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Unraveling the Role of Inflammation & Pain: Two doctors share their perspectives on the inflammatory process

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Pain and Inflammation Discussed"We are beginning to understand there is a lot of overlap between the mechanisms of nociceptive and neuropathic pain and changes across the entire nervous system."Dr. Steven Stanos, DO

Inflammation is one way in which our bodies react to infection, irritation and.injury. But, what is it?

Inflammation is a highly complex process that, more often than not, helps the body heal. Remember as a kid you were taught to put ice on an injured area to reduce the swelling? That was to help reduce inflammation and the related pain and swelling.

But when inflammation doesn’t subside over time (also called a pro-inflammatory state), the related pain, redness and swelling can continue and become problematic. In fact, studies have shown that chronic inflammation can undermine one’s health, leading to a host of other health problems including arthritis, heart and lung diseases.

[The American Pain Foundation] asked two expert physicians – a rehabilitative medicine doctor and a rheumatologist who treats arthritis, lupus and other rheumatic illnesses – to help explain how inflammation and pain are linked. Each shares his perspective on the inflammatory process.

“Infection and injury trigger a complex chain of events called the inflammatory cascade.”

Q: What is inflammation?

Dr. Steven Stanos, DO (SS): [Note: Dr. Stanos is a rheumatologist and pain specialist at Northwestern University's Feinberg School of Medicine, and Medical Director of the Rehab Institute of Chicago's Center for Pain Management  See his bio at end of Q&A.]

Familiar signs of inflammation include redness, warmth, pain and swelling. Inflammation is a normal process of the body trying to heal itself. During a normal inflammatory response the nociceptors or pain receptors in the tissue are bombarded with different chemicals; these chemicals are there to help restore the healing process.

With any kind of inflammation – whether it’s from a bug bite, an infection, acute trauma or an inflamed joint, for example – there is an upregulation of the pain receptors so the tissue may be more sensitive. That’s why you’ll see redness and swelling and those are related to the chemical changes triggered by this inflammatory response.

The problem is that, over time, the process of inflammation can repeat itself even when you no longer need it. So there is a balance between inflammation that is good and useful to the body versus ongoing inflammation that can cause more signs and symptoms, and lead to pain and other dysfunction.

If inflammation isn’t useful, we need to be more aggressive in treating it. But we must remember, there is a very complex cascade of events that are triggered from inflammation. Different medicines are designed to work on different pathways of inflammation.

Q: What is inflammatory pain?

Dr. Rowland Chang, MD, MPH (RC): [Note, Dr. Chang is medical director of the Rehabilitation Institute of Chicago Arthritis Center – see his bio at end of Q&A.]

Simply stated, inflammatory pain is pain that is associated with an inflammatory condition. It is often part of a clinical picture that includes swelling, warmth, redness, and stiffness. Inflammatory musculoskeletal pain is commonly worse first thing in the morning and/or after long periods of immobility, and it generally improves after periods of physical activity.

SS: It can be related to swelling in a joint if there is increased joint fluid or proliferation of the joint lining. There are also cartilage changes with inflammation where the cartilage can break down, which is what occurs in osteoarthritis. In this case, inflammation and pain might be a result of tissue breakdown in the joint.

Q: What are the most common causes of inflammatory pain?

RC: Infections are probably the most common overall cause of inflammatory pain. Common causes of inflammatory musculoskeletal pain include many of the rheumatic diseases, such as rheumatoid arthritis and other inflammatory forms of arthritis (such as psoriatic arthritis and ankylosing spondylitis – an inflammatory arthritis of the spine), polymyalgia rheumatica (an inflammatory condition in older people that results in profound morning stiffness, shoulder and hip pain), systemic lupus erythematosus (a systemic inflammatory condition affecting the joints, skin and many internal organs), and so on.

SS: Inflammation can also affect multiple tissues whether it’s inflammation around a nerve, in the connective tissue or the joint itself. People will present differently depending on where that inflammation is. If you think of shingles pain, there is inflammation all along the nerve as it tries to heal; the inflammation is there to help the healing process, but it also causes hyper-excitability along the nerve.

With many chronic pain conditions, we believe there is a sensitization in the tissue and there can be related inflammation.
Even with something like pelvic pain, the organ tissue can get inflamed and irritated and itself can cause pain.


Among Others, Causes of Inflammation Include:
• Infection
• Trauma and injury (spraining or breaking an ankle)
• Allergic reactions
• Prolonged stress
• Certain autoimmune disorders

Q: How is inflammatory pain different from other pain types?

RC: As mentioned, inflammatory pain generally gets worse after prolonged immobility and better after physical activity. In contrast, neuropathic or nerve pain is generally constant. And mechanically driven musculoskeletal pain tends to get worse during physical activity and/or standing and better after rest, the opposite of what you would expect from inflammatory musculoskeletal pain.

