Needling of Tendons/Ligaments is Not a placebo
Chronic Low Back Pain
Coccyx Pain After Fracture
Degenerative Disc Disease
Needling of Tendons/Ligaments is NOT a placebo: Puncture of Cell membrane with inflammatory lipid release.
In the treatment of low back pain there are four treatment comparison studies. The control group in all back studies involved needle contact with attachments of ligaments and tendons. By injecting ligaments and tendons, there is needle contact with cell membranes of connective tissue cells. Disrupting cell membranes releases lipids, which in turn cause signaling of fibroblasts.Needling of Tendons is NOT a placebo: Microbleeding with platelet effects.
In addition, microbleeding from needle contact is expected, and Edwards and colleagues have demonstrated the potential healing effect of whole blood injection in patients with recalcitrant tennis elbow. Edwards SG, Calandruccio JH: Autologous blood injections for refractory lateral epicondylitis J Hand Surg [Am] 28(2):272, 2003.
The hope is that future studies on low back pain will include a near-placebo arm that avoids connective tissue contact or blood effects and that standard injection methods will be used. In the treatment of low back pain, standard treatment methods are now taught in cadaver courses offered by the American Academy of Orthopedic Medicine. An example of such a near-placebo would be needle insertion through skin without contacting bone or ligament.
Phenol + Dextrose: Wilkinson 2005. Treatment of Patients Referred for Back Surgery, Usually With Prior Back Surgery
Dr. Wilkinson, a neurosurgeon, performed a single blind study assigning patients with low back pain to either phenol/glycerine or anesthetic injection and demonstrated a better pain reduction with phenol/glycerine injection. The injection sites were not clearly described in his study and the patients required periodic injection. However they were patients with prior lumbar surgery (86%) and all had been referred for further back surgery. Only 4 out of 35 continued to pursue that option, with 29 out of 35 preferring periodic injections. Again, even though lidocaine is clearly not a control intervention, this study provides randomized and blinded assignment evidence that low back treatment with proliferant is better than with lidocaine alone.
Wilkinson HA Injection therapy for enthesopathies causing axial spine pain and the "failed back syndrome": a single blinded, randomized and cross-over study.: Pain Physician (United States), Apr 2005, 8(2) p167-73
ABSTRACT: BACKGROUND: Enthesopathies are a common cause of axial pain that is amenable to "minimally invasive" therapy. OBJECTIVE: To evaluate the effectiveness of injection therapy for enthesopathies. DESIGN: Single blinded, randomized, and cross-over study. METHODS: Thirty-five patients diagnosed as having painful enthesopathies as a major pain generator were studied. Of the patients studied, 86% of patients had undergone prior lumbar spine surgery and all were referred for neurosurgical evaluation for possible surgery. Patients were injected either with anesthetics alone or with anesthetics combined with phenol-glycerol proliferant prolotherapy. Outcomes were analyzed both clinically at the time of regular follow-ups, and by a series of multipart questionnaires. RESULTS: Patients received a total of 86 injections, 39 with local anesthetics, and 47 with prolotherapy. By clinical assessment patients obtained excellent to good relief of pain and tenderness after 80% of prolotherapy injections, but only 47% after anesthetics alone.
Dextrose: Hooper et al 2004., Treatment of Chronic Back Pain:
177 consecutive patients with chronic spinal pain were injected with dextrose 20% in facet capsule at affecteed levels as determined by palpation. (cervical, thoracic, lumbar) Iliolumbar and SI ligaments injected in those with low back pain. Weekly injection up to 3 within a 1 month period. Outcome measures included levels of pain, ADL and work ability on a 5 point scale each. 91% had reduced pain, 84% had improvement in work ability and 85% could do self care more easily. Hooper RA; Ding M Retrospective case series on patients with chronic spinal pain treated with dextrose prolotherapy Altern Complement Med (United States), Aug 2004, 10(4) p670-4
Chronic LBP DEX: Yelland et al 2004
The fourth RCT in chronic low back pain was reported in 2004 and designed by an experienced physician in Brisbane. Yelland MJ, Glasziou PP, Bogduk N, et al: Prolotherapy injections, saline injections, and exercises for chronic low-back pain: A randomized trial. Spine 29(1):9, 2004. This study, like the previous studies, had no placebo arm, but compared needling of ligament attachments to bone to doing the same thing but with dextrose 20% included in the solution. Substantial and sustainable important improvements in pain and function were demonstrated by both injection groups. Highlighted by this study is the importance of the beneficial effect of needling alone and that needling is not a placebo intervention.
