INFLAMMATION IS NOT THE BAD GUY IN OSTEOARTHRITIS
WHAT IS INFLAMMATION?
“Inflammation is a local defensive response to tissue injury of any kind, including trauma and infection. Its general purposes are (1) to limit the spread of pathogens and ultimately destroy them, (2) to remove the debris of damaged tissue, and (3) to initiate tissue repair.”(Saladin, 2004)
THE 4 STAGES OF INFLAMMATORY HEALING
(USING A SKIN BURN AS AN EXAMPLE:)
1. 0-10 hours after the burn is the:
The burn damages blood vessels which then leak out blood into the surrounding tissue. This bleeding may not leave the body, it is often internal bleeding. Our bodies do everything that they can stop internal bleeding, lest we bleed to death. The body responds to bleeding by sending clotting agents to the damaged area to block the leakage up.
Using the analogy of a bad skin burn:
> This is the stage where the burn starts to weep.
2: 24-48 hours after the burn is the:
ACUTE INFLAMMATION PHASE:
This is where the body gets the damaged skin ready for regeneration. After the bleeding has stopped, a temporary vasodilation response occurs. Where the walls of the capillaries become more permeable. This allows inflammatory mediators to travel out of the blood system into the interstitial space. It also aids in the removal of damaged tissue debris, blood which reduces the risk of infection. During the acute inflammatory phase dead tissue is “disinfected” and dragged away from the damaged area. Then inflammatory mediators leak out into the circulatory system, in a process of asking for help.
It is because of vasodilation that inflamed areas swell up. Vasodilation results in a rush of fluid into an area. Swelling has a number of beneficial and unwanted side-effects, called cardinal signs:
> Loss of function
It creates an artificial barrier to the range of motion, physiologically limiting the range of motion. This helps to protect unstable joint and muscles, it stops ligaments and/or muscles from being repetitively re-torn.
It is no wonder that excessively swollen joints can be painful. Mechanical swelling causes pain as different nerves get compressed:
- Ruffini-type endings= slow adapting
- Pacinian corpuscles= fast adapting
It is due to the high level of pressure within a joint that the nerves get compressed.
Swollen joints also chemically activate nerves:
- Nocioceptive Free nerve endings.
Nerves are chemically irritated by a variety of different inflammatory messengers called cytokines. Nerves are more often than not irritated within joints with ongoing swelling, as cytokines accumulate.
2: Using the analogy of a bad skin burns:
Inflammation is akin to a nurse painfully cleaning a burnt, to stop an infection from developing.
3: 48 hours - 4 weeks after the burn is the
If the above acute inflammatory phase has cleared the path for the next phase of healing. Then the damaged area sends out inflammatory messengers in the area.
These inflammatory mediators stimulate stem cells. Telling the body to send nutritious resources to the area. The growth phase occurs in damaged areas, that have the enough resources.
The growth phase is characterised by the space where the dead tissue resided being replaced with new tissue.
Pressured by the fact that tension could result in the vulnerable area getting damaged again. The body lays this new cross-linked proteins down fibrous proteins called type III collagen fibres. Type III collagen is great at resisting tensile load, but not so good at lengthening safely under load. Furthermore the collagen fibres are laid down in a rushed manner, resulting in a disorganised mesh.
Regenesis of tissue in the growth phase occurs in a 4-step process, which results in new tissue being created.
>> When it comes to growing new bone tissue
A1: Mesenchymal Stem Cells proliferate into specialised osteochondroprogenitor stem cells.
A2: These osteochondroprogenitor stem cells create fibroblasts.
A3: Fibroblasts differentiate into Osteoblasts
A4: Osteoblasts create new bone cells.
>> The regeneration of “softer” cartilage, occurs through a similar system of:
B1: Mesenchymal Stem Cells proliferate into specialised osteochondroprogenitor stem cells.
B2: These osteochondroprogenitor stem cells create fibroblasts.
B3: Fibroblasts differentiate into Chondroblasts
B4: Chondroblasts produce new cartilage tissue.
>> The process of producing new muscle cells is the most longwinded as
C1: Mesenchymal Stem Cells proliferate into specialised muscle stem cells (myosatellite cells e.t.c)
C2: Specialist muscle stem cells differentiate into fibroblasts
C3: Fibroblasts differentiate into Myoblasts
C4: Myoblasts create contractile cells (e.g: muscle)
3: Using a bad skin burn as an analogy:
This is where the burn is operated on, and a skin graft is put into place.
4: REMODELLING PHASE:
At the end of the growth phase a mesh of disorganised type III collagen fibres is left in situ. This is less than optimal as it is not as resistant to tensional forces as organised collagen fibres.
The remodelling phase is where this fibrous mesh of collagen type I, is re-organised. For all the collagen type I fibres have a life span, and naturally die, in a process called programmed cell death. Dead type I collagen fibres get broken down by enzymes called proteinases. This breaks down big chunks of proteins into proteins that can be absorbed into the body and recycled.
Dead type I collagen fibres will either be replaced by type III collagen fibres, which are more fit for purpose. Or they will not be replaced. It is force that determines whether a dead type I collagen fibre will be replaced or not. For force is the language of our cells.
