, they said.

…

To generate MGE cells in the lab, the researchers reliably directed the differentiation of human pluripotent stem cells — either human embryonic stem cells or induced pluripotent stem cells derived from human skin. These two kinds of stem cells have virtually unlimited potential to become any human cell type. When transplanted into a strain of mice that does not reject human tissue, the human MGE-like cells survived within the rodent forebrain, integrated into the brain by forming connections with rodent nerve cells, and matured into specialized subtypes of interneurons

The researchers are investigating applications other than brain cell replacement or repair (from the UCSF news release),

Previously, UCSF researchers led by Allan Basbaum, PhD, chair of anatomy at UCSF, have used mouse MGE cell transplantation into the mouse spinal cord to reduce neuropathic pain, a surprising application outside the brain. Kriegstein, Nicholas and colleagues now are exploring the use of human MGE cells in mouse models of neuropathic pain and spasticity, Parkinson’s disease and epilepsy.

“The hope is that we can deliver these cells to various places within the nervous system that have been overactive and that they will functionally integrate and provide regulated inhibition,” Nicholas said.

The researchers also plan to develop MGE cells from induced pluripotent stem cells derived from skin cells of individuals with autism, epilepsy, schizophrenia and Alzheimer’s disease, in order to investigate how the development and function of interneurons might become abnormal — creating a lab-dish model of disease.

There is at least one hurdle to be overcome (from the UCSF news release),

One mystery and challenge to both the clinical and pre-clinical study of human MGE cells is that they develop at a slower, human pace, reflecting an “intrinsic clock”. In fast-developing mice, the human MGE-like cells still took seven to nine months to form interneuron subtypes that normally are present near birth.

“If we could accelerate the clock in human cells, then that would be very encouraging for various applications,” Kriegstein said.

Here’s a link to and a citation for the researchers’ paper,

Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development by Cory R. Nicholas, Jiadong Chen, Yunshuo Tang, Derek G. Southwell, Nadine Chalmers, Daniel Vogt, Christine M. Arnold, Ying-Jiun J. Chen, Edouard G. Stanley, Andrew G. Elefanty, Yoshiki Sasai, Arturo Alvarez-Buylla, John L.R. Rubenstein, Arnold R. Kriegstein. Cell Stem Cell, Volume 12, Issue 5, 573-586, 2 May 2013

Copyright © 2013 Elsevier Inc. All rights reserved.
10.1016/j.stem.2013.04.005

This research put in me in mind of my Mar. 15, 2013 posting titled, Growing a tooth—as an adult, when I featured research at King’s College London where scientists had successfully used mouse stem cells to  grow teeth in adult mice. The researchers hope to one day be able to do the same in humans.