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Understanding Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Medically Reviewed By:

Dr. Chaz Fausel, MD

Dr. Chaz Fausel is a Denver-based interventional orthopedics specialist and Regenexx educator, trained at Emory and the Centeno-Schultz Clinic.

Nonsteroidal anti-inflammatory Drugs (NSAIDs) are widely used medications that may help manage everyday discomforts such as headaches, muscle aches, and joint pain, and are often recommended for chronic conditions involving inflammation, such as arthritis. Many people take NSAIDs for their quick relief and versatility, making them a popular choice in both short-term and ongoing pain management.

However, understanding NSAIDs is essential for making informed decisions about their use, potential benefits, and risks. The following sections will explore how NSAIDs work when they’re most useful, and what to consider for safe and effective use.

Defining NSAIDs

NSAIDs are a class of medications commonly used to reduce pain, lower fever, and ease inflammation. They include both over-the-counter options and prescription formulations. Common over-the-counter NSAIDs include ibuprofen (sold as Motrin and Advil) and naproxen (sold as Aleve). 

Prescription options include celecoxib (Celebrex), diclofenac (Voltaren), and etodolac (Lodine), among others. These medications are frequently used to manage pain from injuries, arthritis, and various chronic inflammatory conditions.

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How Does It Work?

NSAIDs work by targeting the body’s inflammatory response, often a source of pain and discomfort in conditions like arthritis or injury-related pain. Their primary action is to inhibit cyclooxygenase (COX) enzymes, which play a significant role in inflammation and pain. There are two main types of COX enzymes: COX-1 and COX-2.

COX-1 enzymes help maintain the protective lining of the stomach and intestines, while COX-2 enzymes are primarily active during inflammation. When tissue is damaged or inflamed, COX-2 enzymes produce prostaglandins that increase blood flow, swelling, and pain in the affected area. By blocking COX enzymes—particularly COX-2, NSAIDs reduce prostaglandin production, helping relieve pain and reduce swelling.

Common Conditions That Respond To NSAIDs Treatment

NSAIDs are commonly used to reduce pain, inflammation, and swelling in a variety of musculoskeletal, joint, ligament, and tendon-related conditions, helping to improve mobility and comfort. Here are the conditions:

  • Meniscal Cyst: A meniscal cyst is a fluid-filled sac that forms near the knee joint, often due to a meniscus tear. It may cause swelling, knee pain, and stiffness, particularly with movement. Symptoms can vary based on the cyst’s size and location. Read More About Meniscal Cyst.
  • Shoulder Instability: Shoulder instability occurs when the shoulder joint becomes loose or prone to dislocation due to weakened or damaged ligaments. It may cause pain, weakness, and a feeling of the shoulder slipping out of place, often worsening with overhead or repetitive arm movements. Read More About Shoulder Instability.
  • Facet Cysts: A facet cyst is a fluid-filled sac that develops in the spine’s facet joint, often due to degeneration. Depending on size and location, it may cause localized back pain, nerve compression, or radiating symptoms such as numbness or weakness. Read More About Facet Cysts.
  • Slipped Discs: A slipped disc, or herniated disc, occurs when the soft inner portion of a spinal disc pushes through its outer layer. This may irritate nearby nerves, causing pain, numbness, or weakness in the back, neck, or limbs, depending on the location of the herniation. Read More About Slipped Discs.
  • Scoliosis: Scoliosis is a condition characterized by an abnormal sideways curvature of the spine. It may cause uneven shoulders, back pain, and postural changes. Severity varies, with some cases leading to mobility limitations or discomfort, especially if the curvature progresses over time. Read More About Scoliosis.
  • Sports Hernia: A sports hernia, or athletic pubalgia, is a soft tissue injury in the groin area caused by repetitive stress or sudden movements. It may lead to chronic groin pain, weakness, and discomfort, especially during twisting motions or intense physical activity. Read More About Sports Hernia.
  • Intersection Syndrome: Intersection syndrome is an overuse condition affecting the forearm and wrist, caused by friction between crossing tendons. It may lead to pain, swelling, and tenderness on the back of the wrist often worsening with repetitive hand or wrist movements. Read More About Intersection Syndrome.
  • Osteitis Pubis: Osteitis pubis is an inflammation of the pubic symphysis, the joint at the front of the pelvis. It may cause groin pain, stiffness, and difficulty with activities such as walking, running, or changing direction, often worsening with repetitive movements. Read More About Osteitis Pubis.
  • Morton’s Neuroma: Morton’s neuroma is a painful condition caused by the thickening of the tissue around a nerve in the ball of the foot, often between the third and fourth toes. It can lead to tingling, burning, or a feeling of stepping on a pebble. Read More About Morton’s Neuroma.
  • Slipping Rib Syndrome: Slipping rib syndrome occurs when the lower ribs move excessively due to weakened or loose ligaments, leading to pain, tenderness, and a popping sensation in the chest or upper abdomen. Symptoms may worsen with certain movements or deep breathing. Read More About Slipping Rib Syndrome.
  • Ankle Osteoarthritis: Ankle osteoarthritis occurs when the cartilage in the ankle joint wears down over time, leading to pain, stiffness, swelling, and reduced mobility. Symptoms may worsen with weight-bearing activities, potentially affecting balance and daily movement. Read More About Ankle Osteoarthritis.
  • Toe Osteoarthritis: Toe osteoarthritis occurs when the cartilage in the toe joints breaks down over time, leading to pain, stiffness, swelling, and reduced mobility. It may worsen with activity, making walking, bending, or wearing certain shoes uncomfortable. Read More About Toe Osteoarthritis.
  • Hip Osteoarthritis: Hip osteoarthritis occurs when the cartilage in the hip joint gradually wears down, leading to pain, stiffness, and reduced range of motion. Symptoms may worsen with movement or weight-bearing activities, potentially affecting mobility and daily function. Read More About Hip Osteoarthritis.
  • Knee Osteoarthritis: Knee osteoarthritis occurs when the cartilage in the knee joint wears down over time, leading to pain, stiffness, swelling, and reduced mobility. Symptoms may worsen with activity, potentially affecting daily movements such as walking or climbing stairs. Read More About Knee Osteoarthritis.
  • Thumb Arthritis: Thumb arthritis, or basal joint arthritis, occurs when the cartilage in the thumb’s base joint wears down, leading to pain, stiffness, and reduced grip strength. Symptoms may worsen with pinching or grasping movements, affecting daily activities. Read More About Thumb Arthritis.
  • TMJ Syndrome: TMJ syndrome, or temporomandibular joint disorder, occurs when dysfunction in the jaw joint causes pain, stiffness, clicking, or difficulty chewing. Symptoms may also include headaches, ear pain, or jaw locking, often worsening with jaw movement or stress. Read More About TMJ Syndrome.
  • Rotator Cuff Tears: A rotator cuff tear occurs when one or more tendons in the shoulder are partially or fully torn due to injury or degeneration. It may cause pain, weakness, and limited range of motion, often worsening with overhead movements or lifting. Read More About Rotator Cuff Tears.
  • Shoulder Labrum Tears: A shoulder labrum tear occurs when the cartilage ring surrounding the shoulder socket is damaged due to injury or repetitive strain. It may cause pain, instability, clicking sensations, and reduced range of motion, especially during overhead or rotational movements. Read More About Shoulder Labrum Tears.
  • Shoulder Osteoarthritis: Shoulder osteoarthritis occurs when the cartilage in the shoulder joint wears down over time, leading to pain, stiffness, swelling, and reduced range of motion. Symptoms may worsen with movement, potentially affecting daily activities and arm function. Read More About Shoulder Osteoarthritis.
  • Bulging Discs: A bulging disc occurs when a spinal disc extends beyond its normal space without rupturing. Depending on the affected area, it may cause localized pain or nerve compression, leading to numbness, tingling, or weakness in the back, neck, or limbs. Read More About Bulging Discs.
  • Herniated Discs: A herniated disc occurs when the soft inner portion of a spinal disc pushes through its outer layer, potentially compressing nearby nerves. Depending on the affected area, this may cause pain, numbness, tingling, or weakness in the back, neck, or limbs. Read More About Herniated Discs.
  • Spinal Stenosis: Spinal stenosis is when the spinal canal narrows, putting pressure on the spinal cord or nerves. It may cause pain, numbness, tingling, or weakness in the back, legs, or arms, often worsening with prolonged standing or walking. Read More About Spinal Stenosis.
  • Spondylolysis: Spondylolysis is a stress fracture or defect in the vertebra, most commonly in the lower back. It may cause localized pain, stiffness, and, in some cases, nerve irritation, often worsening with activity or prolonged standing. Read More About Spondylolysis.

