C5–C6 Disc Proteoglycan Loss

Intervertebral discs are cushions between the vertebrae that allow flexibility and absorb shock. Each disc has a gel-like core called the nucleus pulposus, rich in proteoglycans—molecules that attract and retain water, keeping the disc plump and resilient. Over time, or under stress (injury, poor posture, genetics), proteoglycans break down and water content falls. At the C5–C6 level in the neck, this loss—called proteoglycan depletion—leads to disc thinning, reduced flexibility, increased friction, and pain, sometimes causing nerve irritation (radiculopathy) or spinal cord compression (myelopathy).

Anatomy of the C5–C6 Intervertebral Disc Proteoglycan Complex

The C5–C6 disc sits between the fifth and sixth cervical vertebrae in the neck. It acts as a shock absorber and allows smooth movement between these two bones. Understanding its anatomy is essential for appreciating how proteoglycan loss leads to disc degeneration.

1. Structure and Location
   The C5–C6 disc is a fibrocartilaginous joint composed of an outer annulus fibrosus and an inner nucleus pulposus. The annulus has concentric lamellae of collagen fibers that resist twisting, while the gelatinous nucleus rich in proteoglycans provides cushion under compressive loads. Located just below the C5 vertebral body and above C6, it contributes to roughly 50% of cervical spine flexion and extension.

2. Origin and Insertion
   Discs do not “originate” or “insert” like muscles; rather, the annulus attaches peripherally to the superior and inferior vertebral endplates of C5 and C6. These attachments are secured by Sharpey’s fibers that anchor collagen lamellae into the bony endplates, preventing disc slippage and maintaining alignment during neck movements.

3. Blood Supply
   Healthy intervertebral discs are largely avascular. Nutrients reach the nucleus pulposus and inner annulus by diffusion through the cartilaginous endplates from capillaries in the adjacent vertebral bodies. A small peripheral plexus at the outer annulus carries minimal blood flow, enough to nourish outer annular cells but not the central nucleus.

4. Nerve Supply
   Sensory innervation of the C5–C6 disc is provided by the sinuvertebral (recurrent meningeal) nerves, which enter the outer one-third of the annulus fibrosus. These nerves convey pain signals when the annulus is torn or inflamed. There is no direct nerve supply to the nucleus pulposus under normal conditions.

5. Functions of the C5–C6 Disc

   • Shock Absorption: Proteoglycan-rich nucleus resists compression, protecting vertebrae.

   • Load Distribution: Evenly spreads mechanical forces across endplates.

   • Flexibility: Allows bending and rotation of the cervical spine.

   • Height Maintenance: Preserves intervertebral space, preventing nerve root compression.

   • Joint Stability: Collagen fibers of the annulus limit excessive movement.

   • Nutrient Exchange: Endplates facilitate diffusion of oxygen and glucose into disc cells.

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Types of Proteoglycan Loss at C5–C6

Proteoglycans—aggrecan molecules bearing negatively charged glycosaminoglycan chains—retain water to maintain disc height. Loss can be classified by severity and pattern:

1. Mild Dehydration: Early loss of water-binding capacity without structural collapse.

2. Moderate Degeneration: Reduced disc height, fissuring in annulus, slight bulging.

3. Severe Degeneration: Advanced dehydration, disc space narrowing, osteophyte formation.

4. Focal Proteoglycan Deficiency: Localized patches of low proteoglycan density, leading to disc herniation.

5. Diffuse Proteoglycan Depletion: Uniform loss throughout nucleus, causing global stiffness.

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Causes of C5–C6 Disc Proteoglycan Loss

1. Aging: Natural breakdown of proteoglycans over decades reduces water content.

2. Genetic Predisposition: Variants in aggrecan gene (ACAN) accelerate matrix breakdown.

3. Smoking: Nicotine impairs blood diffusion, reducing nutrient delivery to disc cells.

4. Obesity: Excess axial load increases mechanical stress on C5–C6 segment.

5. Repetitive Microtrauma: Cumulative neck movements in certain occupations wear down disc matrix.

6. Acute Trauma: Whiplash or falls can tear annular fibers and disrupt proteoglycan-rich nucleus.

7. Poor Posture: Forward head posture increases sustained compression at lower cervical levels.

8. Diabetes Mellitus: Advanced glycation end products stiffen proteoglycans and impair repair.

9. Inflammatory Cytokines: Elevated interleukin-1β and TNF-α promote matrix metalloproteinases that degrade proteoglycans.

