Types of Knee Injections For Pain From Osteoarthritis

Osteoarthritis of the knee is a degenerative joint disease. It causes pain, swelling, and stiffness of the joint. The cartilage in the knee typically acts like a shock absorber, protecting the knee joint. In osteoarthritis, the cartilage breaks down, causing pain and other symptoms. This ongoing, nagging knee pain can make everyday activities difficult.

Knee injections for pain from osteoarthritis (OA) are a non-surgical treatment doctors may recommend for relieving pain. The effects of the injections vary depending on the substance injected into the knee joint and may last from six months to 15 years.

Each type of injection for knee pain works differently, but the main goal is to treat osteoarthritis of the knee. Several types of knee injections can reduce inflammation and relieve knee joint pain. Before making a decision on how to move forward, you should speak with your doctor about treatment options. Knee injections for pain are a medical treatment, and as such, have both advantages and disadvantages that vary from person to person.

Knee Injections For Pain

Below is a list of the 10 most common types of injections for knee pain — jump to the comparison table:

  • Overview: Steroids are powerful anti-inflammatory medications that can help reduce swelling. Also known as cortisone or corticosteroid injections. They are the most common type of injection to treat knee pain from osteoarthritis. The first injection may address your pain; however, the effect is temporary and will diminish with each shot.
  • What the studies say: Research published in 20171 concluded that steroid injections in the knee were ineffective for knee arthritis. The research showed steroid injections are not as effective as once believed and can also damage cartilage.
  • Side effects: According to the research2, joint replacement patients who received steroid injections prior to joint replacement were more likely to have complications. One study3 reports patients were twice as likely to have complications after surgery. They were also three times more likely to get an infection. Another study4 reports numbing agents used for steroid injections (bupivacaine and lidocaine) could damage knee cartilage. Finally, many studies show that these medications can damage blood sugar control, cause osteoporosis to worsen, and are associated with an increased risk for a serious bone disease called avascular necrosis.
  • Overview: Hyaluronic acid (HA) injections are also known as rooster comb or knee gel injections. HA injections thicken the joint fluid in an arthritic knee to provide more cushion for the joint.
  • What the studies say: Although these injections appeared promising in the past, more recent research indicates mixed results. A 2022 study found that HA injections relieved knee pain associated with osteoarthritis for about six months. The study also found that HA injections worked better when combined with PRP.5 In a different 2022 study, the risk of severe adverse reactions was higher than with placebo, and the benefit likely did not outweigh the risk.6
  • Side effects: After the procedure, soreness and bruising at the injection site. Some patients may have difficulty moving, muscle pain or stiffness, or pain in the joint. Fewer people report severe swelling or redness in the joint likely due to an allergic reaction to the medication.
  • Overview: PRP injections are made from concentrated platelets. The patient’s blood is drawn and run through a centrifuge to concentrate the platelets and then the PRP product is injected into the knee joint. Platelets release growth factors that may reduce swelling and stimulate repair within the joint.
  • What the studies say: Several dozen studies show PRP helps relieve pain and improve function. Research has shown PRP to be more effective than gel shot (Hyaluronic Acid Injections)7. It may also promote joint healing and lower inflammation. It lasts about a year or more in mild arthritis but has shorter term results in more severe arthritis cases.
  • Side effects: Potential for pain, bleeding, or tenderness at the injection site, like any injection. Less risk for side effects because PRP uses the patient’s own blood.
  • Overview: An injection of a chemical irritant like hypertonic dextrose is used to kickstart a healing cycle. Dextrose can boost the repair of damaged ligaments in the knee joint.
  • What the studies say: Research shows that prolotherapy works better than anesthetic or steroid, but not better than PRP.8
  • Side effects: Typical site injection complications such as pain, swelling, and bruising.
  • Overview: BMC (bone marrow concentrate aka BMAC) injections contain the patient’s own mesenchymal stem cells9. These injections are usually reserved for more severe knee arthritis. The doctor takes a bone marrow sample from a patient’s back hip area and then concentrates the stem cell containing fractions in a centrifuge.
  • What the studies say: A 2018 large randomized controlled trial10, following the Regenexx procedure protocol, reported improvements in knee pain and function. Since then, two more large RCTs also showed positive results lasting up to 15 years with patients often reporting better outcomes from the BMC treated knee than their knee replacement joint. To read more on why the research shows that BMC is a stem cell therapy, please read this blog.
  • Side effects: Typical site injection complications can be common and include pain, swelling, and bruising.
  • Overview: Amniotic membrane and umbilical cord tissues are often mislabeled as “stem cell therapies”, however these tissues do not contain viable mesenchymal stem cells processing for sale to doctor’s offices. Although they contain growth factors, these levels are often lower than those of PRP.
  • What the studies say: There isn’t much research at this point showing that these treatments help knee arthritis.
  • Side effects: The cells used in these treatments are not matched 11 to the patient. Hence, they put patients at risk of Graft vs. Host disease (GVHD). Early symptoms include skin rash and mouth sores.
  • Overview: Cytokines are chemicals in the blood that may help reduce cartilage breakdown. Cytokine-rich plasma is another orthobiologic treatment. These include treatments like A2M (Alpha-2-Macroglobulin) and IRAP (Interleukin Receptor Antagonist Therapy).
  • What the studies say: Studies are still underway, but IRAP has had disappointing results12. A2M shows promise in animal studies.
  • Side effects: After the procedure soreness and bruising at the injection site. Some patients may have mild to moderate pain or stiffness are possible. Fewer people report swelling or redness in the joint.
  • Overview: Exosomes are like words and instructions used by cells between themselves. The concept is that certain exosomes may be able to provide repair messages, but we don’t yet have the ability to isolate those kinds of messages.
  • What the studies say: No clinical data shows that this works in patients with knee arthritis. Animal studies do not show information about current products being used on patients.
  • Side effects: This procedure and its potential side effects aren’t well known.
  • Overview: Ozone therapy uses oxygen molecules with an extra oxygen atom (O3). The idea is that it provides better oxygenation to the area.
  • What the studies say: 2017 research shows13 good results in treating knee osteoarthritis in trials. Research on cartilage treatment is limited.
  • Side effects: After the procedure swelling or bruising at the injection site.
  • Note: Ozone injections are currently not approved for use in the U.S.

