I'm Lucy Donaldson, Professor of Sensory Physiology. Ask me anything about arthritis-related pain, pain research in general, and why we use animals in research.

This AMA is being held because it is World Arthritis Day today (12th October 2018) (https://www.eular.org/world_arthritis_day.cfm). I have been researching arthritis-related pain since I was a PhD student, and now I lead a lab of researchers working on various aspects, including some work on new analgesic drug development. Our research focuses on improving our understanding of why arthritis is painful, why some people might get chronic pain and why others don’t, and how the function of the nervous system contributes to this. We use research techniques ranging from study of molecules involved in nervous system signalling, through cells cultured in dishes, to whole animal models which includes mild models of arthritis in rats and mice. Ask me anything about the research methods we use, including why it is sometimes necessary to use animals in scientific research. This AMA has been arranged in conjunction with Understanding Animal Research (http://www.understandinganimalresearch.org.uk/) and Versus Arthritis (https://www.versusarthritis.org/), UK charities that support biomedical research communities in the UK. UAR works to inform researchers and the general public about the good research practice, the humane use of animals and the consideration of animal welfare in research, the role this research plays in the scientific process (http://www.understandinganimalresearch.org.uk/about-us/uar-position-on-the-use-of-animals-in-research/), the 3Rs (https://www.nc3rs.org.uk/the-3rs) , and the principles of openness (http://concordatopenness.org.uk/) around the use of animals in biomedical research.

Proof https://twitter.com/Harassedacadem/status/1050749342003449857

Comments: 564 • Responses: 12  • Date: 

hoverface136 karma

Is anything like a prednisone without the horrible side effects in the works?

harassedacademic120 karma

There's a real push to develop good treatments for arthritis, and other painful conditions at the moment. This is not just because there are lots of people round the world who have chronic pain, but also because some of the pain killers that are used have the problem that people can become dependent on them. The opioids are presenting such a problem, especially in the United States, where there are lots of things being done to enable the development of new pain killers. Of course, considering prednisone, which is used to try and control the disease and not just as a pain killer there are additional challenges in trying to get better replacements.

The ultimate aim would be to try and tackle the arthritis disease process, as well as the pain. As I said in an earlier reply there isn't a direct relationship between the joint damage and the pain people experience, so joint damage can be present without pain, and vice versa. Trying to stop the disease process depends on the type of arthritis - osteoarthritis and rheumatoid arthritis are very different, but there are new treatments in development that are aiming to stop disease and/or deal with the pain. There are lots of fairly new biotech companies doing really interesting work in this area, developing better pain killers, and early work in tissue engineering and regeneration is working on repairing the damage. For rheumatoid arthritis, there are biologic drugs that, that in many people can control the disease and hence the joint damage. Unfortunately drug development is a length process, but there are new drugs coming through clinical trial at the moment, such as the anti-nerve growth factor treatments for osteoarthritis pain, that look very promising.

bakerybuff57 karma

What are the effects of diet with Rheumatoid Arthritis? I’ve heard many different diet choices help control inflammation but they tend to be conflicting or extremely limited.

harassedacademic70 karma

Interesting question, and a topical area considering the wide discussions on diet and health. Most of the investigation and evidence in this area is indeed limited, because these interactions are very complicated. It's clear that there are some associations between diet and rheumatoid arthritis. Some diets such as the Mediterranean diet rich in wholegrains, legumes, fruit, vegetables, good olive oil and low red meat intake MAY be associated with a lower risk of rheumatoid arthritis. We must remember that an association is not the same as a cause - so we couldn't say, for example that a particular diet causes rheumatoid arthritis or makes it worse. As far as the influence of diet on rheumatoid arthritis itself goes, there is some evidence that, for example n-3 polyunsaturated fats (PUFA) supplementation might reduce inflammation and help rheumatoid arthritis in that respect, but many of these trials are limited because of the complex nature of the interactions between the disease and diet.

CalmEnthusiasm46 karma

Are there any studies or validity to the lack of certain gut bacteria not being present or an over abundance of a certain gut bacteria, directly or indirectly causing certain arthritic conditions?

(Seems like gut bacteria are being blamed for everything now days).

harassedacademic51 karma

There is growing evidence for a contribution for gut bacteria influencing chronic inflammatory and autoimmune diseases, such as arthritis, and particularly rheumatoid arthritis, yes. Again, this sort of evidence gives us information on associations between the diseases and the gut bacteria - most of these diseases have many different factors that influence them, but the evidence is certainly growing that gut bacteria are something that we should not ignore!

