What Causes Rheumatoid Arthritis Pain?
Why ask what causes rheumatoid arthritis pain?
Today we answer a letter from a reader that raises key questions about living with rheumatoid disease (RD). Why is it so painful? Why doesn’t treatment take away pain? Why isn’t the pain dealt with? In part, the answer is found in another question: What causes rheumatoid arthritis pain?
Until recently, no one had any idea. So there have been many crazy stupid evil theories about how people with rheumatoid disease are depressed or have a newly minted maladaptive pain processing disorder.
Letter from a reader:
I just want to thank you for your help. It has been hard to deal with my RA since 2012. I am not that old only 64 but feel like 90, so what will tomorrow be like? I would like to address the pain issue, since I am not getting much help with it. I would really like to hear what you have to say about it.
Sincerely yours, Pauline
Where we stand on what causes rheumatoid arthritis pain
If someone responds very well to treatment, disease activity and pain are reduced. Unfortunately that is still a minority of people with rheumatoid disease (PRD). So, many posts on RA Warrior deal specifically with the topic of RD / RA pain: 42 with a Tag rheumatoid arthritis pain and 21 with a Tag pain tolerance / RA stoicism.
Let’s take a moment to see where we are on the topic of what causes rheumatoid arthritis pain:
1) As I wrote last year on the role of pain in RD / RA, Pain is the body’s primary indicator of a problem. Pain has always been an obvious symptom of rheumatoid disease activity.
2) Part 2 of that series discussed the popular idea of so-called remaining pain in RA, pain that is leftover after disease treatments are given, regardless of other remaining symptoms.
3) Part 3 dug deep into the data to show that remaining pain is actually a useless model since RA pain persists as long as the disease is active.
But why, Kelly? Why does RD / RA cause pain? And why isn’t there enough help for RA pain?
Science is finally bringing some answers. They are answers that vindicate PRD by exploring what really causes rheumatoid arthritis pain.I’m only 64 but feel like 90, what will tomorrow be? …address pain since I’m not getting much help Click To Tweet
A protein causes rheumatoid arthritis pain?
Experiments in molecular pain research at the Karolinska Institute in Sweden have shown that autoantibodies against citrullinated proteins (ACPA) can produce pain without any signs of inflammation or swelling.1
(Don’t let the long words trouble you: ACPA are what is tested in an anti-CCP test, the most specific test for RD.)
According to the investigators, some types of ACPA could cause long-lasting pain even in the absence of classic inflammation symptoms. Other laboratory research by the same Institute also demonstrated ACPA’s role in joint destruction.2
Read this slowly a couple of times for it to sink in: Laboratory research is separating pain from inflammation,1 destruction from inflammation,2 and “clinical disease activity” (swelling) from structural damage.3 This represents a change in the template for this disease.
For years I have advocated such change based on facts that patients report. Why do a majority of PRD report times of “invisible illness” when they suffer pain, stiffness, weakness, or disability without obvious external swelling? The reason is that many assumptions about RD are wrong. They were not based in either research with patients or the laboratory.
For example, what causes stiffness? They claim it’s just swelling. But what about stiffness that occurs without swelling?
What if we find biological causes for rheumatoid arthritis pain?
What if biochemistry and biophysics are able to demonstrate what causes rheumatoid arthritis pain and it has nothing to do with laziness or weakness or secondary gains?
What if PRD did not have to deal with assumptions that their illness was due to character flaws? Then we could find the true causes of disease activity, including pain. And we would do whatever is necessary to humanely treat Pauline’s (and our) pain in the meantime.
If ACPA causes rheumatoid arthritis pain, then we’re not crazy. The molecular pain researchers didn’t put it like that. But I’ve read that paper at least ten times in the past year and that’s what I heard.
If molecular pain research shows ACPA /anti-CCP causes RD /RA pain, then we’re not crazy. #rheum Click To TweetRead this excerpt from their conclusion and let me know what you think.
WHAT DO YOU THINK ABOUT THE NEW RESEARCH SHOWING ANTIBODIES ACT DIRECTLY TO CAUSE PAIN?