Common Side Effects Of NSAIDs

While useful for managing pain and inflammation, NSAIDs come with a range of potential side effects, which can vary depending on dosage, frequency of use, and individual patient factors. Understanding these effects is essential for safe, informed use, particularly for individuals who rely on NSAIDs for long-term pain management.

  • Short-Term Side Effects:
    • Gastrointestinal Issues: NSAIDs can lead to stomach irritation, presenting as indigestion, nausea, or mild stomach discomfort. In some cases, even short-term use may cause more severe symptoms, such as stomach bleeding or ulcers.
    • Kidney Function: NSAIDs can affect kidney function by reducing blood flow to the kidneys. This effect is typically mild in short-term use but can be more pronounced in individuals with pre-existing kidney conditions.
    • Allergic Reactions: There are some individuals who may experience allergic reactions, such as hives, skin rashes, or, in rare cases, difficulty breathing. These reactions may occur shortly after taking NSAIDs.
  • Long-Term Side Effects:
    • Gastrointestinal Ulcers and Bleeding: Prolonged NSAID use increases the likelihood of significant gastrointestinal damage, including the formation of ulcers and a higher risk of stomach or intestinal bleeding. This risk is higher in older adults and in those who use NSAIDs frequently or at high doses.
    • Increased Cardiovascular Risk: Long-term NSAID use, especially at higher doses, has been linked to an increased risk of heart attack and stroke. This risk is notable with NSAIDs that inhibit both COX-1 and COX-2 enzymes, as COX-2 plays a role in heart health. Selective COX-2 inhibitors, such as celecoxib, were developed to help reduce gastrointestinal side effects, though they may still carry cardiovascular risks.
    • Kidney Damage: Chronic NSAID use can lead to kidney damage, particularly in individuals who have pre-existing kidney issues. Long-term use may impair the kidneys’ ability to filter waste, potentially contributing to chronic kidney disease (CKD).
    • Delayed Bone Healing: Emerging research indicates that NSAIDs may interfere with the body’s natural bone healing process. This effect appears linked to the body’s circadian rhythm, which regulates bone breakdown and repair.

Why This Happens

NSAIDs work by blocking inflammation, which is essential for managing pain. However, inflammation also plays a key role in the body’s natural healing response. During healing, inflammatory signals trigger cells to remove damaged tissue and initiate repair processes. Although healing occurs continuously, certain cellular activities, such as tissue regeneration, follow body rhythms that include phases of tissue breakdown and repair.

Research suggests that NSAID use—especially during the early stages of healing or before rest—can interfere with repair processes.  Studies have shown that NSAIDs may disrupt bone healing by blocking the inflammatory signals and prostaglandin pathways that are essential for tissue regeneration and remodeling.

This impact is significant for bone and soft tissue injuries, as inflammation is part of the body’s healing response. By reducing inflammation at critical times, NSAIDs may inadvertently impair healing, particularly when tissue repair is actively needed, such as after injuries or surgeries.

