Home About us Editorial board Ahead of print Current issue Archives Submit article Instructions Subscribe Search Contacts Login 
  • Users Online: 611
  • Home
  • Print this page
  • Email this page

 Table of Contents  
Year : 2018  |  Volume : 30  |  Issue : 4  |  Page : 402-406

Resurrecting the antique system: Unraveling prolotherapy

Department of Oral Medicine and Radiology, Asan Memorial Dental College and Hospital, Chengalpattu, Chennai, Tamil Nadu, India

Date of Submission23-Jul-2018
Date of Acceptance02-Oct-2018
Date of Web Publication17-Jan-2019

Correspondence Address:
Dr. Sundar Shreenivas
Department of Oral Medicine and Radiology, Asan Memorial Dental College and Hospital, Asan Nagar, Keerapakkam, Chengalpattu, Chennai - 603 105, Tamil Nadu
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiaomr.jiaomr_127_18

Rights and Permissions

Proliferation therapy, or “prolotherapy,” is a simple, natural technique that stimulates the body to repair chronically damaged ligaments and tendons. Since 1930s, this technique has been used to stabilize injured joints and to relieve joint pain. Recently, it has also been used to treat temporomandibular joint (TMJ) dysfunction and considered as an effective therapeutic modality that reduces TMJ pain. Injection of prolotherapy agents into the joint space causes cells to grow and produces an increase in the growth factors with additional antibacterial effect. It is considered as a long-term solution rather than a palliative measure and should be considered before the use of long-term drugs or surgery. This article reviews the history and scientific literature regarding prolotherapy and its application in TMJ disorders.

Keywords: Growth factors, inflammation, pain, prolotherapy, temporomandibular joint

How to cite this article:
Shreenivas S, Sudhakar S, Senthil B. Resurrecting the antique system: Unraveling prolotherapy. J Indian Acad Oral Med Radiol 2018;30:402-6

How to cite this URL:
Shreenivas S, Sudhakar S, Senthil B. Resurrecting the antique system: Unraveling prolotherapy. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Jun 26];30:402-6. Available from: http://www.jiaomr.in/text.asp?2018/30/4/402/250248

   Introduction Top

Pain and dentistry go hand in hand, as it is one of the most common elements that bring the patient to a dental healthcare provider. According to International Association for the Study of Pain, pain is defined as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”[1] Pain can either be acute or chronic depending on the duration and the severity of pain. Acute pain is an attention-seeker, which will force the individual to seek a healthcare professional to alleviate pain immediately, whereas management of chronic pain is often viewed as a low priority among healthcare providers as it is considered as complicated, time-consuming, and often ineffective.[2]

Musculoskeletal disorders are the most common cause of chronic pain experienced by adults.[3] In the orofacial region, the term temporomandibular disorders (TMDs) is a collective term embracing a number of clinical problems that involve the masticatory muscles, the temporomandibular joints (TMJs), and associated structures, or both.[1] These disorders are characterized by pain at the TMJ, generalized orofacial pain, chronic headaches and ear aches, jaw dysfunction, including hyper- and hypo-mobility, limited movement or locking of the jaw, painful clicking or popping sounds with opening or closing of the mouth, and difficulty in chewing or speaking.[4]

The treatment modalities of TMJ pain include conservative and surgical management. The initial management of TMJ pain with surgical intervention would result in both physical and mental trauma to the patient. Hence, the forefront management of TMJ pain is through conservative approach, which includes resting the jaw, relaxing the jaw muscles, and jaw exercises as recommended by physical therapist along with dietary modifications and analgesics.[4] When all the conservative management techniques have failed or no significant outcome is obtained, prolotherapy can be an effective modality. Prolotherapy is a new novel approach for the treatment of TMDs apart from conservative and surgical management that has been gaining popularity in dentistry.

