Medications for Osteoarthritis and Musculoskeletal Pain

The goal of OA treatment is to relieve pain and improve function without causing harm to the patient. A 2021 meta-analysis analyzed the efficacy and safety of oral and topical NSAIDs and acetaminophen for knee OA. The study authors found that topical NSAIDs produced improvement in function over acetaminophen but not over oral NSAIDs in the treatment of OA of the knee. The safety profile for topical NSAIDs was superior to both acetaminophen and oral NSAIDs (Table 3).9

Table 3. Risk for Adverse Cardiovascular and Gastrointestinal Outcomes9

OutcomeTopical NSAIDs vs Acetaminophen (reference)Topical NSAIDs vs Oral NSAIDs (reference)
Major CVD0.730.74
Venous thromboembolism0.810.73
GI bleeding0.530.71
CVD, cardiovascular disease; GI, gastrointestinal; NSAID, nonsteroidal anti-inflammatory drug
Adapted from Zeng et al.9

In another meta-analysis comparing NSAIDs to opioids, researchers concluded that topical diclofenac 70 to 81 mg per day should be the first-line treatment for knee OA because of the improved safety and efficacy profile over oral NSAIDs and opioids. The benefits do not outweigh the risks for the use of opioids in the treatment of OA.10

Topical Diclofenac

Diclofenac is the only topical NSAID currently available in the United States and is supplied in a 1.3% patch, 1% gel, and 1.5% and 2% solution.11-13 The patch and solution are available by prescription and the gel can be purchased over the counter or by prescription. Recommended adult dosing with the gel is 2 grams applied to a 2.25-inch area up to 4 times daily for joints in the hands, elbows, or wrists. For the knee, ankle, or foot joints, 4 grams should be applied to a 4.5-inch area up to 4 times daily.11 The maximum dose per area is 16 grams per day for the lower extremities, 8 grams per day for the upper extremities, and 32 grams maximum daily for total body dose.11 The diclofenac patch can be applied once or twice daily to the affected area.12 The 1.5% solution is for 40 drops to each affected knee up to 4 times daily. The drops should be applied 10 at a time and rubbed in evenly before applying the next 10 drops.13 The 2% solution is administered via pump.14 Two pump actuations (40 mg) are applied to each affected knee up to twice daily.14

Continue Reading

As with all NSAIDs, the labeling for topical diclofenac contains a black box warning that NSAIDs may cause an increased risk of serious and potentially fatal cardiovascular adverse events and should not be used in the setting of coronary artery bypass graft surgery.11-14 The lowest possible dose of topical diclofenac should be used in patients with known or risk factors for cardiovascular disease.

Other topical NSAID formulations (eg, ibuprofen, ketoprofen) have shown efficacy in clinical trials but are not available in the United States. All topical agents should be rubbed in thoroughly and applied to clean dry skin. They should not be applied to any open or irritated areas. Hands should be washed thoroughly after application. All have the potential to cause skin irritation.


Topical NSAIDs provide effective pain relief with minimal safety concerns for mild to moderate musculoskeletal pain and are recommended by the ACP, AAFP, and ACR as first-line therapy. The evidence strongly supports the efficacy and safety of topical NSAIDs for use in acute and chronic musculoskeletal conditions. Head-to-head clinical trials of different topical NSAIDs, however, are lacking. Data regarding the contrasts between formulations, concentrations, and use for varying conditions would further define the possible benefits of topical NSAIDs. Further research is needed in these areas.

Lynda Jarrell, DNP, APRN, FNP-BC, is clinical assistant professor and director of the Family Nurse Practitioner program at the University of Texas Arlington; Ka’Shiris W. Perryman, DNP, APRN, FNP-BC, CNE, LNC, is clinical assistant professor in the Family Nurse Practitioner and Doctor of Nursing Practice programs at the University of Texas Arlington.


1. McMahon SB, Dargan P, Lanas A, Wiffen P. The burden of musculoskeletal pain and the role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in its treatment. Ten underpinning statements from a global pain faculty. Curr Med Res Opin. 2021;37(2):287-292. doi:10.1080/03007995.2020.1847718.

2. Centers for Disease Control and Prevention. National Center for Chronic Disease Prevention and Health Promotion. Arthritis. Updated November 3, 2021. Accessed April 8, 2022.

3. Qaseem A, McLean RM, O’Gurek D, et al. Nonpharmacologic and pharmacologic management of acute pain from non-low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians. Ann Intern Med. 2020;173(9):739-748. doi:10.7326/M19-3602

4. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020;72(2):149-162. doi:10.1002/acr.24131

5. Hawthorn C. A narrative review: the use of the topical NSAID ibuprofen for the treatment of knee osteoarthritis. supporting clinician decision-making in the first-line treatment of osteoarthritis. Rehabil Process Outcome. 2020;9:1179572720914945. doi:10.1177/1179572720914945

6. Geller DE, Swan BA. Recent evidence of nurse practitioner outcomes in a variety of care settings. J Am Assoc Nurse Pract. 2020 Jul 7. doi:10.1097/JXX.0000000000000451

7. Moayedi M, Davis KD. Theories of pain: from specificity to gate control. J Neurophysiol. 2013;109(1):5-12. doi:10.1152/jn.00457.2012

8. van Rensburg R, Reuter H. An overview of analgesics: NSAIDs, paracetamol, and topical analgesics . S Afr Fam Pract. 2019;61(1):S4-S10. doi:10.4102/safp.v61i1.5045

9. Zeng C, Doherty M, Persson MSM, et al. Comparative efficacy and safety of acetaminophen, topical and oral non-steroidal anti-inflammatory drugs for knee osteoarthritis: evidence from a network meta-analysis of randomized controlled trials and real-world data. Osteoarthritis Cartilage. 2021;29(9):1242-1251. doi:10.1016/j.joca.2021.06.004

10. da Costa BR, Pereira TV, Saadat P, 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. doi:10.1136/bmj.n2321

11. Voltaren gel. Prescribing information. Endo Pharmaceuticals; 2016. Accessed April 18, 2022.

12. Flector patch. Prescribing information. Pfizer; 2018. Accessed April 18, 2022.

13. Pennsaid topical solution. Prescribing information. Mallinckrodt Brand Pharmaceuticals; 2009. Accessed April 18, 2022.

14. Pennsaid topical solution. Prescribing information. Mallinckrodt Brand Pharmaceuticals; 2014.