10. Disc Ischemia: Endplate calcification limits nutrient diffusion, starving disc cells.

11. Occupational Vibration: Use of jackhammers or heavy machinery transmits vibratory forces damaging matrix.

12. Sedentary Lifestyle: Lack of movement impairs nutrient exchange via endplate diffusion.

13. Autoimmune Reaction: Rarely, autoantibodies target disc proteins, triggering degradation.

14. Radiation Exposure: Therapeutic or accidental radiation can damage disc cell DNA and function.

15. Hormonal Changes: Post-menopausal estrogen decline correlates with decreased proteoglycan synthesis.

16. Nutritional Deficiencies: Lack of vitamin C or manganese impairs collagen and proteoglycan synthesis.

17. Oxidative Stress: Reactive oxygen species from metabolic processes degrade matrix components.

18. Matrix Metalloproteinase Imbalance: Overexpression of MMP-3 and MMP-13 accelerates proteoglycan breakdown.

19. Obstructive Sleep Apnea: Intermittent hypoxia may impair disc cell metabolism.

20. Spinal Instability: Facet joint laxity increases motion at C5–C6, stressing proteoglycan matrix.

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Symptoms Associated with C5–C6 Proteoglycan Loss

Patients with significant proteoglycan depletion at C5–C6 may experience:

1. Neck Pain: Dull ache localized at the lower cervical region.

2. Stiffness: Reduced range of motion, especially on extension.

3. Radiculopathy: Pain radiating into the shoulder or arm along C6 dermatome.

4. Paresthesia: Tingling or “pins and needles” in the thumb and index finger.

5. Muscle Weakness: Weakness in biceps or wrist extensors.

6. Headaches: Referred pain causing occipital headaches.

7. Crepitus: Clicking or popping sensations during neck movement.

8. Balance Issues: Less common, but severe degeneration may affect proprioceptive feedback.

9. Muscle Spasms: Involuntary contraction of neck muscles.

10. Localized Tenderness: Pain on palpation over C5–C6 spinous process.

11. Reduced Disc Height: Clinically observed as loss of cervical lordosis.

12. Myelopathy (Severe): Spinal cord compression signs such as gait disturbance.

13. Reflex Changes: Altered biceps or brachioradialis reflexes.

14. Neck Instability Sensation: Feeling of “giving way” when turning head.

15. Difficulty Swallowing: If large osteophytes press on esophagus.

16. Ear Pain (Otalgia): Referred pain sometimes felt around the ear.

17. Sleep Disturbance: Discomfort at night due to constant pain.

18. Radiographic Findings: Symptoms may correlate with imaging changes even if mild.

19. Fatigue: Chronic pain leading to overall tiredness.

20. Psychological Impact: Anxiety or depression secondary to persistent pain.

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Diagnostic Tests for C5–C6 Disc Proteoglycan Loss