O-hmmm30 karma

I have been hearing a lot of buzz about stem cell treatments. They say new cartilage and tissue can be reproduced.

Is this something to look into now or is it too soon?

harassedacademic24 karma

There's certainly a lot of work going on in this area at the moment, in regenerative medicine, and so I don;t think it's too soon to be thinking about it as a possible treatment. There are some very early stage clinical trials on this, still at the point of working out whether it's safe, whether it will be effective as a treatment, and whether it is feasible in terms of getting real repair to the joint. Many people are very hopeful about this approach but it's early days. Of course, we don't yet have any ways to stop or modify the disease and joint damage in osteoarthritis, and no way yet to repair the damage done, so this is a really important research area to pursue.

FG39V9-126 karma

In your professional opinion do you think arthritis can go undetected even after ultrasounds, X-rays and blood tests? I have had severe joint pain from the age of 14 and have been having tests all year and apparently there's no sign of arthritis or carpal tunnel.

Edit: rumatoid arthritis runs on mums side and my father had arthritis from his early 20s but not sure what sort

harassedacademic32 karma

Joint pain can certainly happen without any evidence of any changes in the joints themselves, and it's very difficult for people when this happens, as I am sure it is for you. If there is no active joint disease, and inflammation, many investigations will detect very little, and X-rays can often show no change in joints even when pain is present. Blood tests are looking for specific things, and again pain can be present without any of those changes being able to be detected in the blood.

We always associate pain with something going wrong - that's what we believe drove the evolution of the nervous system ability to signal damage with this sort of sensation, so we would know that we might or had damaged ourselves, and we'd be able to protect ourselves from further injury. When we have pain and can find no obvious cause it is really difficult, because the pain is a real experience but there is no concrete event or injury that it can be linked to. Sometimes people in pain are not believed, just because of this lack of evidence of any obvious 'cause', and that is a very difficult thing to deal with.

All I can suggest is that you keep talking to your doctor, and maybe discuss whether you should be referred to a rheumatologist?

ChesterCharity19 karma

What are your feelings about the use of medical marijuana to treat arthritis pain?

I ask because my father was diagnosed with psoriatic arthritis about 15 years ago, and his doctor originally prescribed him with opioids to treat the pain. He had some bad side effects to the medication such as falling asleep at the wheel and various instances of sleep-walking, and for a time had to use a wheelchair because the medication wasn't helping the pain enough. Eventually he got his medical marijuana license and begun replacing the opioids with it until he stopped taking them altogether. He now takes Humira regularly as well as using medical marijuana for the pain and is in the best condition he's been in since years before his diagnosis.

Do you think medical marijuana can be a more healthy option for treating pain, or is it more likely that the Humira is just suppressing it enough to where the pain doesn't bother him as much?

harassedacademic23 karma

The Humira will be helping control the disease - it blocks a molecule called TNF-alpha that is very important in the inflammation and disease processes in many autoimmune diseases such as psoriatic arthritis, and so it should be suppressing the disease process. It's not always the case that suppressing disease also controls pain, although in many people it does. From your question it sounds as though your father uses the medical marijuana to control pain only when it is bothering him, and not all the time, so it sounds to me as though this combination is controlling both his disease and pain, at need. If it works, and he is not experiencing any side effects that are interfering with his quality of life, then it seems to be a good combination for him.

SquireCD19 karma

Does "remission" mean no pain at all? I'm newly diagnosed, and I have no idea what to expect for the rest of my life.

harassedacademic23 karma

Remission is often used to refer to when the active arthritis is under control, usually in rheumatoid arthritis. This can be achieved in many people using drugs, especially the newer biologic drugs that can control the inflammation and progress of arthritis and thus the damage caused in the joints. With respect to pain, there is a disconnect between whether there is active disease and the presence of pain - one of the problems that research is trying to tackle is why some people may not have signs of active arthritis but may still have pain, or conversely that there may be evidence of joint damage and no pain. We still really don't understand the relationship between damage to the joint and pain at all. It can be that pain can come and go, and that may be related to whether you have active arthritis, or not, but I'm afraid it's not always completely predictable. For many people though, when the arthritis is under control, pain is also reduced.

harassedacademic18 karma

Thanks for your questions. I'm going offline now, but will check in again later.