WHAT IS YOUR EXPERIENCE WITH PAIN AND NO OBVIOUS SWELLING IN YOURSELF, LOVED ONES, OR PATIENTS?
HAVE YOU HAD YOUR ANTI-CCP / ACPA TESTED?
In honor of new proof we are not crazy, I created a new design in our RA Warrior store. Click here to see a few items with the new I am not my Rheumatoid Disease design.
Recommended reading
- Rheumatoid Arthritis Swelling, Take Two
- What Does Rheumatoid Arthritis (RA) Look Like?
- Remaining Pain in Rheumatoid Arthritis
- Rheumatoid Arthritis Statistics
FOOTNOTES
1 Wigerblad G, et al. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism. Ann Rheum Dis. 27 Nov 2016;[cited 2017 Mar 24]75:730–738. DOI: 10.1136/annrheumdis-2015-208094
2 Krishnamurthy A, Vijay J, Hensvold H, et al. Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone destruction. Ann Rheum Dis 2016;[cited 2017 Mar 26]75:721–9. DOI 10.1136/annrheumdis2015208093
3 Villeneuve E, Haraoui B. Uncoupling of disease activity and structural damage. Does it matter clinically? Ann Rheum Dis 2013;[cited 2017 Mar 26]72:12. DOI:10.1136/annrheumdis2012202650
Am i understanding this correctly to mean that high anti-CCP levels point to pain even in the absence of clinical symptoms of inflammation and swelling? But most doctors use anti-CCP as a measure of disease activity. So what is new about this? And what about “remaining pain” when blood markers like anti-CCP do not show disease activity?
Anna,
Neither in my years of research and talking with investigators nor as an RD patient since 2006 have I ever heard of anyone using an anti-CCP test as a measure of disease activity. It is the most specific test done for RA/ RD, so it is often used (should be always used) in diagnosis.
Two reasons it has not been used as a disease activity measure:
1) No one knew it “did” anything. I’ve heard rheumatologists say “It doesn’t do anything.”
2) It doesn’t change with treatment. CRP and ESR and even Rheumatoid factor can go down with treatments (DMARDs or steroids), but anti-CCP does not.
I’d refer you to a page on blood tests here: https://www.rawarrior.com/blood-tests-for-rheumatoid-arthritis-what-is-their-role/
Or to the TAG for blood tests here: https://www.rawarrior.com/tag/blood-test-for-ra-rheumatoid-disease/
In answer to your second question about having pain without a positive anti-CCP lab, the answer is that there are multiple ACPAs (and multiple RF’s), but we don’t have tests for all of them for the consumer / patient at this point. That’s why the word “antibodies” is plural.
I had a +CCP of 65 (strong +). I had some pain in my hands and feet, nothing major. (I type all day at work) In fact, I came to be tested w/ANA panel because I passively mentioned it to my PCP on unrelated visit. That panel started a year’s worth of hell for me. The only test that came back + was the anti-ccp. RF, CRP, Sed, ANA all 0 or very close to it. I never had any fatigue, swelling or stiffness. The pains in my hands were and continue to be in the first/top joint closest to fingernail. The pain is minimal and occurs on my right ring finger mostly. My foot pain was sometimes in my ankles when I would go to bed at night. This dull pain has been present since I ruptured a disc in my back over 12 years ago. I freaked out over the CCP…badly! So much so that I had to go on an anti-d because I have OCD w/worry. Eventually, I went to a rheumy who diagnosed me w/RA simply due to the + CCP. She xray’d my hands, which came back as normal. Also had MRI of left hand/wrist due to sep injury…but they also looked for damage-nothing remarkable. During my exam w/her, she looked at my hands, listened to my chest and, I kid you not, squeezed one of my feet through my UGG boots and asked me if it was painful-it was not. That’s it. She prescribed Plaq. I read and read about RA and learned that my exam was quite inadequate. I read about the criteria needed to be DX’d. I read A LOT about anti-ccp and it sure seemed to me that I had RA since this test was so specific to the disease. My gut questioned the Dec 2018 diagnosis as I continued to read so I went to Chicago to get a second opinion, paying out of pocket because it was worth it to me to see someone who had more experience. I brought all of my labs-and I had a lot of them by then because I’m OCD. The appt was in Feb of 2019, at which time I had