Several effective options exist for arthritis pain, ranging from over-the-counter pills and topical gels to prescription medications and supplements. The best choice depends on your type of arthritis, which joints are affected, and how severe the pain is. Here’s what works, what the tradeoffs look like, and how to think about combining approaches.
Over-the-Counter Pain Relievers
For most people, the first line of defense is an anti-inflammatory painkiller like ibuprofen (Advil, Motrin) or naproxen (Aleve). These are more effective than acetaminophen (Tylenol) for arthritis because they reduce inflammation in the joint, not just the pain signal. Acetaminophen only blocks pain. If your joints are swollen, stiff, or warm to the touch, an anti-inflammatory will address more of what’s going on.
That said, acetaminophen still has a role. Taking it alongside a lower dose of an anti-inflammatory can provide solid pain relief while reducing the side effects of both. If you use acetaminophen on its own, keep your daily total under 3,000 milligrams to protect your liver.
Anti-inflammatory painkillers carry their own risks. All of them, whether older formulations or newer COX-2 selective versions, increase the chance of cardiovascular problems like heart attack and stroke. This applies even to short-term use and even in people without a history of heart disease. They can also raise blood pressure, cause fluid retention, and reduce blood flow to the kidneys. If you have heart disease, kidney problems, or a history of stomach ulcers, these drugs may not be safe for regular use.
Topical Gels and Creams
If you want to avoid swallowing pills, or if your pain is concentrated in one or two joints, topical treatments deliver medication directly where it’s needed. Diclofenac gel (sold over the counter as Voltaren Arthritis Pain) is a 1% anti-inflammatory gel you apply to up to two body areas, four times a day. Because the drug absorbs through the skin rather than circulating through your whole body, it produces far fewer stomach and cardiovascular side effects than oral anti-inflammatories.
Prescription-strength topical diclofenac is also available as a liquid solution for the knee, in both twice-daily and four-times-daily formulations. Capsaicin cream, derived from chili peppers, works differently: it depletes the chemical that nerve endings use to send pain signals. It takes consistent use over a week or two before the effect builds up, and it causes a burning sensation on the skin that fades with repeated application.
Turmeric and Other Supplements
Turmeric (specifically its active compound, curcumin) is one of the few supplements with meaningful clinical evidence behind it. A systematic review in BMJ Open Sport & Exercise Medicine found that turmeric produced large improvements in both pain and physical function compared to placebo in people with knee osteoarthritis. When compared head-to-head with anti-inflammatory drugs, turmeric performed similarly, with only small differences between the two. That’s a notable result for a supplement.
Glucosamine and chondroitin are probably the most widely marketed joint supplements, but the evidence is thinner than many people assume. The American College of Rheumatology has stated there is insufficient evidence to recommend glucosamine, chondroitin sulfate, fish oil, or vitamin D for osteoarthritis. Some people report subjective improvement, but clinical trials haven’t consistently shown meaningful benefits over placebo.
Joint Injections
When oral or topical treatments aren’t enough, injections directly into the joint are a common next step. The two main types are corticosteroid injections and hyaluronic acid (sometimes called “gel” or “lubricant” injections).
Corticosteroid injections deliver a powerful anti-inflammatory directly into the joint space and typically provide relief within a few days. The effect wears off over weeks to months, and most doctors limit how frequently you receive them because repeated steroid injections may accelerate cartilage breakdown over time. Hyaluronic acid injections aim to restore some of the natural cushioning fluid in the joint and are usually given as a series of weekly shots. Studies comparing the two approaches have found no significant difference in pain or function at three or six months. The choice often comes down to convenience (one shot versus three) and how your body responds individually.
Prescription Options for Inflammatory Arthritis
If you have rheumatoid arthritis or another inflammatory form, pain relief alone isn’t the goal. The disease itself needs to be slowed down. Disease-modifying drugs work by dialing back the immune system’s attack on your joints. Methotrexate is the most commonly prescribed first-line option and remains the backbone of treatment for rheumatoid arthritis. If it isn’t enough on its own, your rheumatologist may add a biologic, a class of injectable or infused medications that block specific immune proteins driving the inflammation. These target molecules like tumor necrosis factor (TNF) or interleukin-6, which fuel joint destruction.
A newer class of pills called JAK inhibitors works by interrupting the signaling pathways inside immune cells. These are taken orally rather than injected, which some people prefer, though they carry specific risks your doctor will discuss. The 2025 EULAR guidelines continue to recommend starting with methotrexate and escalating to biologics or JAK inhibitors based on how well you respond.
Medications That Target Pain Sensitization
Chronic arthritis can change the way your nervous system processes pain. Over time, your brain and spinal cord may amplify pain signals, making your joints hurt more than the level of inflammation alone would explain. This is called central pain sensitization, and it’s why some people still have significant pain even after inflammation is well controlled.
Certain medications originally developed for nerve pain or depression can help with this component. Pregabalin, which calms overactive nerve signaling, showed significant improvements in pain scores and hand function in a randomized trial of people with hand osteoarthritis. Duloxetine, which increases levels of two brain chemicals involved in the body’s natural pain-dampening system, has shown efficacy for knee osteoarthritis pain and also improved outcomes in hand arthritis when participants completed the full course. These aren’t painkillers in the traditional sense. They work by turning down the volume on a nervous system that has become oversensitive.
Combining Approaches
Most people with arthritis end up using more than one strategy. A practical combination might look like a topical anti-inflammatory gel on affected joints during the day, an oral anti-inflammatory on particularly bad days, and a turmeric supplement as a daily baseline. If your pain has a sensitization component (widespread tenderness, pain that seems disproportionate to swelling), adding something like pregabalin or duloxetine may address what the other treatments miss.
Physical activity, while not a medication, consistently outperforms many of these treatments in long-term studies. Strengthening the muscles around an arthritic joint reduces the load on damaged cartilage and can meaningfully decrease pain. The best outcomes typically come from pairing the right medications with regular, joint-friendly movement like walking, swimming, or cycling.