Chronic LBP PDG: (Phenol Dextrose Glycerine) Dechow et al 1999
Incorrect injection sites along with failure to examine lead to worse rather than better outcomes. Dechow E, Davies RK, Carr AJ, et al: A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology 39:1255, 1999.
The third study on chronic low back pain was led by a chief investigator (rheumatologist) who had a mandate to "prove or disprove prolotherapy", was armed with a complete lack of knowledge of prolotherapy technique or referral patterns for ligament or tendon, and brilliantly, but probably unwittingly, designed the study to fail. Dechow E, Davies RK, Carr AJ, et al: A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatolgy 39:1255, 1999. Failure was insured by:
- Accepting patients with axial (back) pain only and excluding patients with leg pain referral.
- Finding a physician who was conversant with prolotherapy but preventing him from examining the patients for areas to inject. Rather the physician was forced to inject only specified areas.
- Allowing treatment only on ligaments that would cause leg pain and not any ligaments that would treat axial (back) pain, and .
- Injecting inflammatory (phenol-based) proliferant in these incorrect areas.
As a consequence of injecting inflammatory solution in completely wrong areas, this study is recorded as a prolotherapy study in which the active group did worse than the control. This study is worthy of inclusion in a discussion of back pain studies because of what it says about study design in musculoskeletal medicine. IE: It trumpets the importance of knowing anatomy, and referral patterns in connective tissue, and of hands-on examination.
Chronic LBP PDG: Klein et al 1993
Near significant (P = .056) evidence for superior effect of the inflammatory proliferant solution anesthetic needling (Klein et al) in chronic low back pain. Klein RG, Bjorn CE, DeLong B, et al: A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic low back pain. J Spinal Disord 6:23, 1993. See below
Chronic LBP PDG: Ongley et al 1987
Significant (P < .001) evidence for superior effect of the inflammatory proliferant solution over saline needling in chronic low back pain. Ongley MJ, Klein RG, Dorman TA, et al: A new approach to the treatment of chronic low back pain. Lancet 2:143, 1987.
Despite better-than-placebo improvement in the control group, the first two blinded studies of chronic low back pain (using phenol/dextrose/glycerin as active solution) demonstrated significant (P < .001) Ongley MJ, Klein RG, Dorman TA, et al: A new approach to the treatment of chronic low back pain. Lancet 2:143, 1987. and near significant (P = .056) Klein RG, Bjorn CE, DeLong B, et al: A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic low back pain. J Spinal Disord 6:23, 1993. evidence for superior effect of the inflammatory proliferant solution over saline needling (Ongley et al) and anesthetic needling (Klein et al). These two studies were weakened somewhat by multiple simultaneous treatments, although the injection solution was the only significant difference between the two groups.
Coccyx Pain: Dex Khan et al 2008.
Chronic pain in coccyx (coccygodynia) after coccyx fracture. Treatment of coccygodynia after fracture was the subject of a consecutive patient study recently published in the Journal of Orthopedic Surgery. 30 out of 37 patients with chronic non-responding coccygodynia responded to 2 injections of 20% dextrose. The recommendation was a trial of dextrose prolotherapy prior to proceeding to coccygectomy. Khan SA; Kumar A; Varshney MK; Trikha V; Yadav CS: Dextrose prolotherapy for recalcitrant coccygodynia [In Process Citation] J Orthop Surg (Hong Kong) (China), Apr 2008, 16(1) p27-9.