Which Doctor Should I See For Knee Pain Injections?

Many healthcare professionals may offer knee injections. Yet, not everyone has the expertise and equipment necessary to perform the procedures. Look for a board-certified physician with expertise in musculoskeletal and image-guided knee injections — like a Regenexx physician.

Avoid blind injections or injections performed without any kind of image guidance. Trained physicians can miss the target location 20-40% of the time without image guidance. A qualified provider should have access to both ultrasound and fluoroscopy. Ultrasound and fluoroscopy are both important tools to ensure that the injection you’re receiving is being delivered into the knee joint and not into the surrounding soft tissue.

Injection type Lasts Covered by insurance Out-of-pocket cost per injection Known side effects
Injection type: Steroids Lasts: Up to 6 months Covered by insurance: Yes Out-of-pocket cost per injection: $25 to $300 Known side effects: Pain and bruising at the injection site after the procedure. Cartilage damage, increased infection rates, poor surgical outcomes, and negative systemic effects.
Injection type: Hyaluronic acid Lasts: Up to 6 months Covered by insurance: Yes Out-of-pocket cost per injection: $450 to $1,700 Known side effects: Pain and bruising at the injection site after the procedure. Some patients experience stiffness and swelling.
Injection type: Platelet-rich plasma (PRP) Lasts: 1-2 years, more severe arthritis with shorter term results. Covered by insurance: No Out-of-pocket cost per injection: $1,000 to $2,000 Known side effects: Pain and tenderness at the injection site after the procedure.
Injection type: Prolotherapy Lasts: Up to 1 year Covered by insurance: No Out-of-pocket cost per injection: $150 to $600 Known side effects: Pain and swelling at the injection site after the procedure. More research is needed.
Injection type: Bone Marrow Concentrate (BMC or BMAC containing your own stem cells) Lasts: Up to 15 years Covered by insurance: No Out-of-pocket cost per injection: $3,000 to $6,000 Known side effects: Pain and bruising at the injection site after the procedure.
Injection type: Amniotic or umbilical cord tissue Lasts: Unknown Covered by insurance: No Out-of-pocket cost per injection: $1,500 to $2,500 Known side effects: The body may reject the treatment.
Injection type: Cytokine-rich plasma Lasts: Unknown Covered by insurance: No Out-of-pocket cost per injection: $1,000 to $3,000 Known side effects: Soreness and bruising at the injection site after the procedure. Some patients experience stiffness.
Injection type: Exosome Lasts: Unknown Covered by insurance: No Out-of-pocket cost per injection: $3,500 to $6,500 Known side effects: Increased joint pain and swelling at the injection site after the procedure. Side effects are not well known.
Injection type: Microfragmented fat Lasts: Up to 2 years Covered by insurance: No Out-of-pocket cost per injection: $3,500 to $4,000 Known side effects: Pain and swelling at the injection site after the procedure. Harvest site infection.
Injection type: Ozone Lasts: Unknown Covered by insurance: Not approved in the U.S. Out-of-pocket cost per injection: Not approved in the U.S. Known side effects: Swelling and bruising at the injection site after the procedure.


1. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis. JAMA. 2017;317(19):1967. doi:10.1001/jama.2017.5283

2. MD L. Knee Injection: Background, Indications, Contraindications. Medscape.com. Published May 12, 2022. Accessed September 1, 2022.

3. Castano-Betancourt MC, Fruschein Annichino R, de Azevedo e Souza Munhoz M, Gomes Machado E, Lipay MV, Marchi E. Identification of high-risk groups for complication after arthroplasty: predictive value of patient’s related risk factors. Journal of Orthopaedic Surgery and Research. 2018;13(1). doi:10.1186/s13018-018-1036-2

4. Chu CR, Coyle CH, Chu CT, et al. In Vivo Effects of Single Intra-Articular Injection of 0.5% Bupivacaine on Articular Cartilage. The Journal of Bone and Joint Surgery-American Volume. 2010;92(3):599-608. doi:10.2106/jbjs.i.00425

5. Chavda S, Rabbani SA, Wadhwa T. Role and Effectiveness of Intra-articular Injection of Hyaluronic Acid in the Treatment of Knee Osteoarthritis: A Systematic Review. Cureus. 2022;14(4):e24503. Published 2022 Apr 26. doi:10.7759/cureus.24503

6. Pereira TV, Jüni P, Saadat P, et al. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ. 2022;378:e069722. Published 2022 Jul 6. doi:10.1136/bmj-2022-069722

7. Xing D, Wang B, Zhang W, et al. Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. International Journal of Rheumatic Diseases. 2017;20(11):1612-1630. doi:10.1111/1756-185x.13233

8. Arias-Vázquez PI, Tovilla-Zárate CA, Legorreta-Ramírez BG, et al. Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials. Advances in Rheumatology. 2019;59(1). doi:10.1186/s42358-019-0083-7

9. Lopa S, Colombini A, Moretti M, de Girolamo L. Injective mesenchymal stem cell-based treatments for knee osteoarthritis: from mechanisms of action to current clinical evidences. Knee Surgery, Sports Traumatology, Arthroscopy. 2018;27(6):2003-2020. doi:10.1007/s00167-018-5118-9

10. Centeno C, Sheinkop M, Dodson E, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. Journal of Translational Medicine. 2018;16(1). doi:10.1186/s12967-018-1736-8

11. Ashok. Crossmatching: Overview, Clinical Indications/Applications, Test Performance. Medscape.com. Published May 11, 2021. Accessed September 1, 2022.

12. Baltzer AWA, Moser C, Jansen SA, Krauspe R. Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis and Cartilage. 2009;17(2):152-160. doi:10.1016/j.joca.2008.06.014

13. Lopes de Jesus CC, dos Santos FC, de Jesus LMOB, Monteiro I, Sant’Ana MSSC, Trevisani VFM. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. Baak JPA, ed. PLOS ONE. 2017;12(7):e0179185. doi:10.1371/journal.pone.0179185

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Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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NOTE: This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.