two more anti-ccp’s done-both had fallen by a 10-20 points in that time. This rheumy spent about 45 minutes w/me and gave me an exam that was absolutely far more intense than the first. I will never forget the words he said to me after our discussion and exam, “There is not a snowball’s chance in Hell you have RA right now”. He said if it were him, he wouldn’t not take the Plaquenil. I was too scared to stop it because of the mindset I’d read about-hit it hard at first-but I also know it’s a dangerous drug. I discussed this second visit w/the first rheumy and she stood by her decision to treat because of my symptoms. Honestly, she mentioned swelling-but I never had any and I told her that. Strike 2 for her. In March of 2019, I got my tonsils out solely due to tonsil stones. I quit the Plaquenil 2 weeks prior to surgery and have never taken it again. I came upon articles/studies of the link between tonsil bacteria and RA. Even though I was rarely sick and my tonsils were small, my biopsy indicated gross chronic infection-right side more than left. I needed a tie-breaker to ease my mind of this do I or don’t I have RA so in August of 2019, I went to see a highly recommended Rheumy in Aurora, IL. To make a long story short, he agreed w/Rheumy in Chicago, but said I should be watched due to the +CCP…which was now 30 (from 65). Fast forward to a follow up visit I had with him last month and my CCP is now 21(weak positive)! One away from normal. I thankfully continue to be symptom free for RA…in fact…dare I say that since my tonsillectomy I have more energy and less pain in my hands. My eyes are also brighter. So….maybe I will have RA someday…maybe I won’t. I wholeheartedly believe that the chronic low-grade infection had much to do w/the +Anti-CCP result. I wish the medical community would pay more attention to the link between the two…they seemed to many moons ago, but not now. No one should ever be diagnosed w/RA solely due to an elevated CCP. I cringe at how many Rheumy’s do this…as did mine.
Thank you for this article. Over the years, my RA/RD doc has insinuated that I’m either depressed, a hypochondriac or a malingerer. After living with knee issues for over 30 years, I finally got my knee replaced. The Orthopod doc told me I must have a high level of pain tolerance as I should have replaced the knee over 10 years ago. He simply didn’t know how I was walking without assistance on the old knee. To find there is research to support the pain issue independent of other issues makes me feel better about my mind. Of course this is the same doc that thought we should experiment by taking me off meds to “see how I do”. Bear in mind the hypocrite oath is to do no harm. After two weeks I couldn’t get out of bed. My formerly negative RA factor turned positive and my crp went crazy.
Kelly, this is such an important post, and I’ve shared it with friends who are as grateful as I am for this. In the seven years since my onset, I have had severe pain despite being on methotrexate and plaquinel. In fact, I do think that while the DMARDS affect the flu-ish feeling and exhaustion somewhat, I don’t feel like they have ever directly affected my pain levels. When one doctor referred to my pain as “remaining” or “residual” I looked at him with my jaw hanging open. These are not tiny scraps of pain by any means. I think there’s a huge misconception among doctors about how painful this disease is even with treatment. My level of pain has made me doubt my sanity, even though before my onset I was known as having a very high pain tolerance (as in not going to the ER with a broken 5th metatarsal because it felt like a sprain). I know what I experience is real, and yet it is very hard to communicate. Thank you for parsing through the science and the research and sharing it with the people who need to know!
My RA pain is constant ranging from a 4 to 8 on the 1-10 scale. Rarely any visible swelling or inflammation. Have had periods of 10 and times when I can’t grip or lift – all day stiffness – achy muscles – flu like fatigue but nothing you can see!!
Pain never goes away and never dips below a 4. Have been on MARch, Enbrel, Humira, Orencia. Waiting for Actemra.
Sorry MTX.
I am RF positive and ANA positive but never have high inflammation markers even when pain is 10.