ABSTRACT: PURPOSE. To present the results of dextrose prolotherapy undertaken for chronic non-responding coccygodynia in 37 patients. METHODS. 14 men and 23 women (mean age, 36 years) with chronic coccygodynia not responding to conservative treatment for more than 6 months were included. 27 of them had received local steroid injections. A visual analogue score (VAS) was recorded for all patients before and after injection of 8 ml of 25% dextrose and 2 ml of 2% lignocaine into the coccyx. In 8 patients with a VAS of more than 4 after the second injection, a third injection was given 4 weeks later. RESULTS. The mean VAS before prolotherapy was 8.5. It was 3.4 after the first injection and 2.5 after the second injection. Minimal or no improvement was noted in 7 patients; the remaining 30 patients had good pain relief. CONCLUSION. Dextrose prolothearpy is an effective treatment option in patients with chronic, recalcitrant coccygodynia and should be used before undergoing coccygectomy. Randomised studies are needed to compare prolotherapy with local steroid injections or coccygectomies. Department of Orthopaedics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Degenerative Discs: Dextrose: Miller et al 2006: Treatment of severely degenerative discs.
Note that the great majority of the time the pain source is not the disc, and treatment of the paraspinal /paradiscal ligaments/tendons eliiminates pain. However some pain is from the disc as well in a portion of the patients. 25% dextrose injected in severely degenerative lumbar discs (too severe for IDET) with multiple tears reduced pain in a durable manner. Effects were quick enough to suggest a neurolytic mechanism via hypertonicity or other (IE neovessel) mechanisms. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician 2006 9:115-121.
Note that this study, although involving high concentration (Hypertonic) dextrose, was not intended in its conception as a study of prolotherapy, but primarily because a prolonged nerve blocking effect (neurolysis) of markedly hypertonic solutions was propsoed. Improvement in these patients was too quick (hours to days) to be explained on the basis of regeneration effects on the disc. The durability of improvement was potentially related however to regeneraive effects of the intradiscal dextrose.
Note also that this study was only for severe degenerative discs (discs with severe tears) and is a pilot study, meaning much more work needs to be done to determine what solutions are best for direct disc injection. The great majority of the time disc treatment is not necessary because prolotherapy for supportive structure will eliminate or improve pain sufficiently. This study examined only patients with particularly severe discs in patients not responsive to prolotherapy of supportive structures. Therefore results in unscreened patients without prolotherapy on other spinal structures first, may not be comparable. To view this study click here: DiscInjectionStudy06.pdf
Here is the abstract:
Background: Degenerative discs are thought to produce nerve root pain either mechanically or chemically. Particularly in the case of advanced degenerative disc disease, this clinical entity has often proven to be symptomatically resistant to peridural steroids, Intra-discalElectrothermoplasty (IDET) and direct surgical intervention. Exposure of irritated nerves to hypertonic dextrose is thought to have chemoneuromodulatory potential. Sustained pain reduction has been demonstrated in a pilot study involving injection of a combination of dextrose, glucosamine, chondroitin and dimethylsulfoxide into degenerative discs of patients with chronic low back pain of discogenic origin.
Objective: To assess the effects of disc space injections of hypertonic dextrose in patients experiencing chronic advanced degenerative discogenic leg pain, with or without low back pain.
Study Design: Prospective consecutive patient series. Methods: Patients with moderate to severe degenerative disc disease without herniation and with concordant pain reproduction with CT discography were included. All had failure of a physical therapy trial and substantial but temporary relief with two fl uoroscopically guided epidural steroid injections. Patients underwent bi-weekly disc space injection of a solution consisting of 50% dextrose and 0.25% Bupivacaine in the disc(s) found positive on discography. The study was performed in an out-patient surgery center in the United States. Outcome measures included an 11-scale numeric pain score (0-10).
Results : Each patient was injected an average of 3.5 times. Overall, 43.4% of patients fell into the sustained improvement group with an average improvement in numeric pain scores of 71%, comparing pretreatment and 18 month measurements.
Conclusion: The results suggest that intradiscal injection of hypertonic dextrose may have a place in the management of pain arising from advanced lumbar degenerative disc disease. Key Words: Degenerative disc disease, internal disc disruption, dextrose discogenic pain, discography
MISC1: Klein et al 2003. Treatment of Degenerative Disc Disease
Glucosamine, chondroitin, hypertonic dextrose and dimethylsulfoxide injected in degenerate lumbar discs with confirmed pain imitation on discography. Disability scores (Roland Morris) improved from 12.0 to 6.4, pain scores (VAS) improved from 6.11 to 3.00 on average. 43% did not improved but the 57% that did improved markedly with 72% improvement in disability scores and 76% in pain. Klein RG, Eek BCJ, O’Neill CW, Elin C, Mooney V, Derby RR. Biochemical injection treatment for discogenic low back pain: a pilot study. The Spine Journal 3 2003; 220-226.