   Definition Top

Prolotherapy, as defined by Webster's Third New International Dictionary, is “the rehabilitation of an incompetent structure, such as a ligament or tendon, by inducing the proliferation of cells.” The word “Prolos” means growth. Prolotherapy injections cause proliferation or stimulation of growth of new, normal ligament and tendon tissue.[5] Of late, in 2007, Reeves defined prolotherapy as an injection of growth factors or growth factor production stimulants to grow normal cells or tissue.[5]

   History of Prolotherapy Top

Around 2500 years ago, Hippocrates treated athlete's shoulder instability by promoting healing through inflammation and strengthening of capsule of the shoulder using a red-hot needle Cautery.[4] In the 1930s, Louis W. Schulz described the strengthening method of the TMJ capsule by irritant solutions.[6]

Earl Gedney (1937) was the first to describe the treatment of ligament pathology by injection of irritants in unstable painful knee and sacroiliac joints.[7] Gustav Hemwall and George S Hackett were pioneers of this therapy. In 1939, George Hackett, a general surgeon, made the observation that “injections made at the junction of the ligament and bone resulted in profuse proliferation of the new tissue at this union.”[7]

George Hackett, in 1955, published the first experimental research on animal ligaments injected with irritating solutions, demonstrating the ability to induce hypertrophy and hyperplasia within connective tissue. In 1956, Hackett concluded that “sclerotherapy” implied “scar formation,” and instead, he introduced the term, “fibro-proliferative therapy” or “prolotherapy” as “the rehabilitation of an incompetent structure by generation of new cellular tissue.”[7]

   Mechanism of Action Top

The mechanism of action of prolotherapy is based on “inflammation secondary to injury” that initiates the biological process of wound healing [Figure1].

Prolotherapy works by causing a transient low-grade inflammation at the site of ligament or tendon weakness [fibro-osseous junction (FOJ)] thus “deceiving” the body into initiating a new healing cascade. Inflammation stimulates fibroblasts to the area, which synthesize precursors to produce mature collagen thereby reinforcing the connective tissue. This inflammatory stimulus raises the level of growth factors to resume or initiate a new connective tissue repair. The prolotherapy solution stimulates the proliferation of the fibroblasts originating from the periosteum. Fibrous connective tissue in the periosteum contains osteoprogenitor cells (preosteoblasts) that are capable of laying down reparative bone at the FOJ, which further strengthens the connective tissue attachment.[8],[9]

The three types of prolotherapy are as follows:

  1. Growth factor injection prolotherapy: injection of specific growth factor that begins growth of a certain cell line (example: erythropoietin)
  2. Growth factor stimulation prolotherapy: injection of certain substances induces the body to produce growth factors, for example, non-inflammatory dextrose (10%).[2] Human cells exposed to 0.3% dextrose can produce the growth factors such as platelet-derived growth factor, basic fibroblast growth factor, connective tissue growth factor, epidermal growth factor, and transforming growth factor-beta.[5]
  3. Inflammatory prolotherapy: the inflammatory signals that result from solutions have a growth factor stimulation effect, but they cause a more vigorous response, for example, 12.5%–25% dextrose, sodium-morrhuate-containing solutions and phenol-containing solutions.[6] It is an inexpensive medical technique for stimulation of the natural wound healing cascade.[5]

Injection technique

Patient posture and head position

The preferred patient position is supine or reclined posture to provide stability to head and to decrease the risk of syncope. The head is turned to the opposite side away from the injection site.

Preinjection procedure and selection of injection tools

Before administering injection, the anatomic landmarks are marked after cleaning the related skin area with appropriate antiseptic. A 3-cc syringe with 30-gauge needle and 1-inch length is preferably chosen [Figure 2]a.
Figure 2: (a) Pre – injection site preparation (b) Point of entry of the needle (c) Initial direction of the needle (d) Final needle direction

Click here to view

Articular injection approach

   Patient Position, Needle Position, Injection Frequency, and Protocol Top

Access to the superior joint space is achieved by asking the patient to close the anterior teeth on a small bite block or 2 thickness of dental cotton rolls which enables translation of the mandibular condyles down to the glenoid slope of the anterior fossa [Figure 2]a.