Joints are 10 during the night – wake me up.
that can change over time Catherine. Mine used to be low also but they are sky high now. different immune signals cause different markers to rise so it changes as the disease progresses… but I was still telling the truth when my crp & esr were normal…. as are you.
Interesting. I was off the charts for ccp testing. I had little to no “hot red swelling” as some describe. I’ve had times where there has been the most unbelievable pain with little to no swelling. Other times there has been lots swelling (fluid??) but again, never the “hot red” type so often stated as a symptom. I was always perplexed that they are/were unable to somehow quantify/measure/figure out what was going on in a joint that had so much pain that I was unable to move it. I wanted a scientific REASON!! One beyond “inflammation” as a reason, because pain didn’t always correspond to that… I’m glad to know they are getting a more molecular level on these measurements. I had been well controlled on Enbrel and planquenil, but lest I forget that I have RD, I began to lengthen the injections to every 2 weeks and dropped the planqenil last year and am now paying for it.
the disease is acting directly to cause pain. I don’t know why most cannot accept that & seem to prefer to assume we are exaggerating, except for those with mild disease.
From the paper: “We found ACPA immunoreactive cells in the bone
marrow located in close proximity to CGRP+ sensory nerves,
which provides an intriguing histological link that supports the
presence of an interaction between osteoclasts and pain fibres.”
Wow. Interesting. I was an elite endurance athlete and for years I was brushed off from doctors when the pain in my feet just couldn’t be explained. Doctors suggestion? Stop training. No one gave me a blood test even when it spread to my shoulders and thumbs.
I was even pursuaded to have foot surgery in hopes that the pain in the balls of my feet would subside.
Fast forward 10 months post op and my middle finger became involved. Only blood test given was CRP which was normal. Doc sent me to a hand surgeon who said I should lay off sports.
I finally demanded an MRI on my hands and low and behold it revealed erosions indicative only to RA. Still no blood test only suggestion to begin MTX.
I sought out another Rheumatologist who gave me a full blood test and anti CCP was >200. I never had redness and very little swelling and both CRP and ESR are always normal.
Each subsequent doctor appointment I have no visable swelling and although pain persists in my ankles doc says I am doing well and not to worry. Now I am worried as I’m afraid that the disease will just continue to progress.
Thanks for the article. It gives me pause and although I know we need to find more biomarkers I’m left wondering why so many people on different forums don’t speak often about anti CCP. Even if it is only a disgnostic tool it seems to tell a whole lot more.
I’m even more perplexed why some people with high anti CCP don’t get bone erosions and some people do. So much more to learn!
Thank you Kelly.
All my blood work cm back normal except the anti-CCP. Very little swelling, warmth, etc. But at time it feels like my thumb has been slammed between 2 doors. Only the fingers on one hand are affected as of now, but both my wrists unable to bend or extend. Been told by rheumatologist I must have high pain threshold. Six years since suspected but just recently diagnosed. Symptoms began following a shoulder arthroscopy I wish I’d never had done.
Thanks Kelly. You just brought a tear to my eye. I received notification today that my insurance is denying Actemra. I am so devastated I have been holding out for Actemra. They want me to try another DMARD. Today was a rubbish, painful day too – dragging myself around.
So I’m perplexed with my pain,swelling and stiffness because I am seronegative and my anti-ccp are all notmal,but I still have significant pain any erosions on x-rays. Have you done any research or can you point me to any articles that explain why this phenomenon exists? Sometimes I question whether not it’s all in my head !!!
Hey Heidi. If you’ll notice in my article, the word “antibodies” is plural. There is more than one RF antibody and more than one type of ccp antibody. However we only test for one type of each. Over time, there is a tendency for people who are “seronegative” to become positive.
Hopefully there will be more tests in the future.
You can always use the searchbox on this site to find info you need. It’s at the bottom of the right sidebar now. I searched & found this>>
https://www.rawarrior.com/seronegative-rheumatoid-arthritis/
Originally my markers were through the roof, but with treatment came down to normal. I still had stiffness and pain but tolerable.
