Alarmins, cause of persistent knee pain

Alarmins: The Hidden Reason Your Knee Pain Keeps Flaring Up

Why your knee “screams” even when scans look normal — and how to calm the biology behind it

In This Article, You Will Learn:

🔷 Summary: What You Will Learn

  • What alarmins are
  • Why they trigger sudden knee pain flare-ups
  • How diabetes, insulin resistance, and metabolic stress magnify inflammation
  • Why your MRI can look “normal” while the pain is severe
  • How we treat alarmin-driven knee flares at Madras Joint Rejuvenation Centre (MJRC)

 

See this video –


🔷 What Are Alarmins?

When your knee joint cells experience stress — from injury, overload, poor metabolism, or inflammation — they release small emergency molecules called alarmins.

Think of alarmins as your joint’s chemical SOS signal.

They alert the immune system:
“Something is wrong — send help immediately!”

Initially, this is protective. But when alarmins stay elevated for too long, the joint becomes stuck in flare-up mode.


🔷 The “Alarmin Cascade”: Why Inflammation Doesn’t Switch Off

The process is simple:

  1. Joint tissues become stressed (overload, metabolic stress, cartilage wear)
  2. Alarmins are released (distress signal)
  3. Immune cells rush in (the joint becomes “hot”)
  4. Inflammation rises suddenly (pain, swelling, stiffness)
  5. Resolution fails (flare lasts longer than expected)

This “failure to switch off” is extremely common in diabetes, obesity, insulin resistance, and metabolic syndrome because their inflammatory baseline is already high.


🔷 Real Case Example

A 62-year-old woman with diabetes came to MJRC with severe knee pain. She had undergone PRS treatment years earlier, and her MRI appeared normal — no meniscal tear, no major cartilage loss.

But her pain suddenly spiked. Her HbA1c was 10.2.

Metabolic imbalance amplified her alarmin response. Once we stabilised her metabolic status and reduced inflammatory load, her pain reduced significantly.

The knee was structurally normal. The biology was not.


🔷 The Metabolic Link: Why Diabetics Have Worse Flares

1. High glucose = more oxidative stress
This irritates cartilage and synovium.

2. Insulin resistance = immune overactivation

Your immune cells become more aggressive.

3. Poor resolution response

Inflammation starts — but doesn’t stop.

This is why many diabetics experience:

  • burning pain

  • night pain

  • sudden swelling

  • pain even at rest

These are chemical flares, not mechanical damage.


🔷 Why Your MRI Can Look “Normal” But You Still Hurt

Most diagnostic scans detect structure, not chemistry.

Alarmins affect:

  • synovial lining

  • cartilage cells

  • immune pathways

But these may not show up on:

  • X-ray

  • MRI

  • ultrasound

So many patients hear:

“Your scan is normal — nothing is wrong.”

Yet their pain continues because the problem is biochemical, not structural.


🔷 How We Diagnose Alarmin-Driven Knee Pain at MJRC

At Madras Joint Rejuvenation Centre, we evaluate both:

  • Mechanical causes (cartilage, meniscus, alignment)

  • Chemical causes (alarmins, metabolism, inflammation)

Our assessment includes:

  • metabolic profile (HbA1c, insulin resistance markers)

  • synovitis evaluation

  • inflammatory triggers

  • mechanical stress evaluation

  • gait and load analysis

This gives a complete picture, not a partial one.


🔷 Treatment: How We Calm Alarmins and Reduce Flares

We follow a stepwise scientific protocol:

1. Reduce metabolic load

  • stabilise blood sugar

  • improve insulin sensitivity

  • lower inflammatory baseline

2. Quiet the alarmin response

  • targeted supplements

  • structured anti-inflammatory nutrition

  • guided low-load exercise

3. Modulate joint biology

Using orthobiologics:

  • PRS (Platelet-Rich Serum)

  • PRASAD protocol

  • BMAC

  • SBE (Subchondral Biologic Enhancement)

These work best when metabolic inflammation is controlled.

4. Restore joint resilience

  • graded strengthening

  • neuromuscular activation

  • metabolic conditioning

This transforms the internal joint environment.


🔷 When Should You Seek Help?

If you experience:

  • knee pain without injury

  • pain at rest

  • sudden flare-ups

  • night pain

  • pain that doesn’t match your MRI findings

  • worsening after sugary meals

  • diabetes + knee pain

…your knee pain may be alarmin-driven, not mechanical.