The needle is penetrated on to the skin midway between tragus of ear and posterior aspect of condyle [Figure 2]b. It is then directed superiorly and anteriorly toward the apex of the fossa into the superior joint space where a contact is established with the periosteum. When a contact is made with periosteum into the joint capsule, a slight momentary resistance is felt. If excessive resistance is felt, then the needle is withdrawn slightly and redirected to ensure that the injection is superficial to but in contact with periosteum [Figure 2]c and [Figure 2]d.

The second target is an area where the disc attaches to the superior portion of the lateral pterygoid muscle that commonly produces spasm in chronic disc displacement. Strengthening of the tendinous attachment of the muscle to the disc is accomplished by injecting the solution. The anesthetic component of the solution allows the disc to reposition itself over the condyle and often produces an immediate reduction in TMJ clicking.[10]

Post-injection bleeding and protocol

The injection site is observed for bleeding after needle withdrawal. Generally, the bleeding is minimal and direct pressure stops the bleeding within seconds. A similar procedure is repeated on the opposite side if it is affected. The patient is allowed to rest for a short interval. The pulse is recorded. Patient's comfort is assured and reappointment is scheduled.[6]

Frequency of injection

Early prolotherapy injections were given at weekly intervals, but there was no evidence of benefit from more frequent injections. A common prototypical schedule is to inject 3 cc of the solution at second, fourth, and sixth week intervals, over a total of 12 weeks. Fibrous tissue proliferation may continue as long as several months following the injections.[6]


The various injection solutions used in prolotherapy are called as proliferant solutions. The ultimate goal of injection therapy is to initiate inflammation and wound healing, and thus stimulate the formation of a new ligament or tendon. The classification of proliferants and their mechanism of action are elaborated in [Table 1].[2],[3],[4],[5],[7],[10],[11]
Table 1: Proliferants with their mechanism of action

Click here to view

Potential complications

Post-injection morbidity following prolotherapy is more likely to result from faulty injection techniques rather than from the proliferant solutions.

Common transient complications following local anesthesia are as follows:

  1. Local anesthetic effect makes the patient more susceptible to biting the tongue or buccal mucosa in that region[2]
  2. Speech may be altered until the anesthetic effect is worn-off.[5]

Other common complications include the following:

  1. Discomfort during the procedure
  2. Temporary anesthesia that may extend as far as the eye and cause ptosis
  3. Extravasation with external bleeding and/or visible facial bruising
  4. Anxious patients occasionally report dizziness and are at risk of syncope, which can be minimized by supine positioning of the patient during the procedure.[10]

Pre- and postoperative instructions for prolotherapy[2],[5]

  1. A signed informed consent is obtained from the patient
  2. Ask the patient to take semisoft diet until the posterior occlusion is reestablished; usually in 2–3 days and to avoid rubbing, scratching, or irritating the anesthetized zone
  3. Eye drops may be necessary in cases of ptosis, for a few hours or until the eyelids regain motility
  4. Since prolotherapy effects are dependent on reestablishing a localized inflammation, ice and anti-inflammatory medications must be avoided for at least several weeks after the injections
  5. Acetaminophen and opioid analgesics can be prescribed for the post-injection discomfort and to help manage coexistent pain disorders.


  1. A tendinous or ligamentous injury
  2. Pain in the joints under load during function
  3. Failure of oral appliances
  4. In refractory cases where conservative management have failed
  5. Patients in whom surgical management is not possible
  6. To enhance recovery as an adjuvant to other treatment procedures such as oral appliances.


  1. Allergy to the components of prolotherapy solution
  2. Active state of infection
  3. Patient on anticoagulant medication
  4. Healing disorder
  5. Bleeding disorders, for example, hemophilia
  6. Malignant condition
  7. Existence of parafunctional habits
  8. Septic arthritis.

