JUNIORPROF

In a recent post on DrugMonkey, the DM suggested that I write a post on clinical trials for cannabinoids as analgesics. Due to some obligations I am quite sure that I am unable to talk about certain aspects of these trials; however, I can talk about about their rationale and why the public should know that cannabinoid analgesics need not have any association with cannabis smoking.

Let’s start this off with a little background on why cannabinoids are analgesic. Human’s have known that cannabis smoking can be analgesic for thousands of years but it is only recently that we learned why. Soon after the first cannabinoid receptor, CB1, was cloned, Andrea Hohmann and Miles Herkenham at NIH began a series of elegant studies examining the expression of cannabinoid receptors in the central nervous system (CNS) and how this expression pattern was relevant to pain. They found that CB1 receptors were expressed in the outer lamina of the spinal cord, suggesting that CB1 receptors might be involved in pain control (since this is where pain-sensing neurons first terminate in the CNS). Subsequently, it was shown that spinal injection of cannabinoids induced analgesia and that knockdown of CB1 receptor by antisense led to increased pain (hyperalgesia). These studies were done largely by Ken Hargreaves’ group. All of these findings suggested that an endogenous spinal cannabinoid system was involved in pain control. These were really the first studies to suggest a mechanism of action (MOA) for cannabinoid analgesia in the CNS.

Around the same time, a group led by the late (and far too soon I might add) J Michael Walker, demonstrated that cannabinoids could induce analgesia via another mechanism, this one also in the CNS. CB1 receptors are expressed in a particular area of the periaqueductal grey (PAG). The PAG is a major pain control center and is often considered to be the location of the brain where endogenous opioids mediate analgesia (think runner’s high). Walker’s work showed that PAG cannabinoid receptor containing neurons exerted control over neurons in the rostroventralmedial medulla (RVM). This is important because the RVM sends projections down to the spinal cord and these neurons are responsible for controlling synaptic output at the level of the outer lamina of the spinal cord. Essentially what happens is that cannabinoids activate CB1 receptors in the PAG. These neurons then modulate the output of the RVM such that the RVM exerts descending inhibition on the outer lamina of the spinal cord. All of this leads to analgesia. Hence, in the CNS, there are two major loci of cannabinoid action to cause analgesia, the outer lamina of the dorsal horn of the spinal cord and the PAG. Read more »

The new faculty development day seminars yesterday were largely centered around getting us new faculty to know our new colleagues, helping us navigate the administration of the Uni and telling us about programs that the various Deans are particularly proud of. One thing caught my eye right off the bat. The new faculty around here are much more diverse than I would have ever expected. This makes me happy. It also makes me proud of my choice in workplaces. More than half of the new faculty that showed up were female. There were also many Hispanics and African-Americans. All of this is a GoodThing; however, I feel strongly that it isn’t enough to just hire a diverse group of faculty at an institution, the institution must also make a strong commitment to career development for people that historically have been far under-represented in the biomedical sciences.

To my great pleasure, about halfway through the program another Dean got up and spent some time going over programs that the institution has implemented to make sure that this Uni will be successful in retaining this pool of talented people and in helping them develop their talents as to maximize their career potential. Let’s start with programs for female faculty members. There are several organizations on campus for female faculty that are in place to address their needs. In this cadre of programs, a few caught my eye as being especially innovative. Read more »

Today was new faculty development day at my medical school and I’d like to point out a few things I learned that might be of general interest as well as some observations on human behavior that got to me a bit. Rather than doing them all in one post I’ll break them up. So I don’t forget let’s have a little list.

This post is going to be about an observation on human behavior that all young faculty should be aware of. Next we’ll talk about 3 things that I learned today that I think are important for anyone considering a new workplace:
1) Institutional commitment to a diverse workplace.
2) Institutional commitment to research and clinical track faculty.
3) The tenure process.

So, what did I see today that got under my skin? Read more »

DM Physioprof put up a post on grad school malaise some time a week or two ago and today “B” chimed in on the problem of postdoc malaise. B’s problem is quite different than the grad school question that DM dealt with but it is an issue I have been hearing a lot lately so I thought I would cover my opinion of the issue.