ICE_MF_Mike12 karma

What options are there now or in the future to treat arthritis without taking meds that compromise the immune system and risk Serious infection?

Also any insight into how CBD or Medical Marijuana can play in this space?


harassedacademic22 karma

There are several new drugs coming through that will target pain without effects on the immune system. However with respect to rheumatoid arthritis, because this is an autoimmune disease, drugs need to be targeted against those effects in order to stop the disease process. Not all of the effective drugs that modify disease do affect the immune system, but sometimes it is necessary to use the ones the ones that do, but they have obvious problems with infection risk.

Medical marijuana can be effective for some people, like many other pain killers. It was announced yesterday that medical marijuana will be able to be prescribed in the UK from November 1st this year, so that may now be available and effective for some people.

BEANandCHEE3 karma

I’m pretty sure I have Psoriatic Arthritis, I have an appointment with a rheumatologist on Halloween so I’ll get an actual diagnosis. I’ve been losing my fingers to dactylitis slowly over the past year and now it’s moving into my knees and is very painful. Is there any over the counter stuff I should be doing in the meantime before I get my appointment?

harassedacademic10 karma

If you are going to take anything over the counter, please check with the pharmacist to make sure that you are not already taking anything that might be a problem, as drugs can interfere with each other, and that can be dangerous. Your pharmacist is the expert in this area so they are the best person to check with before you take anything OTC. I'm not a medical doctor, so can't really advise you very much in this area, other than general advice around OTC pain killers. The non-steroidal anti-inflammatory drugs like ibuprofen can help some people, but there is a real risk of stomach damage and bleeding which can be severe. Paracetamol is a good painkiller, but really only when you have taken it for at least 48 hours at the recommended dose AND ABSOLUTELY NO MORE than recommended. Paracetamol takes about 48 hours to get to a fully effective concentration in your body, and so while a single dose might not seem to have much effect, taking it regularly and according to instructions can help some people. Please, please check with your pharmacist before you take it - or anything - for any period of time though, as many OTC drugs can cause problems.

hansyhobs3 karma

How do you manage animal welfare whilst studying pain?

harassedacademic13 karma

That's a really good question. We are required by law to have permission from the Home Office to do any experiments involving animals. We have to explain how we will minimise any effects on the animals, before we do anything, in order to get the permission to do the experiments. The potential harm to the animals is weighed against the benefits of the research before we get a licence to do the research. We are also obliged to use the most refined methods we can, meaning that we use the mildest possible models of arthritis - for example limited to only one joint, and as mild as possible. Finally, or should I say first, before we can do any experiments on animals we have to show that there is no other method that we could use that doesn't use animals. In some cases we can, and do use painkillers, sometime working out how painkiller work is part of the experiments. Above all animal welfare is enshrined in the law surrounding our work, and so we have to think about the impact on the animals all the time.

hansyhobs5 karma

Thanks for answering. What makes rats and mice good animal models for studying pain? Do they develop arthritis naturally?

harassedacademic6 karma

Again a very good question. Rats and mice are used a lot in research, but they don't spontaneously develop arthritis. Some guinea pig strains do develop osteoarthritis-like changes in their joints with age starting at about 9 months of age, but they are not commonly used.

The question of whether particular animal models are good models for a specific human disease is of course always under debate - I think that most people would agree that the models we have can give us some information on certain aspects of human disease mechanisms, but they cannot model human disease in every respect. Rats and mice are most commonly used in this research because we know a lot about their physiology, and there are reasonable models that have given us good information on both pain, pain killers and the processes of arthritis itself, that have enabled us to identify similar changes in people with chronic pain.

There is a lot of debate in the research field about animal models - pain is after all subjective experience for people, it's about how you feel, and rats and mice can't tell us about that aspect of their experience very well - but in my view I think we can learn a lot about pain from rats and mice. We have to acknowledge that, even if they do have differences when compared to people, we are successfully developing effective drugs based on what we have found from experiments with rats and mice. The new anti-nerve growth factor drugs in trial for osteoarthritis pain, and another new pain killer for neuropathic/nerve injury pain targeting the angiotensin-2 receptor are two examples of potentially very effective new pain killers that were originally developed using experiments in rodents.