🔷 Final Takeaway

Your knee isn’t just wearing out — it is signalling.

Alarmins are your joint’s distress signal.
Ignoring them means the cycle continues.
Understanding them gives you control over flare-ups.


🔷 Need a True Biologic Evaluation?

At Madras Joint Rejuvenation Centre, we specialise in evaluating knee pain using:

  • metabolic assessment

  • immune pathway analysis

  • mechanical load evaluation

  • orthobiologic treatment sequencing

If your pain is unpredictable or doesn’t match your scan, you may have alarmin-driven inflammation.

👉 Book a scientific knee evaluation at MJRC.
👉 Let’s calm the biology and restore your joint.

Contact links- E mail- drvenkatjoints@gmail.com

Clinic- https://share.google/if8xFKw1ntV5uby0z

The Scientific Evidence Behind Inflammation-First Knee Arthritis Care

  1. Scientific Basis of Inflammation-First Knee Arthritis Care

This page summarises the scientific evidence supporting an inflammation-first approach to knee osteoarthritis, as presented in the Inflammation Pillar Video. Each section corresponds directly to a key statement from the script, supported by peer-reviewed research.

1. Knee Arthritis Is Not Just Wear and Tear

Scientific Proof

Osteoarthritis is now recognised as a whole-joint inflammatory disease involving the synovium, cartilage, subchondral bone, ligaments, and infrapatellar fat pad.

Key References

  • Robinson WH et al., Nature Reviews Rheumatology – Osteoarthritis as an inflammatory disease
  • Berenbaum F, Osteoarthritis and Cartilage – Low-grade chronic inflammation in OA progression

Consensus

Mechanical damage alone does not explain pain severity or disease progression.


2. Inflammation Inside the Joint Drives Pain, Stiffness, and Progression

Scientific Proof

  • Synovitis strongly correlates with pain severity
  • Associated with effusion and stiffness
  • Predicts faster cartilage loss

Key References

  • Hill CL et al., Annals of the Rheumatic Diseases
  • Felson DT et al., Arthritis & Rheumatology

Consensus

Pain tracks inflammatory activity, not X-ray grade.


3. Two Patients With the Same X-Ray Can Have Very Different Pain

Scientific Proof

Radiographic severity correlates poorly with clinical symptoms.

Key References

  • Bedson J, Croft PR, Rheumatology
  • Hannan MT et al., Arthritis & Rheumatism

Consensus

Imaging underestimates biological disease activity.


4. Exercise Improves Support, Not Inflammation

Scientific Proof

  • Improves muscle strength and neuromuscular control
  • Does not suppress synovial cytokines when inflammation is active

Key References

  • Henriksen M et al., Osteoarthritis and Cartilage
  • Baker KR et al., Arthritis Care & Research

Consensus

Exercise is necessary but biologically insufficient when inflammation is uncontrolled.


5. Why Patients Plateau Despite Good Physiotherapy

Scientific Proof

  • Active synovitis predicts poor rehabilitation response
  • Associated with pain flares after loading
  • Reduces tolerance to strengthening

Key References

  • Scanzello CR et al., Clinical Orthopaedics and Related Research
  • Schaible HG, Nature Reviews Rheumatology

Consensus

Plateaus are biological, not motivational failures.


6. Painkillers Suppress Symptoms, Not Disease Biology

Scientific Proof

  • NSAIDs reduce pain temporarily
  • Do not halt cartilage degeneration
  • Do not modify disease progression

Key References

  • Zhang W et al., OARSI Guidelines
  • Hochberg MC et al., Arthritis Care & Research

Consensus

Symptom relief does not equal disease control.


7. Sequence Matters: Calm Inflammation Before Strengthening

Scientific Proof

  • Reducing inflammatory load improves pain thresholds
  • Improves exercise tolerance
  • Enhances functional outcomes

Key References

  • Atukorala I et al., Arthritis Research & Therapy
  • Bennell KL et al., British Journal of Sports Medicine

Consensus

Biological readiness determines rehabilitation success.


8. Joint Preservation Focuses on Biology, Not Just Mechanics

Scientific Proof

Modern OA management emphasises early biological modulation, load management, and individualised treatment sequencing.

Key References

  • Loeser RF et al., Osteoarthritis and Cartilage
  • Hunter DJ, The Lancet

Consensus

Joint preservation is proactive, not passive.


