by Matthew Henderson, MPT
Masters of Physical Therapy
Updated: Nov 29th, 2022
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Medications to help relieve your knee pain comes in many types. Information and evidence on topical (skin-based) and oral medications is included in this review.
TOPICAL
NON-STEROIDAL BASED
Topical NSAIDs (non-steroidal anti-inflammatory drugs), have been shown to be effective at controlling mild to moderate knee pain. They generally have less side effects than oral NSAIDs and are easy to apply. Fairly low cost. Diclofenac is the drug-class for the majority of topical pain relief creams. COMMON BRANDS - Voltaren - Cambia - Zipsor POTENTIAL SIDE EFFECTS - Irritated skin - Itching/red skin Less common side effects exist. You should speak with a medical professional to discuss the potential side effects of any drug.
MENTHOL-BASED
This is a type of cream applied to the skin for pain relief. Menthol is the active ingredient. It provides the perception of cold to the muscles and joint, inhibiting the perception of pain. These types of pain relief creams are based on the "Gate Control Theory" of pain perception. Temperature and pain travel on the same types of nerves or "nerve tracts" when headed toward your brain. The cooling sensation theoretically inhibits the perception of pain by taking up a portion of the nerve fibers. COMMON BRANDS - Biofreeze - Cryoderm - Somba POTENTIAL SIDE EFFECTS - Skin irritation - Persistent burning sensation This medication is for use on the skin only. Apply 3-4 times daily. Rug into skin gently. Avoid getting this medication into the eyes, mouth or nose. If this happens, be sure to flush the area thoroughly with water. Do not use if pregnant or breastfeeding. Less common side effects exist. You should speak with a medical professional to discuss the potential side effects of any drug.
CAPSAICIN-BASED
Capsacin is taken from chili peppers and creates a burning sensation on the skin. In large doses, like eating a chili pepper, this burning is uncomfortable. However, in smaller doses, it can create a warming sensation that helps relieve pain. These type of creams theoretically work by reducing a pain neurotransmitter in your brain, Substance P. COMMON BRANDS - Capzasin HP - Capsin - Icy Hot POTENTIAL SIDE EFFECTS - Burning, itching skin - Swelling or soreness around applied area This medication is for use on the skin only. Apply 3-4 times daily. Rug into skin gently. Avoid getting this medication into the eyes, mouth or nose. If this happens, be sure to flush the area thoroughly with water. Do not use if pregnant or breastfeeding. Less common side effects exist. You should speak with a medical professional to discuss the potential side effects of any drug.
ORAL DRUGS
NON-STEROIDAL BASED
We will focus on NSAIDs, or "non-steroidal anti-inflammatory drugs" for this review. Steroids are also used for inflammation, but always require a physician's prescription. NSAIDs stands for "non-steroidal anti-inflammatory drugs." These drugs are available over-the-counter in lower doses. NSAIDs reduce inflammation and can help manage pain as well. If you require a higher dose it will require a physicians approval. COMMON ORAL BRANDS - Ibuprofen (Motrin, Advil etc.) - Aspirin (the first NSAID) - Naproxen (Aleve) - Dexamethasone POTENTIAL SIDE EFFECTS - Heartburn - Stomach pain/ulcers - Bleeding - Headaches - Nausea/vomiting - Higher risk of heart attack or stroke These risks may be even higher in people who have diabetes or high cholesterol, smoke, or have a history of previous heart attacks/strokes. Once again, this information is general in nature. You should speak with a medical professional to discuss the potential side effects of any drug.
ACETAMINOPHEN
Acetominophen addresses pain and fever, and is found in thousands of products. Addresses mild to moderate pain. Has no anti-inflammatory effect. COMMON BRANDS - Tylenol - FeverAll - Excedrin (often contains NSAIDS as well) POTENTIAL SIDE EFFECTS - Swelling - Rash - Itching/hives - Difficulty swallowing - Difficulty breathing This information is general in nature. You should speak with a medical professional to discuss the potential side effects of any drug.