A. Physical Examination

1. Inspection: Observing cervical alignment and lordosis.

2. Palpation: Checking for point tenderness over C5–C6.

3. Range of Motion (ROM): Measuring flexion, extension, lateral bending.

4. Spurling’s Test: Applying axial compression with neck rotation to reproduce radicular pain.

5. Lhermitte’s Sign: Neck flexion triggering electric shock–like sensation, indicating myelopathy.

6. Cervical Distraction Test: Lifting head gently to see if pain is relieved.

B. Manual Tests

7. Manual Muscle Testing: Assessing strength of biceps (C5–C6) and wrist extensors (C6).

8. Sensory Testing: Light touch and pinprick in C6 dermatome.

9. Reflex Assessment: Checking biceps and brachioradialis reflexes.

10. Provocative Compression: Gentle compression to elicit nerve root pain.

11. Neck Flexor Endurance Test: Holding chin tuck to assess deep neck flexor function.

12. Joint Position Sense: Testing patient’s ability to reposition head after movement.

C. Laboratory and Pathological Tests

13. Erythrocyte Sedimentation Rate (ESR): Rule out inflammatory spondylitis.

14. C-Reactive Protein (CRP): Marker of systemic inflammation.

15. Complete Blood Count (CBC): Identify infection or leukocytosis.

16. HLA-B27 Testing: If ankylosing spondylitis is suspected.

17. Serum Metabolic Panel: Check calcium, phosphate for bone health.

18. Disc Biopsy (Rare): Histological evaluation of proteoglycan content.

D. Electrodiagnostic Studies

19. Electromyography (EMG): Detect denervation in C6-innervated muscles.

20. Nerve Conduction Velocity (NCV): Assess speed of impulses along C6 nerve root.

21. Somatosensory Evoked Potentials (SSEPs): Evaluate dorsal column function.

22. Motor Evoked Potentials (MEPs): Check corticospinal tract integrity.

23. F-Wave Studies: Examine proximal nerve segments for root involvement.

24. H-Reflex Testing: Evaluate reflex arc, especially C6–C7.

E. Imaging Tests

25. Plain Radiographs (X-ray): View disc space narrowing, osteophytes.

26. Magnetic Resonance Imaging (MRI): Gold standard for visualizing proteoglycan loss as decreased T2 signal in nucleus.

27. Computed Tomography (CT): Detailed bone assessment of endplates and osteophytes.

28. CT Myelography: Combined CT with contrast to assess cord or root compression.

29. Discography: Injection of contrast into nucleus to provoke pain and outline fissures.

30. Ultrashort Echo Time MRI (UTE-MRI): Emerging technique to quantify proteoglycan content.

Non-Pharmacological Treatments

For each: what it is, why it helps, and how it works in simple terms.

1. Neck Stabilization Exercises

   • Description: Gentle isometric holds pressing your head lightly into your hands in different directions.

   • Purpose: Builds deep neck muscle strength to support the spine.

   • Mechanism: Activates small stabilizer muscles, reducing load on the disc by sharing weight across muscles.

2. Cervical Traction

   • Description: Using a device or hands to gently pull the head upward.

   • Purpose: Creates space between vertebrae.

   • Mechanism: Reduces pressure inside the disc, allowing nutrients to flow back in.

3. Posture Correction Training

   • Description: Learning and practicing proper head-over-shoulder alignment.

   • Purpose: Minimizes undue stress on the C5–C6 disc.

   • Mechanism: Keeps weight centered over the spine, preventing forward head tilt.

4. Heat Therapy

   • Description: Warm packs applied to the neck.

   • Purpose: Relaxes tight muscles and reduces pain.

   • Mechanism: Increases blood flow, improving tissue flexibility.

5. Cold Therapy

   • Description: Ice packs for 15–20 minutes.

   • Purpose: Decreases swelling and numbs pain.

   • Mechanism: Constricts blood vessels, reducing inflammation.

6. Manual Therapy (Chiropractic/Massage)

   • Description: Hands-on adjustment or muscle release by a licensed practitioner.

   • Purpose: Increases mobility and eases muscle tension.

   • Mechanism: Restores joint motion, improves circulation, and breaks up adhesions.

7. Ultrasound Therapy

   • Description: Sound waves applied via a handheld device.

   • Purpose: Heats deep tissues without heat packs.

   • Mechanism: Promotes collagen alignment and nutrient exchange.

8. Electrical Stimulation (TENS)

   • Description: Low-voltage electrical current through skin pads.

   • Purpose: Blocks pain signals.

   • Mechanism: Activates “gate control” in nerves, reducing pain perception.

9. Aquatic Therapy

   • Description: Exercises performed in a warm pool.

   • Purpose: Reduces joint load while strengthening.

   • Mechanism: Buoyancy offloads the spine; water resistance builds muscle evenly.

10. Cervical Collar (Soft) Use

    • Description: A padded neck brace worn briefly.