The tissue gradually becomes more organised. Eventually making the tissue better able to extend without tearing when placed under tension. Through a combination of destroying dead wood and old trees are replaced with more sustainable trees.
4: Using a bad skin burn as analogy
This is where the skin graft slowly starts to become less obvious.
TAKING IT BACK TO OSTEOARTHRITIS:
What is Osteoarthritis?
“OA should not be thought of as a single disease, but rather as the clinical endpoint of numerous disorders leading to the eventual failure of one or more joints of the body.” (Sokolove, 2013)
Is inflammation to blame for Osteoarthritis?
Inflammation gets a bad name, when it comes to “diseases of old-age”. It always seems to be at the crime scenes, of metabolic diseases from cancers to cardio-vascular conditions.
Which in no way indicates that one of the healing phases somehow criminal. As our inflammatory system, is merely doing what it has been doing for millennia. It is trying to help us out. It is all too easy to forget that correlation does not imply causation.
THE REAL ISSUE IS A LIMITED ABILITY TO HEAL + REGENERATE:
It is is in the growth phase of tissue healing where most of the issues happen. When the body does not have the resources to feed cellular division/growth. Then the tissue generating stem cells produce the alternative types of cells instead. In an area of nutrient deprivation stem cells will compensate by initiating the growth of other types of tissue, such as:
> fibrotic tough collagen fibres instead, in the form of a fibrous scar. This reduce the risk of future tearing. This scar will not function well if/when stretched too far, and will not be able to contract like the tissue was before an injury.
> Adipose tissue, when the stem cells do not have access to protein or are not able to stimulate growth, then fat will be used as a substitute. This is common place. If you were to ultrasound the muscles of the thighs of someone over 80, most of the muscle mass will actually be made up of fat deposits.
Our body does what it can to self-heal, in the face of a lack of resources. Our inflammatory system is not at fault, when we get painfully stuck in the inflammatory phase of the healing cycle. Inflammation is doing its job of preparing the area new tissue to be laid down.
DON’T SCAPEGOAT THE NURSE
Blaming inflammation for osteoarthritis is akin to saying the hospital staff are at fault for a major skin burn. Just because it hurts when they clean and disinfect the burns does not make them criminals.
At first glance, it would appear that the nurse is responsible for the pain. It is easy to scape-goat, and the nurse in-front of you is the most obvious target, especially if they cause you acute pain.
If you were to dig a little bit deeper it would become clear that the nurse is NOT at fault, they are stopping things from getting worse!
The nurse is actually stopping infection, preparing the skin for the upcoming operation. Because the nurse is not able to do the skin graft. The real issue is the lack of resources available within the hospital to carry-out the next stage. Probably a lack of experienced surgeons is the underlying issue.
Our own internal nurse called inflammation does cause pain, as it makes joints swell up. But it is not at fault for a backlog caused downstream. Our internal nurse is doing its part by trying to deal with the fact that there is a backlog. As there is a delay further up the chain. So no matter what you read try your best not to blame your bodies own nurse, called inflammation. For without the next phase in the healing process can never occur.
THE IMPERFECT GROWTH PHASE
For the body to replace dead specialised cells like for like with new healthy cells is not easy. For damaged tissue to be replaced like for like, it requires that the specialised stem cell be present. Inevitably the body with fail in its ability to regenerate new like-for-like specialised cells, in what we call aging.
Wrinkles is a classic example of where the body makes do without the specialist stem cells. Our bodies make do and encourages other stem cells to step up and replace the dead skin cells, with sub-optimal skin.
As a baby we never have to worry about suffering from a lack of the right stem cell for the task at hand. Resulting in an effortless and efficient growth phase, that does not leave us stuck in the inflammatory phase. It is only as adults that a reduced capacity of healing to be specific growing, leaves us stuck in the inflammatory phase. The older we get the more likely we are to suffer from chronic inflammation, where the body cries out for growth to replace dead cells.
It is so easy to blame inflammation for a painful joint. When the inflammatory-immune system is merely trying to make the most of a bad situation.
Inflammation is rarely the root cause of pain, even when it is chronically swollen. Just because it is always at the scene of pain, does not mean it made the scene. Correlation does not mean causation. Just because the paramedic was always at a scene of an injury does not mean that they caused the injury/trauma. Inflammation is like the nurse in the hospital, whom can only do what is humanly possible.
Chronic musculo-skeletal inflammation is natural by-products of a limited capacity to heal due to:
- Repetitive damage.
- An inability to regenerate tissue.
- Kallakuri, 2012, innervation of cervical ventral facet joint capsule
- Duan, 2010, In vivo measurement of the subchondral
- Saladin, 2004, anatomy and physiology, the unity of form and function.
- McLain, 1998, Mechanoreceptor endings in human thoracic and lumbar facet joints.
- Doorn, 2012, Therapeutic applications of mesenchymal stromal cells: paracrine effects and potential improvements.
- Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!) Berenbaum, 2013
- (Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations, Sokolove, 2013)
- Cavanaugh,2006, pain generation in lumbar
- Ozsvar, 2015, Elastin-based biomaterials and mesenchymal stem cells