B says:

It’s just coming to the end of a (way too short) 2 year appointment with the dream (tenure track job in my case) not in sight for myself and almost everyone i know who’s in a similar situation, it’s so hard to be motivated about… no, not finally my own research appointment and group, but the next postdoc! What do we do? I am so close to quitting, but anytime I say this to anyone there is a loud ‘NOOOOOOO! you can’t you’re too good at this to leave academia”. Well I’m apparently not good enough to get a job offer (everything I interviewed for went to people who were already assistant professors by the way).

Will I and my peers really feel some great relief and revival in our second postdocs after hauling ass across the country or continents and get started in yet new labs and with new people? Really? Really really? Because I see a bunch of us running on empty with no end in sight… For me, the PhD was never unattainable, doing science was never a chore. But chasing a goal that seems unattainable and spending all my time doing job applications is dreadful and makes me hate every day…

I heard many stories like this at the APS meeting last week. It seems fairly clear to me that the short window of opportunity in which I got my tenure track job is closing somewhat as institutions deal with the realities of the present funding crunch. This has a very adverse effect on postdocs that are ready to hit the job market. While it undoubtedly is not the ideal situation for people like B, it is an opportunity for people in her situation to take action for their career development, just maybe not in the way they would envision it. Read more »

Well, I’m still here at the American Pain Society (APS) Meeting in lovely Tampa Fl and once again I never got around to blogging the conference.  This time internet access was no problem, I’ve got it everywhere, but time has not allowed for any posts.  This meeting is a bit odd for a basic scientist.  There is very little new science here but there is a good deal of socializing and deal making to be done.  One of the main reasons is that this is essentially a corporate meeting.  All the Big Pharma entities are here touting there latest trials and trying to convince the physicians to write scrips for their compounds.  I’m fine with that.  Much of what they show is evidence based (rather than trying to get someone to write scrips based on taking them to some fab seats at a ball game) and there are really some nice new treatments out there for groups of patients that haven’t been helped much by other therapies.  It also appears that there is a big push to create new formulations for COX-2 selective inhibitors to make them safer.  Some of the combos are pretty interesting and I hope they find some success when their safety trials ramp up.  Another thing I’ve noticed is that if you can get your drug some bioavailability in patch form then you’ll be pumping out patches at your wonderdrug factory.  This is good news, I think.  Local actions for drugs can avoid psychotropic side effects and give you a degree of specificity that you just cannot get with P.O dosing.  If I still had my pain issues I’d be looking to try some patches (thankfully I haven’t had to worry about this so much lately).

So, PK/PD and new formulations are interesting and all, but I’m a preclinical kind of guy so what’s going on here at APS? Read more »

Q: Why aren’t white people voting for Obama in greater numbers?

A: Well, let’s see, some are racists.  Some are Republicans following the will of Rush.  Most just prefer Hillary right now.  Wait till Nov, they’ll vote for Obama then.  Why do you keep asking this question?  Do you think a primary vote means anything about who someone will vote for in November?

Q: Why do people with college educations vote for Obama in such overwhelming numbers?

A: Because they have time/motivation to actually watch the news and they understand that this country is in dire straights. They get that our international reputation is in shatters and this matters to them.  They know that Obama as president will immediately repair our image in much of the world.  They also know that there are no easy solutions to our problems and that they will take time.  Compromises need to be made and issues need to be thought out carefully with all of the evidence considered.  Anyone who proposes a gas-tax holiday obviously doesn’t get it (or will say anything to get elected).

Q: Working class whites without a college degree just won’t vote for Obama. Why?

A: First off, like I said, wait till Nov, they will.  Second, many, if not all of them did better during the Clinton administration.  They remember those years fondly and want them to come back.  Many of them got into the markets for the first time during those years and did quite well for themselves.  Then they got smacked in a way they never thought was possible.  Very little of this had anything to do with Clinton, on either end, but the correlation exists. Finally, she tells them what they want to hear and they are getting hammered right now.  Obama’s fixes will take longer but they will be sustainable.