    • Purpose: Limits painful movement during flare-ups.

    • Mechanism: Stabilizes the neck, preventing harmful motions.

11. Dry Needling

    • Description: Thin needles into trigger points.

    • Purpose: Relieves muscle knots.

    • Mechanism: Disrupts tight bands, improving blood flow.

12. Acupuncture

    • Description: Traditional needle therapy.

    • Purpose: Eases pain and inflammation.

    • Mechanism: Stimulates nerves to release endorphins and improve circulation.

13. Yoga for Neck Health

    • Description: Gentle poses with neck focus.

    • Purpose: Improves flexibility and posture.

    • Mechanism: Stretches neck muscles, balances muscular tension.

14. Pilates

    • Description: Core-strengthening exercises.

    • Purpose: Builds trunk support for cervical spine.

    • Mechanism: Engages deep core muscles, reducing cervical load.

15. Ergonomic Workplace Adjustments

    • Description: Screen at eye level; chair with good lumbar support.

    • Purpose: Prevents forward head posture.

    • Mechanism: Maintains natural cervical curve during work.

16. Mindfulness Meditation

    • Description: Focused breathing and awareness.

    • Purpose: Reduces pain-related stress.

    • Mechanism: Modulates brain’s pain-processing centers.

17. Biofeedback

    • Description: Sensors to monitor muscle tension.

    • Purpose: Teaches muscle relaxation.

    • Mechanism: Real-time feedback helps you consciously decrease tension.

18. Progressive Muscle Relaxation

    • Description: Alternately tensing/relaxing muscle groups.

    • Purpose: Lowers overall muscle tightness.

    • Mechanism: Decreases sympathetic (stress) response.

19. Tai Chi

    • Description: Slow, flowing movements.

    • Purpose: Enhances balance and neck control.

    • Mechanism: Improves proprioception and muscular coordination.

20. Cervical Flexion-Extension Stretching

    • Description: Slowly nodding head up/down.

    • Purpose: Restores disc nutrition through movement.

    • Mechanism: “Pumps” fluids into the disc.

21. Cervical Side-Bending and Rotation Stretches

    • Description: Gentle tilts and turns.

    • Purpose: Increases range of motion.

    • Mechanism: Stretches ligament and muscle fibers around the disc.

22. Isometric Shoulder Blade Squeezes

    • Description: Pinching shoulder blades together.

    • Purpose: Strengthens upper back support.

    • Mechanism: Offloads the cervical spine by reinforcing scapular stability.

23. Neck Pillows

    • Description: Ergonomically shaped pillows.

    • Purpose: Maintains curve during sleep.

    • Mechanism: Supports cervical lordosis, reducing overnight stress.

24. Soft Tissue Mobilization

    • Description: Therapist-applied pressure and stroking.

    • Purpose: Breaks up adhesions and scar tissue.

    • Mechanism: Improves tissue glide and blood flow.

25. Infrared Light Therapy

    • Description: Infrared lamp directed at the neck.

    • Purpose: Deep-tissue warming.

    • Mechanism: Enhances cellular repair and circulation.

26. Ergonomic Driving Adjustments

    • Description: Seat angled to support lumbar and neck.

    • Purpose: Prevents neck strain on long drives.

    • Mechanism: Keeps spine neutral, distributing forces evenly.

27. Craniosacral Therapy

    • Description: Gentle rhythmic manipulation of skull and spine.

    • Purpose: Eases cerebrospinal fluid flow and tension.

    • Mechanism: May reduce dural tension affecting the disc.

28. Functional Movement Training

    • Description: Practice lifting, bending safely.

    • Purpose: Prevents harmful loading of the neck.

    • Mechanism: Teaches body mechanics that protect the disc.

29. Traction Pillow

    • Description: Inflatable neck pillow for home traction.

    • Purpose: Provides mild sustained distraction.

    • Mechanism: Slightly separates vertebrae, promoting rehydration.

30. Weighted Neck Exercises

    • Description: Gentle head movements with light weights or bands.

    • Purpose: Builds neck muscle endurance.