   Prolotherapy in TMJ Disorders: Evidence-Based Approach Top

Prolotherapy is usually implemented in chronic musculoskeletal joint disorders where other modalities have failed and surgery is the only option. Extensive studies are done and satisfactory results were obtained for prolotherapy in knee osteoarthritis, finger osteoarthritis, rotator cuff tendinopathy, lateral epicondylosis, plantar fasciopathy, and nonsurgical sacroiliac pain but limited studies related to prolotherapy in TMJ disorders. Prolotherapy can be used in certain conditions of TMDs such as TMJ pain, disc displacements with or without pain, TMJ dislocations, chronic closed lock, Myofacial Pain Dysfunction Syndrome (masseter and temporalis) and in patients who are refractory to treatment of TMDs with an intraoral orthosis, dietary restrictions, physical therapy and other conservative homecare methods. Scientific evidences show that prolotherapy is an effective modality where significant improvements in mouth opening (ranging from > 50% pain reduction to complete remission), increased range of motion (with a maximum of 38 mm mouth opening), remission of TMJ clicking and reduced (91%), or complete remission of TMJ dislocation can be achieved. To the best of our knowledge, [Table 2] shows the studies associated with prolotherapy in TMJ disorders with their findings put together in a nutshell:
Table 2: Various studies showing the outcome of Prolotherapy in TMD's

Click here to view

   Conclusion Top

Prolotherapy can be used in refractory cases treated with medicines and where no satisfactory improvement is attained through physiotherapy or any other conservative modes of managements in TMDs. Although prolotherapy has been there for more than a decade, its implications in TMDs have not been highlighted much in dentistry when compared with other musculoskeletal joints. Further studies with more sample size have to be conducted to decide its effectiveness in treating TMDs.[15]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Greenberg MS, Glick M, Ship JA. Orofacial pain. In: Petrice C, editor. Burket's Oral Medicine, 11th ed. Ontario: BC Decker Inc.; 2008. p. 257-87.  Back to cited text no. 1
Jeelani S, Krishna S, Reddy J, Reddy V. Prolotherapy in temperomandibular disorders: An overview. Open J Dent Oral Med 2013;1:15-8.  Back to cited text no. 2
Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord 2016;9:139-59.  Back to cited text no. 3
Kumar AV, Jaishankar HP, Kavitha AP, Naik PR. Prolotherapy: A new hope for temporomandibular joint pain. Indian J Pain 2013;27:49-52.  Back to cited text no. 4
  [Full text]  
Vankdoth S, Reddy AS, Talla H, Vijayalaxmi N, Madhulatha G. Prolotherapy – A venturing treatment for temporomandibular joint disorder. IJSS Case Rep Rev 2014;1:27-30.  Back to cited text no. 5
Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med 2000;6:37-46.  Back to cited text no. 6
Trescot AM. Everything old is new again: Tech Reg Anesth Pain Manag 2015;19:14-8.  Back to cited text no. 7
Alderman D. Prolotherapy for golf injuries and pain. Pract Pain Manage 2008;1:56-64.  Back to cited text no. 8
Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care 2010;37:65-80.  Back to cited text no. 9
Hakala RV. Prolotherapy (proliferation therapy) in the treatment of TMD. J Craniomandibular Pract 2005;23:1-6.  Back to cited text no. 10
Rabago D, Yelland M, Patterson J, Zgierska A. Prolotherapy for chronic musculoskeletal pain. Am Fam Physician 2011;84:1208-10.  Back to cited text no. 11
Hauser RA, Hauser MA, Blakemore KA. Dextrose prolotherapy and pain of chronic TMJ dysfunction. Pract Pain Manage 2007;1:49-55.  Back to cited text no. 12
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 Maxilofac Surg 2011;69:2962-70.  Back to cited text no. 13
Zhou H, Hu K, Ding Y. Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation. Br J Oral Maxillofac Surg 2014;52:63-6.  Back to cited text no. 14
Hakala RV, Ledermann KM. Wonder why? The use of prolotherapy for temporomandibular joint dysfunction. J Prolother 2010;2:439-46.  Back to cited text no. 15


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

   Abstract Introduction Definition History of Prolo... Mechanism of Action Patient Position... Prolotherapy in ... Conclusion Article Figures Article Tables
  In this article

 Article Access Statistics
    PDF Downloaded129    
    Comments [Add]    

Recommend this journal