For these reasons, healthcare providers often advise against NSAID use during the early stages of healing, such as the first 4–6 weeks following procedures involving stem cell or platelet-rich plasma (PRP) treatments, where controlled inflammation is beneficial for optimal recovery.

Are There Alternatives To NSAIDs?

Several alternatives to NSAIDs may help manage pain and inflammation while supporting overall healing. Here are some commonly considered options:

  • Physical Therapy and Exercise: Structured physical therapy can reduce pain and improve function through strength training, flexibility exercises, and targeted movements that support joint health. Tailored exercise routines may enhance the range of motion and relieve pain without medication.
  • Interventional Orthobiologics and Regenerative Procedures: Regenerative therapies, including treatments like Platelet-Rich Plasma (PRP) and Bone Marrow Concentrate (BMC), support the body’s natural healing processes. Procedures using Regenexx injectates utilize a patient’s own healing agents to help promote tissue repair by targeting injured tissues directly. For persistent joint pain, interventional orthobiologic procedures offered by physicians in the licensed Regenexx network may help provide targeted treatments that may support joint health and function without the side effects associated with prolonged NSAID use.
  • Dietary and Lifestyle Modifications: Anti-inflammatory diets rich in fruits, vegetables, whole grains, lean proteins, and omega-3 fatty acids may naturally reduce chronic inflammation. Maintaining a healthy weight, staying active, and managing stress also contribute to overall health and reduced inflammation.
  • Heat and Cold Therapy: Cold therapy helps reduce swelling and numb pain, especially following an injury, while heat therapy aids in relaxing muscles, reducing stiffness, and improving blood flow, which can provide pain relief and support tissue healing.

However, some research may indicate that prolonged icing can slow healing by reducing blood flow to the injured area. Additionally, long-term rest or immobilization can weaken the muscles around the knee.

  • Mind-Body Techniques: Techniques such as meditation, mindfulness, and guided imagery can help manage chronic pain by reducing stress and enhancing relaxation, which may improve pain perception without medication.

These alternatives offer pathways for managing pain in ways that may support healing and well-being, potentially reducing the need for anti-inflammatory medications.

What Can We Learn About NSAID Dosing And Regenerative Medicine?

Timing is crucial when administering NSAIDs, particularly for patients undergoing regenerative treatments. If NSAIDs are necessary for managing pain, they are best taken in the morning to allow the natural healing processes associated with regenerative therapies to proceed with minimal interference at night. 

In the evening, non-anti-inflammatory pain relievers such as acetaminophen or, if necessary, milder alternatives like tramadol, may be preferable as they do not inhibit inflammation.

Quality sleep is also essential for healing, as rest supports the body’s repair and regeneration processes. Addressing any sleep issues before regenerative procedures, such as PRP or BMC treatments, may help enhance recovery outcomes. Good sleep may help promote optimal conditions for tissue repair, which is particularly beneficial in regenerative medicine.

This understanding underscores the importance of further research on how medication timing impacts recovery. As regenerative medicine aims to promote healing rather than simply mask pain, optimizing body functions such as sleep and carefully timing medications may help support the results of regenerative therapies.

Discover Alternatives To NSAIDs For Pain Management

Exploring alternatives to NSAIDs for pain management offers options that may help support the body’s healing processes and reduce reliance on traditional anti-inflammatory medications. 

Approaches such as physical therapy, lifestyle modifications, and regenerative medicine provide pathways to manage pain without the risks associated with prolonged NSAID use. These alternatives can benefit individuals managing chronic pain or those seeking treatments aligned with regenerative healing goals.

Considering these options for informed decisions about their pain management strategies helps to promote a healthier, more sustainable approach to managing pain and supporting overall health.

Medically Reviewed By:

Dr. Chaz Fausel, MD

Dr. Chaz Fausel is a Denver-based interventional orthopedics specialist and Regenexx educator, trained at Emory and the Centeno-Schultz Clinic.
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