However, given I am currently living the exciting life of a full flare up that is resulting in horrific bursitis and tendinitis around my joints …but with apparently absolutely normal inflammation levels and CCTP (yeh sure, I shouldn’t need steriods to straighten one leg and walk) then all I have to say about an evidence based approach is thank fuck. If we pardon the French.
RD doc believes me I think – given this only resulted after he tried to reduce my medication (fair – I was doing well). I also look like a pile of crap even if all the scans are coming just dandy.
Blah.
I’ve posted here for years… I had severe, unrelenting pain as one of my major symptoms, with often very little visible swelling, and erratic blood levels for inflammation, etc. (I was dx at age 10, I’m 45 now). Last year I started on a new biologic , (Cosentyx, I know someone will ask) and after 1 year of very very slow improvement, I’d say I’m in remission. After 13 straight years of NOTHING working. I’m only sharing this because I want to emphasize that the severe pain is NOT in your head, because of depression, a character flaw, low pain threshold, etc. The new meds very slowly improved my joints, my blood markers, but most importantly my pain. I went from being barely able to cope with the pain on morphine, to being able to take an occasional Tylenol. I was starting to think it was just me, but no, the pain is completely a result of the disease. It’s absolutely NUTS that RD pain is treated any other way than being caused by RD. I know my symptoms will be back at some point (no treatment has ever worked for me longer than 3 years) but I’m glad after 13 years to have proof that the pain is not my fault in any way, yours isn’t either.
Anne!!! (And all) I totally feel you!!! All of my tendons are shredded. I have “severe” tendonitis AND tendinosis and Bursitis in my shoulders, elbows, hips and a bulging disc in my back that came front no where! I am overweight but not obese and have been this size-even bigger-for 8+ years. My CRP & SED rates are always within normal ranges but my Anti CCP WAS over 200. THIS ARTICLE AND YOUR POST WAS SO VALIDATING for me!!!! As usual, KELLY saves the day with more information and understanding!
Catherine – if you haven’t already, try an appeal to your insurance. If they still won’t allow the Actemra, try the drug company. It is amazing how the drug companies will reduce price for those on limited incomes – and even those NOT on limited incomes. I’ll admit we haven’t found the formula for applying that will help us. But I keep hoping!
Elizabeth
Thank you for this article. Went to my support meeting today and Windy was telling us about this article. I came home determined to ‘find’ it among all your most valuable info. This helps me so much in understanding the pain I have. I don’t have a lot of swelling and the red/hot joints but I almost always have varying degrees of pain. Every single time my anti-CCP has been tested and as recent as 3 weeks ago, it is always greater than 250+. Of course 250 is as high as it goes. My Vectra DA score 3 weeks ago was 72. A difficult disease and difficult to understand. But very thankful for all your knowledge and research that you share with us. God bless you.
Thanks for this article. I was diagnosed with RA in February and have had trouble finding the right medication for me. It is all very scary so Thursday after a reaction to Methotrexate I stopped all of my meds and will see my rheumatologist Monday. I woke up this morning in immense pain but like many others I have no redness or swelling but I am ccp positive and my RF is high so this explains some of how this works for me but I’m still very confused and until the past few days I was in denial and wanted to try to not take meds and control with diet and exercise which I don’t feel like doing .. lol
Really interesting as my worst pain has not been accompanied by any visible swelling, in hip and fingers. Yet it seems to be seen as a marker by rheumatology i.e. no swelling so you’re doing well. I am strongly positive anti ccp. Same with morning stiffness, no, all day for me, bit like morning sickness ? i feel like I’m not coming up to some pre-conceived standards of the disease, when hey, its me who’s got it, i should know!
I know how I got RA. From the time I was born. I was tied up torture. My mother tried to drawn me. I was been with my dads police stick. I was chocked. Raped burned. Getting drs to understand this is so hard
I have inflammation but it’s not so much seen as docs can feel it in my joints. My struggle is because of blood work not showing anything other than being ANA positive my Rheumie doesn’t believe I have RA even though she’s diagnosed me with sero negative RA for ins purposes in order to be treated with biologics. It leaves me very confused with what I have or don’t have.
She calls it mixed connective tissue disease not yet determined.
Ugh…so frustrating.