    • Mechanism: Strengthens muscles that share the load with discs.

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Pharmacological Treatments

For each: typical dosage, drug class, timing, common side effects.

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Dietary Molecular Supplements

Dosage, primary function, mechanism in the disc.

1. Glucosamine Sulfate (1 500 mg/day)

   • Function: Supports cartilage building.

   • Mechanism: Provides raw building blocks for proteoglycan synthesis.

2. Chondroitin Sulfate (1 200 mg/day)

   • Function: Helps retain water in discs.

   • Mechanism: Inhibits enzymes that break down proteoglycans.

3. Collagen Peptides (10 g/day)

   • Function: Supplies amino acids for disc matrix.

   • Mechanism: Stimulates fibroblasts to make collagen and proteoglycans.

4. MSM (Methylsulfonylmethane) (1 000–3 000 mg/day)

   • Function: Reduces inflammation.

   • Mechanism: Donates sulfur for connective tissue repair.

5. Hyaluronic Acid (100 mg/day)

   • Function: Improves disc hydration.

   • Mechanism: Attracts and holds water in extracellular matrix.

6. Omega-3 Fatty Acids (1–3 g/day EPA/DHA)

   • Function: Anti-inflammatory support.

   • Mechanism: Shifts cell balance from pro- to anti-inflammatory signals.

7. Curcumin (500 mg twice daily)

   • Function: Natural anti-inflammatory.

   • Mechanism: Inhibits NF-κB pathway that triggers inflammation.

8. Vitamin D₃ (1 000–2 000 IU/day)

   • Function: Bone and muscle health.

   • Mechanism: Regulates calcium and promotes matrix formation.

9. Vitamin C (500 mg twice daily)

   • Function: Collagen synthesis.

   • Mechanism: Cofactor for pro-collagen hydroxylation enzymes.

10. Magnesium (300 mg/day)

• Function: Muscle relaxation and metabolic support.

• Mechanism: Acts as cofactor in ATP production for cell repair.

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Advanced Drug Therapies

Including bisphosphonates, regenerative, viscosupplements, stem cell drugs.

1. Alendronate (Bisphosphonate, 70 mg weekly)

   • Function: Slows bone remodeling around disc.

   • Mechanism: Inhibits osteoclasts, stabilizing vertebral endplates.

2. Zoledronic Acid (Bisphosphonate, 5 mg IV yearly)

   • Function: Long-term bone support.

   • Mechanism: Potent osteoclast inhibition reduces microfractures.

3. Pentosan Polysulfate (Viscosupplement, 100 mg SC weekly)

   • Function: Improves disc hydration.

   • Mechanism: Mimics glycosaminoglycans to attract water.

4. Hyaluronan Injection (Viscosupplement, 2 mL esp.)

   • Function: Increases local lubrication.

   • Mechanism: Boosts extracellular matrix viscosity.

5. Growth Factor Cocktail (Regenerative, epidural)

   • Function: Stimulates matrix repair.

   • Mechanism: Delivers PDGF/VEGF to promote cell proliferation.

6. Platelet-Rich Plasma (Regenerative, autologous 2–4 mL)

   • Function: Heals disc tissue.

   • Mechanism: Platelet growth factors recruit repair cells.

7. BMP-7 (Regenerative, 0.5 mg disc implant)

   • Function: Encourages new matrix formation.

   • Mechanism: Bone morphogenetic protein induces proteoglycan synthesis.

8. Stem Cell Suspension (Mesenchymal, 1×10⁶ cells)

   • Function: Rebuilds disc matrix.

   • Mechanism: Differentiates into nucleus pulposus–like cells.

9. Exosome Therapy (Stem cell-derived, 100 µg)

   • Function: Modulates inflammation and repair.

   • Mechanism: Delivers microRNAs to shift cell behavior.

10. Gene Therapy (Aggrecan gene plasmid)

• Function: Replenishes proteoglycan production.

• Mechanism: Cells take up plasmid and synthesize new aggrecan.

