Several different types of medications, both over-the-counter and prescription drugs, can be used to manage knee pain. They can be administered orally by taking a pill, topically by applying the medication to the skin, or intra-articularly by being injected directly into the knee joint.

NSAIDs

Over-the-Counter Medications

Over-the-counter pain-relieving medications such as acetaminophen (Tylenol) and ibuprofen (Advil), or anti-inflammatory medication like naproxen sodium (Aleve), can help reduce knee pain, swelling, and inflammation in the knee joint.

Prescription Medications

If symptoms are severe enough, your healthcare provider may prescribe a higher dosage of a nonsteroidal anti-inflammatory drug (NSAID) to help decrease your knee pain so you can sit, stand, and walk with less discomfort. 

Topical Treatments

Over-The-Counter Medicine

Over-the-counter creams and ointments, especially those that contain capsaicin, an extract derived from chili peppers, can be applied topically to the knee to help relieve pain by decreasing the intensity of pain signals sent along nerve pathways.

Prescription Creams

Prescription creams, in either gel or liquid form, that contain diclofenac can be applied topically to the knee to provide pain relief. There are varying formulations that contain either 1%, 1.5%, or 2% diclofenac depending on the strength of medication needed, which will be determined by your prescribing healthcare provider.

Topical treatment can help provide pain relief for people who cannot or do not want to take oral pain medications. Topical treatments are especially helpful for people who take other medications since oral pain relievers can interact with other drugs. Oral pain relievers can also cause stomach ulcers and bleeding, making topical pain-relieving medications more suitable for people with gastrointestinal issues.

Pain Patches

Lidocaine patches may be prescribed by your healthcare provider to help alleviate your knee pain. Lidocaine is a local anesthetic that helps to relieve pain by blocking nerves from transmitting pain signals. The medication is delivered transdermally through the skin, which absorbs the medication on the adhesive side of the patch.

A lidocaine patch can be applied directly to the skin once a day for up to 12 hours. You can apply the patch over the area where you are having the most pain, but should avoid placing it directly on top of the knee joint. The patch should not be applied if there are any cuts or breaks in the skin. 

Prescription Pain Medications

Corticosteroids

Corticosteroids such as cortisone and prednisone may be prescribed to reduce pain, swelling, and inflammation in the body to lessen knee pain. Corticosteroids should be used with caution since prolonged corticosteroid usage can cause weakening of the muscles, tendons, and ligaments surrounding the knee, and increases the risk of developing certain conditions like osteoporosis and Cushing’s syndrome. 

Opioid Pain Relievers

Opioid medications like oxycodone, hydrocodone, morphine, and tramadol may be prescribed by your healthcare provider to help relieve knee pain if over-the-counter or prescription NSAIDs are not effective.

Injections

Corticosteroids

Corticosteroids, or cortisone injections, are anti-inflammatory medications that can be injected into the knee joint directly to reduce pain, swelling, and inflammation. They are the most commonly used type of knee injections for treating knee pain from osteoarthritis.

According to the American College of Rheumatology and Arthritis Foundation guidelines for managing knee osteoarthritis, corticosteroid injections are recommended over any other type of injection due to improved outcomes and effectiveness in alleviating symptoms.

Corticosteroid injections are performed under local anesthesia, where you will be awake for the procedure but your knee will be numbed. A small amount of anesthesia will be injected into your knee before the corticosteroid, which usually begins to work two to three days later.

Corticosteroid injections can help relieve pain and reduce symptoms between six weeks and six months after the procedure, although the injections are not effective for everyone. You will typically not be allowed to receive more than two or three injections per year.

Hyaluronic Acid

Viscosupplementation, sometimes called gel injections, involves injecting hyaluronic acid into the knee to decrease pain and improve joint movement. Hyaluronic acid used for injections is derived from the combs of chickens.

Hyaluronic acid is a gel-like substance that occurs naturally in the synovial fluid within each joint capsule that surrounds all joints. Hyaluronic acid serves as a lubricant that allows bones to move smoothly within a joint and provides shock absorption to decrease pressure and friction within joints. Over time, hyaluronic acid levels in the joints decrease, especially as the joints wear down with osteoarthritis.

You may receive between one and five injections if you choose to undergo this treatment. If there is excess swelling and fluid buildup in the knee joint, your healthcare provider will use a needle to aspirate, or remove, the fluid before injecting the hyaluronic acid. You should avoid prolonged standing, walking, jogging, running, or heavy lifting for the first 48 hours after receiving a hyaluronic acid injection.

It may take up to four weeks to notice any significant improvement, and the lasting effects can vary from two to six months. Hyaluronic acid injections may be repeated about once every six months.

There is no evidence, however, that suggests that hyaluronic acid injections provide significant relief for knee pain, and they are not recommended for managing knee osteoarthritis under the American College of Rheumatology and Arthritis Foundation guidelines.

Local Anesthetics

A local anesthetic, most commonly lidocaine, can be injected into the knee. Lidocaine has numbing and anti-inflammatory effects that can reduce the intensity of pain signals. Recent research suggests that effects can last for three months or more.

Lidocaine is also often injected into the knee before a corticosteroid injection in order to numb the area and make the injection less uncomfortable. The lidocaine may produce immediate, short-term pain relief in the knee, but often wears off a few hours after the injection since less lidocaine is used to prepare for a corticosteroid injection than the amount used for a standalone lidocaine injection.

Botox

Botulinum toxin, commonly known as Botox, is a naturally occurring toxin produced by bacteria that are commonly used to relax forehead wrinkles and decrease muscle spasticity in neurologic conditions by paralyzing nerves.

Preliminary research suggests that Botox injections can be used to treat knee osteoarthritis by paralyzing the nerves that send chronic pain signals to the brain. It may take up to four weeks for the full effect to set in, and pain relief may last up to six months.

Platelet-Rich Plasma 

Platelet-rich plasma injections are made up of your own blood plasma that contains a high concentration of platelets, also called thrombocytes, which are small blood cells that are involved in blood clotting. Platelets release substances called growth factors that stimulate healing after an injury. When injected into the knee, platelet-rich plasma has the potential to help damaged cartilage heal, but this has not yet been proven.

Your healthcare provider will use a syringe to draw a small amount of blood from a vein in your arm and use a centrifuge to separate the plasma and platelets. Blood centrifugation takes about 15 minutes to separate the blood components. Your healthcare provider will then inject the platelet-containing plasma directly into your knee joint. Ultrasound may be used to help guide accuracy of the injection.

DMARDs

Disease-modifying antirheumatic drugs (DMARDs) are specifically prescribed for rheumatoid arthritis and other rheumatic and autoimmune conditions. DMARDs decrease inflammation throughout the body by altering the immune system response.

Because DMARDs decrease your immune system response, you may be at an increased risk of infection while taking these medications. Make sure to talk with your healthcare provider about the risks and benefits of taking DMARD medication.