SS: We classically think of inflammation as nociceptive pain – it’s considered “normal” pain or the body’s normal response to trauma or injury. We’ve always had this dichotomy between nociceptive pain versus neuropathic pain. But I think now most pain conditions are mixed. We are beginning to understand there is a lot of overlap between the mechanisms of nociceptive and neuropathic pain and changes across the entire nervous system.

For example, shingles pain in which the virus is reactivated and spreads all along the nerve will cause a very severe inflammatory response along the course of the nerve.

Another example is a disc herniation when the disc pushes on a nerve in the back and that can cause severe leg pain or sciatica. Different chemicals are released in the area and there is inflammation, which is why we would use steroids to try to decrease the pain.

Diabetic neuropathy is another, even more complex example because besides the inflammatory reactions, there are other chemical and pathophysiologic changes related to alterations in blood flow and other endocrine changes.

Q: Are certain injuries or infections associated with inflammation more likely to trigger or worsen pain?

RC: The level of inflammatory pain is generally related to how much inflammation is present and how rapidly the inflammatory response is mounted. In general, acute joint inflammation caused by infection or the monosodium urate crystals caused by gout, for example, leads to more pain than that associated with more chronic conditions such as rheumatoid arthritis.

Q: How are laboratory tests, specifically markers of inflammation found in the blood like erythrocyte sedimentation rate and C-reactive protein (CRP) levels, used to help track inflammation in people with chronic pain?

RC: Erythrocyte sedimentation rate (ESR or sed rate for short) and CRP tests can be used to follow inflammatory conditions and can be useful in helping to distinguish inflammatory versus noninflammatory conditions, but these are not perfect tests. Positive tests could occur in persons without inflammation (false-positives) and negative tests can occur in persons with inflammation (false-negatives).

Occasionally, clinicians will follow other tests that have been found to be useful in following the progression of particular diseases. For instance, some clinicians will follow the antidouble stranded DNA antibody and complement level tests (measures hyperactivity of the immune system) in patients with systemic lupus erythematosus.

SS: In patients with chronic pain, these are not as useful. But if there is a change or if we think there is an additional inflammatory problem or something else going on, we may test for that. Ideally, most patients with chronic pain don’t have elevated CRP levels because more acute inflammatory changes decrease over time. There can be other factors at play too. For example, you can have an elevated sed rate if you have the flu or an unrelated infectious process.

We will use these serum tests more intermittently with patients with chronic pain primarily if new problems arise and there is a suspicion of an inflammatory response in the body.

Q: What can someone do to help safely reduce inflammation?

RC: Treating the cause of the inflammation is the best way of treating inflammation. If it is due to an infection, using antibiotics will help combat the inflammation. If infection is not the cause, then a variety of non-steroidal anti-inflammatory drugs (for example, ibuprofen) can be tried.

Occasionally corticosteroids (prednisone is an example) are used when the inflammation is particularly severe and it leads to functionally limiting consequences (for example, when the inflammation of rheumatoid arthritis becomes so intense that a patient cannot function at an acceptable level), but this must be done with great caution because of the potential side effects of these medicines.

Chronic inflammation can also be improved with the use of omega-3 fatty acid supplementation and probably with moderate intensity physical activity (for example, fast-paced walking or swimming).

However, physical activity can worsen acute inflammatory conditions, so rest is generally advised when an infection or other acute inflammatory conditions (for example, gouty arthritis or an acute asthma attack) occur.

If you suspect acute inflammation or if chronic inflammation appears to be worsening, you should consult your health care provider.

In addition to treating the root cause of the inflammation, treatment is often focused on:
• Avoiding or modifying activities that worsen pain
• Relieving pain through pain-relieving and anti-inflammatory medications (for example, NSAIDs)
• Maintaining range of motion and muscle strength through physical therapy
• Decreasing stress on the joints by using braces, splints or canes as needed.

SS: It depends on the root cause of the inflammatory response, as Dr. Chang mentioned. If we are talking about reducing inflammation from an injury, it’s important to apply ice to the area which may help decrease some of the swelling.

You also want to keep the joint mobile with an inflammatory reaction, because if you don’t move the joint, the joint capsule and related tissue may contract and get tighter, which can lead to more pain. So applying ice, trying to remain active and maintaining range of motion of the joint are all important.

Inflammation can also be a sign there is a biomechanical problem.

Stretching and strengthening the muscles above and below the joint that is inflamed can reduce the pressure through the joint and reduce inflammation. As a rehab physician, if there are signs that there is a biomechanical deficit and you don’t address that, inflammation is going to continue. If this is the case, medications can only help so much.

Physical medicine physicians and therapists can work with patients to help restore normal function and improve structure and tissue function around the joint.