9. Inflammation Is Treatable

Scientific Proof

  • Inflammation in OA is measurable
  • Inflammation is modifiable
  • Inflammation is clinically meaningful

Key References

  • Mathiessen A, Conaghan PG, Arthritis Research & Therapy
  • Scanzello CR, Goldring SR, Arthritis & Rheumatology

Consensus

Osteoarthritis inflammation is manageable, not inevitable.

See the video here -https://youtu.be/IJFPdKUwpc0?si=5lN4781-zEmo3Xk0

FAQ’s

Q: Is knee osteoarthritis only caused by wear and tear?

A: No. Current research shows osteoarthritis is a whole-joint inflammatory disease. Mechanical wear alone does not explain pain severity or progression.

Q: Why does knee pain not match X-ray findings?

A: Pain correlates more strongly with synovial inflammation than with radiographic cartilage loss. X-rays underestimate biological disease activity.

Q: Does exercise reduce inflammation in knee arthritis?

A: Exercise improves strength and support but does not reliably suppress active synovial inflammation when it is present.

Q: Why do some patients plateau despite physiotherapy?

A: Active inflammation sensitises pain pathways and limits tolerance to loading, leading to biological—not motivational—plateaus.

Q: Are painkillers disease-modifying in knee arthritis?

A: No. NSAIDs reduce symptoms temporarily but do not alter the underlying disease process or progression.

Knee arthritis cellular therapy India

Knee arthritis cellular therapy India -Dr.A.K.Venkatachalam

Knee arthritis cellular therapy India Dr.A.K.Venkatachalam is shown here. The patient is a 72 year old male who had undergone two previous treatments with bone marrow cellular therapy and arthroscopic washout and lavage. Now he has chosen to undergo fat derived cellular therapy because fat is better than bone marrow as it contains more signalling cells. If you want this procedure, email drvenkat@kneeindia.com.

BMC treatment Knee osteoarthritis Chennai

BMC treatment knee arthritis India

BMC treatment knee arthritis India. Do you want to know what this is all about? Listen to this video.

Listen to this patient’s testimonial here after understanding the above explanation.

If you want to be considered for this treatment, schedule an appointment with the doctor in Chennai by mail at this id. drvenkat@kneeindia.com. Visit www.orthobiologicsurgeryindia.com for more information.

Knee Cartilage repair India

Evidence stem cell treatment Chennai

Last night a doctor asked me for the longest duration of evidence stem cell treatment Chennai in my practiceCases of OA knee from 2004 on whom I performed first generation cell procedures constitute this evidence. I started doing first generation biological procedure by arthroscopy in 2004. There are several patients with early knee osteoarthritis who were able to avoid or postpone a knee replacement by several years. Subsequently they either got a further biological treatment or went in for knee replacement. See the videos below for this evidence. This evidence pre dates some of the stem cell clinics in the US who reported their first cases in 2008. Although it was done by arthroscopy, the scientific basis is the same: of getting the body’s cells to repair the body. If you need more evidence for stem cells, please see the FAQ section.

  1. The first video recorded in 2013 is that of a man who underwent a micro fracture of the knee in 2006. His knee pain was relieved. Only in the year 2013 he had some recurrence and this was further treated by a PRP injection. He has not had any problem in the last two years. He has been able to avoid a knee replacement so far.
    Watch the video from 0.48 to 1.24 for the relevant portion. He says that earlier he had severe knee pain and was unable to stand for even five minutes. He underwent a micro fracture procedure at DAE hospital and this relieved him of pain. Micro fracture is a first generation stem cell procedure. It consists of harvesting cells from the base of the damaged cartilage in the knee. Underlying cells flow into the area and organize to form a super clot. These go on to mature to form a covering layer of fibro cartilage. Pain relief results which can last for several years. The MRI picture is also captured in the video at 1.38 fleetingly.

2. In the second video, a lady underwent a micro fracture of her left knee in the year 2007. Her knee pain began from 2005. She was able to obtain good pain relief and function which lasted up to 2011. She finally decided to get  knee replacement in 2013 which is when this video was recorded. So she was able to manage for six years with a first generation cell procedure known as micro fracture. Watch from 4.16 to 6.37. This video is in Tamil.

 

So one can note that I have followed up my patients over the years. So seven years is the longest duration  of follow up with cell therapy with in my practice with the first generation technique. This constitutes proof. In fact, this news was also published in The Hindu, an English news paper in 2004 and 2005.