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 Surgical Options

1. Anterior Cervical Discectomy

2. Anterior Cervical Discectomy and Fusion (ACDF)

3. Cervical Disc Arthroplasty (Disc Replacement)

4. Posterior Cervical Laminoforaminotomy

5. Posterior Cervical Laminectomy

6. Foraminotomy with Microscopic Decompression

7. Posterior Facetectomy

8. Cervical Corpectomy

9. Minimally Invasive Endoscopic Discectomy

10. Anterior Plate and Screw Fixation

Each procedure removes or replaces the damaged disc, relieves nerve compression, and stabilizes the spine using implants or bone grafts as needed.

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Prevention Strategies

1. Maintain Good Posture – Keep head balanced over shoulders.

2. Ergonomic Workstation – Screen at eye level, chair with support.

3. Regular Exercise – Strengthen core and neck muscles.

4. Healthy Weight – Reduces spinal load.

5. Quit Smoking – Smoking accelerates disc degeneration.

6. Balanced Diet – Nutrients for disc health (vitamins C, D, protein).

7. Proper Lifting Technique – Bend knees, keep back straight.

8. Frequent Breaks – Avoid prolonged static postures.

9. Stay Hydrated – Supports disc hydration.

10. Stress Management – Lowers muscle tension around neck.

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When to See a Doctor

Seek medical attention if you experience:

• Numbness or tingling in arms or hands

• Weakness in grip or arm muscles

• Loss of bladder or bowel control (emergency!)

• Severe, unrelenting neck pain not relieved by rest or medications

• Pain radiating down the arm beyond occasional discomfort

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Frequently Asked Questions

1. What causes proteoglycan loss in C5–C6 discs?
   Age, genetics, repeated stress, poor posture, smoking, and previous neck injuries accelerate breakdown of proteoglycans, leading to disc drying and degeneration.

2. Is C5–C6 proteoglycan loss reversible?
   Early stages may respond to conservative treatments that improve hydration and matrix repair, but advanced loss is permanent—focus shifts to symptom management and preventing progression.

3. How long does recovery take with non-surgical care?
   Most people improve within 6–12 weeks of consistent therapy and exercise, though chronic cases may require ongoing management.

4. Can supplements like glucosamine really help?
   Some studies show modest benefit in supporting proteoglycan production, but they work best combined with physical therapy and healthy habits.

5. When is surgery recommended?
   If severe nerve symptoms (weakness, numbness) persist after 8–12 weeks of conservative care, or if spinal cord compression signs appear, surgical options are considered.

6. Are steroid injections safe?
   Epidural steroids can reduce inflammation and pain but carry risks like infection or temporary blood sugar rise; use is limited to a few injections per year.

7. Will weight loss improve my neck disc health?
   Yes—less body weight decreases overall spinal load and may slow further degeneration.

8. What exercises should I avoid?
   High-impact activities, heavy overhead lifting, or deep neck flexion/extension under load can worsen disc stress—stick to guided programs.

9. How do I sleep with a degenerated C5–C6 disc?
   Use a supportive, contoured pillow and sleep on your back or side with minimal neck rotation to maintain neutral alignment.

10. Is MRI necessary to diagnose proteoglycan loss?
    MRI best visualizes water content and disc height, confirming proteoglycan depletion—X-rays alone can miss early changes.

11. Can massage worsen my condition?
    Gentle therapeutic massage helps, but deep tissue or aggressive manipulation should be avoided without professional guidance.

12. What lifestyle changes help most?
    Quitting smoking, improving posture, staying active, and maintaining healthy weight have the biggest long-term impact.

13. Are stem cell treatments approved?
    Some early-phase studies show promise, but most stem cell therapies for discs remain experimental and are not yet standard care.

14. How do I manage flare-ups of neck pain?
    Rest briefly, apply ice/heat, use a soft collar for short periods, and resume gentle mobility exercises as pain allows.

15. Can I continue working with C5–C6 degeneration?
    Many patients adapt with ergonomic changes, posture training, and regular breaks—most office-based work is possible with proper adjustments.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team Rxharun and reviewed by the Rx Editorial Board Members

Last Updated: May 11, 2025.

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