Our Brain May Make It's Own Weed!!!

[G0S2]

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Nature 435, 1108-1112 (23 June 2005) | doi: 10.1038/nature03658

An endocannabinoid mechanism for stress-induced analgesia

Andrea G. Hohmann1, Richard L. Suplita1, Nathan M. Bolton1, Mark H. Neely1, Darren Fegley2, Regina Mangieri2, Jocelyn F. Krey3, J. Michael Walker3, Philip V. Holmes1, Jonathon D. Crystal1, Andrea Duranti4, Andrea Tontini4, Marco Mor5, Giorgio Tarzia4 and Daniele Piomelli2

Top of page
Abstract
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia1, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol2 (2-AG) and anandamide3. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase4, 5, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase6, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

 

[UTSouthwestern]

Nature 435, 1108-1112 (23 June 2005) | doi: 10.1038/nature03658

An endocannabinoid mechanism for stress-induced analgesia

Andrea G. Hohmann1, Richard L. Suplita1, Nathan M. Bolton1, Mark H. Neely1, Darren Fegley2, Regina Mangieri2, Jocelyn F. Krey3, J. Michael Walker3, Philip V. Holmes1, Jonathon D. Crystal1, Andrea Duranti4, Andrea Tontini4, Marco Mor5, Giorgio Tarzia4 and Daniele Piomelli2

Top of page
Abstract
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia1, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol2 (2-AG) and anandamide3. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase4, 5, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase6, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

UTHSC San Antonio. That brings back some memories. Is the Sherman Klump lookalike still the Dean of the medical students?

 

[G0S2]

UTHSC San Antonio. That brings back some memories. Is the Sherman Klump lookalike still the Dean of the medical students?

You mean this guy, Dr. Lawrence?? Yeah.

http://som.uthscsa.edu/Admin.html


I have to be nice to him since he was the one to grant my deferral.

 

[jetproppilot]

Nature 435, 1108-1112 (23 June 2005) | doi: 10.1038/nature03658

An endocannabinoid mechanism for stress-induced analgesia

Andrea G. Hohmann1, Richard L. Suplita1, Nathan M. Bolton1, Mark H. Neely1, Darren Fegley2, Regina Mangieri2, Jocelyn F. Krey3, J. Michael Walker3, Philip V. Holmes1, Jonathon D. Crystal1, Andrea Duranti4, Andrea Tontini4, Marco Mor5, Giorgio Tarzia4 and Daniele Piomelli2

Top of page
Abstract
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia1, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol2 (2-AG) and anandamide3. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase4, 5, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase6, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

 

[UTSouthwestern]

You mean this guy, Dr. Lawrence?? Yeah.

http://som.uthscsa.edu/Admin.html


I have to be nice to him since he was the one to grant my deferral.

Ahhhh yes, Leonard Lawrence. Could never quite figure out what he actually did for the program, but oh well.

Nan Clare was always the go to guy/gal for us. I see they are still having problems finding a stable IM chair.

 

[G0S2]

Ahhhh yes, Leonard Lawrence. Could never quite figure out what he actually did for the program, but oh well.

Nan Clare was always the go to guy/gal for us. I see they are still having problems finding a stable IM chair.

I had no idea that you went to UTHSCSA. Nice. My father is a professor of gas there. Do you feel like UTHSCSA does a good job in preparing students??

 

[ultraconsrvativ]

Nature 435, 1108-1112 (23 June 2005) | doi: 10.1038/nature03658

An endocannabinoid mechanism for stress-induced analgesia

Andrea G. Hohmann1, Richard L. Suplita1, Nathan M. Bolton1, Mark H. Neely1, Darren Fegley2, Regina Mangieri2, Jocelyn F. Krey3, J. Michael Walker3, Philip V. Holmes1, Jonathon D. Crystal1, Andrea Duranti4, Andrea Tontini4, Marco Mor5, Giorgio Tarzia4 and Daniele Piomelli2

Top of page
Abstract
Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia1, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB1 receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol2 (2-AG) and anandamide3. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase4, 5, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase6, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

Maybe this is why I can't remember anything when I'm stressed out.

 

[VentdependenT]

Maybe this is why I can't remember anything when I'm stressed out.

Well at least our brains don't make their own crack. Wait a minute....

 

[G0S2]

Well at least our brains don't make their own crack. Wait a minute....

Research project in the making???

 

[UTSouthwestern]

I had no idea that you went to UTHSCSA. Nice. My father is a professor of gas there. Do you feel like UTHSCSA does a good job in preparing students??

I think it does an adequate job. Not much cutting edge stuff is done there and if there is something interesting, there is usually no room or time for med students to get involved. We always seemed to be a step behind the trends and the facilities, especially the Audie Murphy VA were at times downright dungeonesque. I've heard that University Hospital has done some remodeling.

I'm not sure about the anesthesia department. When I was there it seemed to be a very stable department with a lot of published texts, but there were issues with CV numbers and the neurosurgery department that arose. Losing the chairman didn't help either. Overall, a very stable teaching staff which I think makes it a good place to train.