Q: Young people are voting for Obama in record numbers.  What’s up with that Pat Buchanon?

A: He’s our generation’s JFK.  Its pretty simple.  If you’re over 33, shut up, I’m having a moment.

Q: Has the media overplayed the Rev Wright story?

A: Jesus Christ!  Are you fucking kidding me?  Shut up already, can’t you see we have some real problems on our plate here?

INTERRUPTION: Obama just said Wolfpack, that’s it, he lost my vote.

Q: Should Hillary drop out out after her drubbing in NC?

A: Of course she should but she can do whatever she wants with her campaign.  Afterall, she has virtually no chance of winning now and she is only hurting herself for her political future.  If she wants to continue to do that, it is her choice, but I think she should make a wise choice because she can and should still have a bright political future. 

That’s all for now, and Obama is speaking so time to wash down in the O-Aid.  Perhaps will get more Q and A later when the stupid question panels return to ask the same people the same tired questions for 4 more hours.  I can’t wait!

Well, aside from the lack of internet access the Cayman Pain Meeting was a big success.  I have been to this meeting several times and it never disappoints.  There were 6 days of talks and about 30 sessions with more than 100 speakers.  Each speaker gave a ten minute talk with 5 minutes for discussion.  Nearly every talk was about the latest findings (so mostly unpublished work) from the lab of the PI or the latest work of the postdoc (yes, several postdocs gave talks).  Following the morning sessions we had time to get together and talk science and I had the opportunity to meet several junior PIs at a variety of institutions who are getting some exciting research projects off the ground.  All in all, despite the funding problems we are all experiencing, these are exciting times for the pain neuroscience field.  Below are some of the major themes that emerged from the meeting….  Read more »

Well I’m at the conference and was gonna live-blog it, but, I’m having a heck of time getting wireless so this isn’t gonna work out as expected.  Turns out that everything costs a fortune in Cayman and as much as I’d like to blog from here, I’m not spending the cash they want to get wireless at the conference hotel.  I’ll try to put together a summary mid-conference and another at the end.  Until then, its an interesting conference so far with lots of new stuff being presented.  The major theme has been the role of microglia in neuropathic pain.  Several aspects of the pathway are becoming more clear including initiation and maintenance.  There have also been some good presentations on clinical candidates that are getting close to making it into humans.  More on all of this later…

Bike Monkey tagged me for the cult book theme and (sing it with me now) I always do as I’m told.  This is a bit scary because I’m afraid I may have read a good number of these books.  Then again, maybe their list isn’t hardcore enough for my tastes…

Read more »

Every two years my little subfield, the pain world, gets together on Grand Cayman island for the Spring Pain Research Conference. As you might imagine, this is just about my favorite conference (and it takes the cake for Mrs Juniorprof). Not only is the conference held in paradise, but the format of the conference is just about perfect for networking and jump-starting collaborations. The meeting itself is in the morning, 8-1, and the rest of the day is free for hanging at the beach, having some rum-based drinks and talking about cutting edge science with most of the leaders in the field.

This will be my 3rd time to go to this conference. The previous times I was either a grad student or a postdoc. This time I’m the junior PI on the scene and I’ll be presenting some work from my postdoc with a bit of data from the new lab sprinkled in here and there. Since this will be the first opportunity to talk about work that is ongoing in “my lab” I am very excited to get there and start waving the flag for the juniorprof lab. This is also a great networking opportunity. At previous meetings I frequently had the opportunity to talk about possible collaborations with other researchers but I was never in the position to be able to pull the trigger on doing such work. Its all different now and I am excited to create some opportunities for the lab through my networking activities at the conference.

Finally, I’m considering “live-blogging” the conference. The question is, dear readers, do you have any interest in reading about what’s new and exciting in the pain research field on this here blog? If so, I’ll see what I can do… if not, I’ll just tell you how nice the sand feels between my toes and post some pics of little fishies.