A new mouse painkiller in your medicine chest

This is what vets in animal laboratories need: a painkiller for mice (and other creatures) that is

— Fully effective for all strains, ages and sexes

— Completely safe with no unpleasant side effects for the mouse

— Will not interfere with the experiments – for neurobiologists, no drowsiness, disruption of Learning or other effects on brain and nerve function; for cancer biologists, no effects on immune function; for immunologists, no effects on inflammation or immunity.

— Long-acting, since you might get a monkey user to come in at night to re-dose the painkillers, but you will not get many mouse and rat users to do that

We do not have that, and so the search goes on.

Years ago, I did this wrong (I’ve written about that here): Meloxicam was a hot new dog-cat non-steroidal anti-inflammatory drug (NSAID), that might have advantages over Carprofen that we were current using, if only because the oral version is really tasty. Mouse doses of carprofen are about the same as for dogs and cats, so I started prescribing Meloxicam for mice at the same dose (around 0.2 to 0.3 mg/kg) that I’d use for dogs or cats. Two years and many under-treated mice later, the good vets in Newcastle did actual studies, and my mouse dose was about 3% of what would have actually helped those deserving animals.

And as we look for the magic long-acting safe effective non-interfering NSAID, we’re also hoping for an opioid that fits that bill.  Opioids are drugs like morphine, fentanyl, codeine and hydrocodone that work on different pathways than NSAIDs, and have less effect on the immune system. The best we’ve had to date is Sustained-Release Buprenorphine (SR-Bup). It’s not perfect and still in need of many more studies to best establish the right doses and dosing frequency, but it is now well-established in many laboratories. Scientists should resist quick changes in the pain medicines they use, as there can be subtle differences in experimental outcomes when they change things around.

SR-Bup has a big problem limiting its use, a regulatory rather than a biological problem. It’s classified as a compounded drug, not as an FDA-labeled medicine, which requires a vet’s prescription. By contrast, FDA-labeled drugs can be purchased by research facilities without relying on an individual vet’s narcotics license. For some vets, that’s a personal legal risk they don’t want to take, and I can see their point.

Enter Simbadol, a newer long-acting version of buprenorphine FDA-labeled for cats. It doesn’t require a vet’s narcotics license (though it is still an off-label use to use it for mice; not many drug companies are investing in the FDA labeling process to make mouse drugs).  NOTE: I have no financial stake in either version of buprenorphine, though I did publish a paper on SR-Bup’s use in mice.    

So, let’s all jump to Simbadol for our mice, shall we? I say, not so fast. Responsible veterinary care means evidence-based pain management. What we know so far is that it seems to work for cats, at a dose and dosing frequency determined in lab and in feline clinical trials. Will it work in mice, help them feel better and not worse (i.e., effective with minimal side effects)? How long can it last before it needs re-dosing? Will it change experimental outcomes compared to whatever painkillers the lab is currently using?

Well, we don’t know. I find two articles on-line (here and here), both very small studies, not independently replicated, and in rats, not mice. Neither found compelling evidence of effective pain management, and then, for only about an hour, not the 48 – 72 hour efficacy we are hoping to see. It’s possible that the assay they used (time until the rats move their foot from an obnoxiously hot light shone on the sole) is not the best approximation of surgical pain, so it’s possible the drug performs better in clinical use than in the lab. Possible, but we do not know. We know that very few drugs use the same amount and frequency in mice and cats, given their vastly different metabolic rates and possible differences in opioid processing.  

BOTTOM LINE #1: it would be poor practice to jump on Simbadol for treating mouse post-surgical pain at this point, without a lot more studies showing that it works, and for a long enough period of time

And BOTTOM LINE #2: we still need to know more about the other Buprenorphine formulation, especially as a sole agent without concurrent NSAID analgesics, and choice of painkillers is therefore much less important than finding non-surgical ways of conducting an experiment.

Wall Pieces

 I have never made ceramic wall art in the past. I’m very rooted in functional ware, and like living with and interacting with beautiful things that I or friends have made. And living in tiny spaces most of my life, wall space is at a premium and I worry: how much of my work deserves such an honor, or can hold up to daily viewing? In 2018-19, I made a bunch of wall-mountable stoneware and porcelain disks for my Igneous Intrusions project and gallery show (but I cheated; many of these can come down from the wall to serve as platters or trays).

Pain management details – full reporting for better science and better welfare

I’ve blogged on this before a few years back, here and here. I have published a literature review with Jamie Austin on the topic, and I’m concerned that scientists do not describe how they manage pain in their laboratory animals. In a world of on-line publishing without page limits, many journals allow thorough Methods descriptions in which scientists can hit more of the guidance in the ARRIVE guidelines for publishing animal experiments. For projects that include surgery on animals, that means describing all use (doses, frequency, duration of treatments) of anesthetics and analgesics, methods of pain evaluation, and an important poiint that none of some 800 papers I reviewed included: a clear statement that pain medicines were withheld (and why).

When scientists DO include pain management information they accomplish several good things:

They allow other scientists more information for a critical reading of the reported findings

They allow all readers the evidence that they used animals as humanely as possible

They model better animal treatment for others building on their work

When scientists do NOT include this information, they leave other scientists to think that pain medicines are optional, or worse yet, inappropriate for a particular set of experiments. Even in 2019, too many scientists in my opinion resist full use of analgesic pain medicines for their animals, and too many do that because they think others in their field will actually fault their work for using painkillers — patience: I will write about that, but it’s in some of my published writing here and here.

Hiking in Norway

Norway has a fantastic system of trails for hut-to-hut hiking. We got there in 2018. Record heat and drought made for great hiking, but not so good for the locals.

Mouse & Monkey Vet My Animal Welfare blog

In this blog, I will take you behind the scenes in animal research. My goal is to show you the animals behind news stories about medical advances. There is a harm-benefit balance in how scientists use animals, and only with detail and transparency can you evaluate for yourself the harms animals experience and the benefits scientists seek. Some of this is wonky and technical, and some is graphic (I will warn you). Some of it only tangentially touches on laboratory animals, as our impact on animal welfare reaches everywhere there are animals.