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» Summary» Procedure Codes
» Description» Selected References
» Prior Approval» Policy History
» Policy

Medical Policy: 02.01.18 
Original Effective Date: November 1996 
Reviewed: December 2014 
Revised: December 2014 

Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.


Prolotherapy, also referred to as regenerative injection therapy and proliferation therapy, refers to a procedure performed to strengthen the lax or injured ligaments by injecting proliferating agents/sclerosing solutions directly into torn or stretched ligaments. The mild inflammatory response that is created by the injection promotes growth of new ligament or tendon fibers, resulting in a tightening of the weakened area.  It is proposed that additional treatments of prolotherapy, over a period of a few weeks, allow a gradual buildup of tissue to restore the original strength to the area and  may relieve pain. 


Prolotherapy may involve a single or a series of injections of the proliferating agent, which are often diluted with a local anesthetic.  Agents used for prolotherapy include zinc sulfate, psyllium seed oil, combinations of dextrose; glycerin; and phenol or dextrose alone. Polidocanol and sodium morrhuate, vascular sclerosants, have also been used to sclerose areas of high intratendinous blood flow associated with tendinopathies.


Guidelines on chronic pain from the American College of Occupational and Environmental Medicine (2008) have concluded that the use of prolotherapy for neuropathic or myofascial pain is not recommended.


Guidelines on low back pain from the American College of Occupational and Environmental Medicine (2007) have concluded that the use of prolotherapy for acute, subacute, chronic or radicular pain syndromes is not recommended.


American College of Occupational and Environmental Medicine (2011) guidelines on hand, wrist, and forearm disorders were unable to make a recommendation about the use of prolotherapy because of insufficient evidence.


European Commission Research Directorate General (ECRDG): A 2004 ECRDG Working Group that developed guidelines for the treatment of chronic low back pain concluded that there was strong evidence that prolotherapy is not an effective treatment for nonspecific chronic low back pain. Therefore, the Working Group recommended against use of prolotherapy for this disorder.


Prior Approval: 


Not applicable



Prolotherapy is considered investigational for all applications.


The literature consists of small randomized trials on a variety of pain syndromes with inconsistent results. The body of scientific evidence does not permit conclusions concerning the effect of prolotherapy on health outcomes for chronic neck or back pain, tendinopathies of the upper or lower limbs, osteoarthritic pain, or other musculoskeletal pain conditions. Therefore, prolotherapy is considered investigational for all indications.


Procedure Codes and Billing Guidelines: 

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • M0076 should be used for reporting prolotherapy. The code includes the charges for proliferatives.


Selected References: 

  • Medicare Coverage Issue Manual, 35-13. Prolotherapy, joint sclerotherapy, and ligamentous injections with sclerosing agents- not covered.
  • Reeves, K.D., Hassanein, K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and trapeziometacarpal) joints: Evidence of clinical efficacy. The Journal of Alternative and Complementary Medicine 2000; vol 6, No 4: 311-320.
  • Reeves, K.D., Hassanein, K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. The Journal of Alternative and Complementary Medicine 2000; vol 6, No.2: 68-7. 
  • Hauser, R.A. Punishing the pain - Treating chronic pain with prolotherapy. Rehab Management Feb/March 1999;26-30.
  • Dechow E, Davies RK, Carr AJ, Thompson PW. A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology (Oxford) 1999 Dec;38(12):1255-9. 
  • Tsatsos G, Mandal R. Prolotherapy in the treatment of foot problems. J Am Podiatr Med Assoc 2002 Jun;92(6):366-8.
  • ECRI. Prolotherapy for ligament or tendon pain. Plymouth meeting (PA): ECRI Health technology Information Service; 2004 May 14. 8 p. (ECRI Hotline Response). Also available: http//
  • Linetsky, F. S., Miguel, R., and Torres, F. Treatment of cervicothoracic pain and cervicogenic headaches with regenerative injection therapy. Curr Pain Headache Rep. 2004;8(1):41-8.
  • Kim WM, Lee HG, Jeong CW et al. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med 2010; 16(12):1285-90.
  • Scarpone M, Rabago DP, ZZgierska A et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med 2008; 18(3):248-54.
  • Rabago D, Best TM, Zgierska A et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet rich plasma. Br J Sports Med 2009; 43(7):471-81.
  • Robago D, Zgierska A, Fortney L, et al. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012 Apr;18(4):408-14.
  • Carayannopoulos A, Borg-Stein J, Sokolof J, et al. Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial. PM R. 2011 Aug; 3(8): 706-15.
  • Refai H, Altahhan O, Elsharkawy R. The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 2011 Dec; 69(12): 2962-70.
  • CMS. National Coverage Determniation (NCD) for Prolotherapy, Joint Sclerotherapy and Ligamentous Injections with Scelorosing Agents (150.7).
  • UpToDate. Epicondylitis (Tennis and Golf Elbow). Neeru Jayanthi M.D.. Topic last updated January 13, 2014.
  • UpToDate. Subacute and Chronic Low Back Pain: Nonsurgical Interventional Treatment. Roger Chou M.D.. Topic last updated December 5, 2013.
  • UpToDate. Treatment of Acute Low Back Pain. Christopher L. Knight M.D., Richard A. Deyo, M.D., MPH, Thomas O. Staiger, M.D., Joyce E. Wipf, M.D,, Topic last updated September 26, 2013.
  • UpToDate. Overview of the Management of Overuse (Chronic) Tendinopathy. Karim Kahn, M.D., Alex Scott, PhD, RPT.
  • American Association of Orthopaedic Medicine (AAOM). Position Statement. Prolotherapy for the Treatment of Back Pain. Available at:
  • American College of Occupational and Environmental Medicine (ACOEM). NGC: 9327. Low back disorders. Occupational medicine practice guidelines: evaluation and management of common health problems and functional recovery in workers. 2nd ed. 2007. Available at:
  • European Commission Research Directorate General (ECRDG) [website]. European Guidelines for Management of Non-specific Low Back Pain. 2004. Updated June 14, 2005. Available at:


Policy History: 


Date                                       Reason                                Action

August 2011                          Annual review                      Policy renewed

June 2012                             Annual review                      Policy renewed

May 2013                              Annual review                      Policy renewed

February 2014                        Annual review                      Policy renewed

December 2014                      Annual review                      Policy revised


Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.

Contact Information
New information or technology that would be relevant for Wellmark to consider when this policy is next reviewed may be submitted to:
  Wellmark Blue Cross and Blue Shield
  Medical Policy Analyst
  P.O. Box 9232
  Des Moines, IA 50306-9232
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