THE EVIDENCE
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EVIDENCE RATING: GOOD/STRONG
Extensive research has been done on the use of a variety of medications to treat knee pain. We have reviewed each class separately to minimize confusion. NSAIDs (ORAL & TOPICAL) - STRONG EVIDENCE An excellent review of existing studies on the use of oral and topical NSAIDs was completed in 2021 by Costa et al (1). They concluded oral NSAIDs were effective for pain and function. However, they cautioned against long-term use of these drugs due to an increase in the risk of adverse events. They determined topical diclofenac (Voltarin, Pennsaid) should be considered as the first line medication treatment for knee osteoarthritis. This was due to its high efficacy and generally lower side effects and reduced systemic exposure. UPDATE NOV 27th 2022: A new study out of the University of California, San Francisco, revealed that long term use of NSAIDs may potentially lead to increased joint inflammation. No signficant effect was noted on cartilate thickness. They determined this through MRI's on over 1,000 subjects. This study is not conclusive but indicates increased caution when taking NSAIDs for long periods of time. We once again, highly recommend consulting with a physician. ACETAMINOPHEN - STRONG EVIDENCE A meta-analysis reviewing the effects of acetaminophen on reducing the pain of osteoarthritis found it is an effective medication for pain relief. However, although safer than NSAIDs, it was also less effective (3). They recommended acetaminophen as the first line of oral drugs treatment, with NSAIDs reserved for those who don't respond. MENTHOL CREAM - GOOD EVIDENCE A 2017 review of clinical studies on "topical menthol" or "biofreeze" found both a statistical and clincially significant pain reduction in studies of the hand, neck, and back. Results were mixed for muscle soreness. Individuals with knee pain had statistically significant reduction in knee pain, but did not meet the criteria for clinical significance (4). NOTE: This study was sponsored by Performance Health Research, the manufacturer of Biofreeze. CAPSAICIN CREAMS - GOOD EVIDENCE A study comparing the efficacy of topical NSAIDs with topical capsaicin for pain relief in osteoarthritis concluded they were both effective at licensed doses (5). Another study by Chrubasik et al (6), comparied capsaicin topical treatment to a placebo group, after 3-weeks of treatment the median pain score had decreased by 49% (capsaicin group) and 23% (placebo group.) There were more adverse events in the capsaicin group, but it was generally well tolerated. The results indicated that capsaicin cream is potentially useful to patients with chronic soft tissue pain.
REFERENCED STUDIES
1. Costa et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis. BMJ 2021;375:n2321. https://doi.org/10.1136/bmj.n2321 2. https://www.prnewswire.com/news-releases/nsaids-may-worsen-arthritis-inflammation-301681834.html 3. W Zhang, A Jones, and M Doherty. Does paracetamol (acetaminophen) reduce the pain of osteoarthritis?: a meta-analysis of randomised controlled trials. Ann Rheum Dis. 2004 Aug; 63(8): 901–907. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1755098/ 4. Page et al. The Clinical Effectiveness of Biofreeze Topical Analgesic on Musculoskeletal Pain: A Systematic Review. Journal of Performance Health Research. Vol 1, Issue 1. Pages 1-10. 5. Persson et al. The relative efficacy of topical non-steroidal anti-inflammatory drugs and capsaicin in osteoarthritis: a network meta-analysis of randomised controlled trials. Osteoarthritis Cartilage. 2018 Dec; 26(12): 1575–1582. doi: 10.1016/j.joca.2018.08.008 6. Chrubasik et al. Effectiveness and safety of topical capsaicin cream in the treatment of chronic soft tissue pain. First published: 22 November 2010. https://doi.org/10.1002/ptr.3335
These medications and creams can potentially help reduce your knee pain. The evidence recommends acetaminophen as the first line of oral medications, with NSAIDs reserved for those who don't respond. Topically, NSAID skin creams were found to be both highly effective and lower risk than oral NSAIDs. This is our interpretation of the evidence, but opinions will vary.
It's important to remember medications are complicated and contraindications abound. Always consult a physician before trying a new medication.
CONCLUSIONS
PAIN RELIEF
The Topical Brands We Trust
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​FDA-approved to treat osteoarthritis and generalized inflammation in the knee. One of the best over-the-counter painkilling creams on the market. Active ingredient is Diclofenac. Minimal common side effects.
This is a good treatment, with solid evidence, and at a reasonable price point.
Before taking any medications, consult a physician for a thorough evaluation.
The original menthol-based pain relieving gel. Invented in 1991 by Dr. Danne Mantague-King who set out to develop a pain relief solution for his grandmother who had arthritis. Used for many years by physical therapists and trainers with professional and college athletes.
The #1 clinically recommended topical pain reliever in its class.
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NOTE: This product is excellent, but must be used correctly. Be very careful when applying this product. If you apply it to an area and then touch that area later, it could transfer back to your hands. If you then touch your face or eyes it could be quite painful. Be cautious of coming in contact with children to avoid transfer to them as well.
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Before taking any medications, consult a physician for a thorough evaluation.
High-quality manufacturer. Similar to BioFreeze, except the capsaicin provides a perception of heat instead of cold. Choosing between the two products is based solely on your personal preference.
NOTE: This product is excellent, but must be used correctly. Be very careful when applying this product. If you apply it to an area and then touch that area later, it could transfer back to your hands. If you then touch your face or eyes it could be quite painful. Be cautious of coming in contact with children to avoid transfer to them as well.
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Before taking any medications, consult a physician for a thorough evaluation.