There are pharmaceutical companies that are close to getting approval for nerve growth factors – if you can modulate or affect these nerve growth factors that are also stimulated, they show it can reduce inflammation in osteoarthritis pain. This will be a huge change for patients if they come to market.

* * * *

[Two of America’s Top Pain Doctors]

Rowland Chang, MD, MPH,  is medical director of the Rehabilitation Institute of Chicago Arthritis Center and professor of preventive medicine, medicine, and physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

He is a rheumatologist with more than 28 years of clinical experience. His major clinical interest is in rehabilitative rheumatology, and he is regarded as an expert in this field. He is the immediate past chair of the rehabilitation section of the American College of Rheumatology and co-author of the rehabilitation chapter in Koopman’s and Moreland’s textbook, Arthritis and Allied Conditions, one of the major international rheumatology textbooks.

Steven Stanos, DO is assistant professor in the Department of Physical Medicine & Rehabilitation and assistant program director of the multidisciplinary pain fellowship at Northwestern University Feinberg School of Medicine, Department of Anesthesia, in Chicago.

He is also medical director of the Center for Pain Management (CPM) at the Rehabilitation Institute of Chicago. Dr. Stanos directs the center’s interdisciplinary pain program. In 2009, the CPM was awarded the American Pain Society Centers of Excellence Award for comprehensive treatment of chronic pain, the first rehabilitation hospital-based program to receive this designation.

Dr. Stanos is currently involved in studying clinical outcomes in multi and interdisciplinary pain treatment, and serves as an investigator in a number of ongoing pharmacological drug trials related to the treatment of chronic pain.


* This article was reproduced with generous permission of the American Pain Foundation.© American Pain Foundation, 2010, all rights reserved. It is excerpted from the Winter 2011 issue of the APF’s newsletter, Pain Community News (Vol 11, #1), editor Amanda Crowe, MA, MPH.

Note: This information has not been reviewed by the FDA. It is general information and is not intended to prevent, diagnose, treat or cure any illness, condition or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and reviewing it with your professional healthcare team.

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2 thoughts on “Unraveling the Role of Inflammation & Pain: Two doctors share their perspectives on the inflammatory process”

  1. IanH says:

    These are very informative articles but are also standard “macro” explanations of inflammatory pain. It would have been useful if an attempt had been made to include FMS and ME/CFS in the explanations. I know that would be a challenge but we are beginning to understand some of the immunological factors in inflammatory induced pain. If standard tests/signs of inflammation are used then one can conclude that FMS and ME/CFS do not show signs of inflammation. However if we look at the immunological level we see a consistent inflammatory response. This response is more pronounced following physical exercise.(See the work of Prof. Alan Light). The pro-inflammatory cytokines, IL-1b, IL-6, Il-17 as well as a number of neuropeptides responsible for neurological inflammation are up-regulated.

    For people with FMS and ME/CFS, it is this level of inflammation which produces some of the symptoms. Such as post exertional fatigue, morning stiffness, persistent tendon aching.

    The need to keep moving is legendary in FMS. Why is this? What does this constant movement do?

    The idea of an over sensitive brain explains nothing. The CNS is affected by the immunological “inflammatory cascade. To alleviate pain appropriately in FMS we need to alter this. Taking analgesics or antidepressants are fine as far as it goes but we must get past them.

    1. IanH says:

      Post operative neuropathy is also an interesting phenomenon and can shed light on FMS.
      For example, a “normal” patient has an orthopaedic operation on a knee but after coming out of anaesthetic he complains of a lot of shoulder pain and believes he was mis-handled during the op. Scans of the shoulder show nothing remarkable. On further questioning he reveals that he had an injury in that shoulder over 1 year ago while playing football but it hadn’t bothered him since. The pain settles down after about three weeks. We need to understand the immunology involved to explain this. Mild injury does not heal 100% and later inflammatory activation will send cytokines into that area (shoulder) as well as the activated area (knee). The immune response switches off but in someone with FMS we would expect that response to continue for far longer than in the above patient. That is seen in the following example:

      A 43 year old man with FMS has a car accident and suffers a mildly crushed thoracic vertebra. Surgery repairs the problem but after the operation his lower back pain increases and his wrists become very stiff and more painful. After two months of increased pain, despite being on amitryptiline his l. back is scanned and his wrists tested for carpel tunnel compression. The lower back scan is unremarkable but the neurological tests show some slight possible carpal tunnel problem but not indicating surgery. His extra pain and stiffness is explained as part of FMS. I had no doubt that the extra pain and stiffness were caused by an immune system attack on old injury of the l. back (which he subsequently reported) and of the “mild” carpal tunnel compression. These sorts of events are common with FMS. It is also why some people with FMS report worsening pain after a bout of food induced digestive disturbance (gastritis, diarrhea and nausea).

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