For knee pain, the most effective starting point is a topical anti-inflammatory gel applied directly to the joint. Clinical guidelines from the American College of Rheumatology strongly recommend trying a topical NSAID before reaching for oral painkillers, because these gels work just as well for knee pain while exposing the rest of your body to far less medication. Beyond topicals, your options range from over-the-counter pills to injections to supplements, each with different tradeoffs worth understanding.
Topical Anti-Inflammatory Gels
Topical NSAIDs, like diclofenac gel (sold as Voltaren in the U.S.), are the current first-line recommendation for knee osteoarthritis. A network meta-analysis published in Osteoarthritis and Cartilage found that topical NSAIDs were superior to acetaminophen for improving knee function, and statistically no different from oral NSAIDs. In other words, rubbing a gel on your knee works about as well as swallowing a pill, with a fraction of the systemic side effects.
The standard approach is applying the gel four times a day. Because most of the medication stays local to the joint, you avoid the stomach and kidney issues that come with long-term oral NSAID use. The main downside is that topicals work best on joints close to the skin surface, and the knee happens to be ideal for this.
Capsaicin Cream
Capsaicin, the compound that makes chili peppers hot, is another topical option conditionally recommended by the ACR. It works by depleting a chemical called substance P from nerve fibers near the joint, which disrupts pain signaling. The catch is that you need to apply it four times daily, and it takes consistent use over one to two weeks before you notice meaningful relief. There’s also a burning sensation during the first few applications that fades as the nerves desensitize. One study found that 0.075% capsaicin cream applied four times daily significantly improved both pain and tenderness in knee osteoarthritis.
Over-the-Counter Oral Pain Relievers
If topicals aren’t enough on their own, oral NSAIDs like ibuprofen and naproxen are the next step. Guidelines recommend using the lowest effective dose for the shortest time possible. Both reduce inflammation directly at the joint, which makes them more effective than acetaminophen (Tylenol) for most types of knee pain. Acetaminophen can take the edge off mild discomfort, but it doesn’t address inflammation, and the research consistently shows it performs worse than NSAIDs for knee osteoarthritis.
The tradeoff with oral NSAIDs is side effects over time. Long-term daily use increases the risk of ulcer bleeding by two to four times, depending on the specific drug and dose. Naproxen has a unique profile: it blocks clotting in platelets enough to offset extra heart attack risk, but that same property makes stomach bleeding more likely. Ibuprofen carries slightly less bleeding risk but doesn’t offer that cardiovascular protection. For occasional flare-ups, these risks are small. For daily use over months or years, they add up and are worth discussing with your doctor.
Prescription Options
When over-the-counter options fall short, a few prescription routes can help. One that surprises many people is duloxetine, originally developed as an antidepressant. It works by increasing the activity of serotonin and norepinephrine in the brain, which turns down the volume on chronic pain signals from the nervous system. The typical dose for musculoskeletal pain is 60 mg once daily, sometimes starting at 30 mg for the first week. The ACR conditionally recommends it for knee osteoarthritis, and it can be especially useful when pain has become persistent and centralized, meaning your nervous system has become more sensitive to pain signals over time.
Tramadol is another conditionally recommended option, though it sits in the opioid family and carries dependency risks. The ACR specifically recommends against stronger opioids for knee osteoarthritis, given the poor long-term risk-benefit balance.
Injections for More Targeted Relief
Corticosteroid injections deliver a powerful anti-inflammatory directly into the knee joint. Relief typically lasts weeks to a few months, and they tend to work fastest, often within days. They’re strongly recommended by the ACR for flare-ups, but repeated injections over time may contribute to cartilage thinning, so most providers limit how often they’re given.
Hyaluronic acid injections take a different approach, essentially supplementing the natural lubricant in your joint. The effect builds gradually over several weeks and is often described as the knee “moving more smoothly.” Pain relief can last several months. These are more commonly used for mild to moderate osteoarthritis where the joint still has reasonable cartilage remaining.
Platelet-Rich Plasma (PRP)
PRP injections use a concentrated preparation of your own blood platelets, which contain growth factors that may promote tissue repair. The evidence is promising but still evolving. A 2021 meta-analysis of randomized controlled trials found PRP outperformed both saline injections and hyaluronic acid in most studies, with benefits lasting 6 to 12 months. Compared to steroid injections, steroids often provide better relief in the first four to six weeks, but PRP tends to outperform steroids at the three to six month mark. Mayo Clinic has treated more than 1,100 patients with PRP without any serious adverse events. The main barrier is cost, as PRP is rarely covered by insurance.
Supplements: Glucosamine, Chondroitin, and Turmeric
Glucosamine and chondroitin are among the most popular joint supplements, but the evidence is genuinely mixed. A 2018 combined analysis of 29 studies with over 6,000 participants found that glucosamine or chondroitin taken separately did reduce pain, but taking them together showed no significant benefit over placebo. Individual study results were inconsistent, and expert bodies have reached conflicting conclusions. The ACR and the Osteoarthritis Research Society International both strongly recommend against glucosamine and chondroitin for knee osteoarthritis, citing lack of reliable efficacy. The American Academy of Orthopaedic Surgeons, on the other hand, includes glucosamine among supplements that may help mild to moderate knee pain, while cautioning that the evidence is inconsistent. If you want to try them, a three-month trial is reasonable to see if you notice a difference, but don’t expect dramatic results.
Turmeric (specifically its active compound curcumin) has more encouraging recent data. In one clinical trial, 500 mg of curcumin taken three times daily was compared to a standard dose of the prescription NSAID diclofenac. After one month, 94% of the curcumin group and 97% of the diclofenac group reported at least 50% improvement in their arthritis symptoms. That’s a surprisingly close result for a supplement. The caveat is that curcumin is poorly absorbed on its own, so formulations designed to improve absorption (often labeled as containing piperine or using specialized delivery systems) are important. Standard turmeric powder from your spice rack won’t deliver therapeutic doses.
Choosing the Right Approach
The best strategy for most people combines more than one option. A topical NSAID for daily management, an oral NSAID for flare-ups, and physical activity to strengthen the muscles around the knee is a solid foundation. If pain persists despite these measures, injections or prescription medications become reasonable additions. The key principle in current guidelines is starting with the safest effective option and escalating only as needed, which is why topical treatments come before oral ones, and oral NSAIDs come before opioids.
What works also depends on the cause of your pain. Osteoarthritis, runner’s knee, ligament injuries, and post-surgical pain all respond differently. Osteoarthritis benefits most from anti-inflammatories and injections. Overuse injuries like runner’s knee often respond well to rest, ice, and targeted exercises. If your knee pain started suddenly after an injury, or if you have significant swelling, locking, or instability, those are signs that something structural may need attention beyond pain management alone.