Sacroiliac Pain: Dextrose: Cusi et al 2008: Dextrose injection markedly improves laxity testing of the SI joint.
25 consecutive patients with chronic low back pain localized to the SI joint region (posterior superior iliac spine) and positive on examination test for sacroiliac laxity/pain source were treated with 3 injections at 6 week intervals using 17% dextrose with CT guidance in the ligament and specifically not inside the joint itself. 12 month followup data revealed that the SI laxity maneuver score improved from a mean of 7.2 to 2.2 at 1 years (p < .001), the Quebec Pain Disability Scale improved from 57.7 to 39.5 (p = .002), the Roland Morris Back Pain Questionnaire improved from 13.3 to 7.2 (p = .001) and the Roland Morris Multi Form Questionnaire improved from 146.5 to 108.6 to 12 months. (P = .016) Cusi M; Saunders J; Hungerford B; Wisbey-Roth T; Lucas P; Wilson S. The use of prolotherapy in the sacro-iliac joint. [E pub ahead of print] Br J Sports Med (England), Published On line Apr 9 2008, doi:10.1136/bjsm.2007.042044.
Other comments: The clinical history requirements to determine SI source of pain and mechanical dysfunction were the following:1. Localized and/or radiating low back or buttock pain in the vicinity of the posterior superior iliac spine, 2. Worse pain on loading positions such as standing, sitting, walking or negotiating stairs, and 3. 6 months of pain.
9 physical exam factors were looked at and scored to determine candidacy with maximum score of 9 and minimum score not mentioned. The diagnosis had to be made independently by a SEM physician (MC, JS) and a physiotherapist (BH, TWR) involved in the study. The minimum number was not mentioned. The tests were the sacroiliac joint (SIJ) glide test (antero-posterior and vertical arm, with and without self bracing) , posterior pelvic pain provocation test (PPPP) , active straight leg raise (ASLR) [13-15] with and without self bracing and external manual compression and stork support (Gillett) test . A score of one was given for each positive finding. Clinical tests were therefore not graded. Maximum score was nine. Exercise program apparently continued that patient had performed with no sustainable benefit.
The amount injected was unclear with 0.8 ml was injected under CT guidance, but several injections along the ligament noted and a volume of 4 ml of approximately 17% dextrose in bupivicaine.
It is not clear if the study was truly consecutive. There were no controls. 25 patients were mentioned but only 19 had 3 month followup data gathered and the body of the paper was not clear why the 3 month followup point was not reached in all cases.
The authors make the point that previous studies on treatment of back pain with proliferant injection did not consider a specific clinical diagnosis. In contrast, if injury to specific structures, such as ligaments or fascia, can be related to a specific clinical presentation and subsequent loss of function associated with pain, the potential for measuring outcome with repeatable physical exam measures may be present. Standardization of those examination measures may be important
Here is the abstract:
Cusi M; Saunders J; Hungerford B; Wisbey-Roth T; Lucas P; Wilson S. The use of prolotherapy in the sacro-iliac joint. [E pub ahead of print] Br J Sports Med (England), Published On line Apr 9 2008, doi:10.1136/bjsm.2007.042044. ABSTRACT: OBJECTIVE: To determine whether prolotherapy is effective in the treatment of deficient load transfer of the SIJ. DESIGN: A prospective descriptive study. SETTING: Authors' private practice. PARTICIPANTS: 25 patients who consented to treatment and attended for at least one follow up visit and assessment. STUDY PERIOD: :From April 2004 to July 2007. INTERVENTION: Three injections of hypertonic dextrose solution into the dorsal interosseous ligament of the affected SIJ, under CT control, six weeks apart. MAIN OUTCOME MEASURES: Quebec Back Pain Disability Scale, Roland Morris 24, Roland Morris 24 Multiform questionnaires and clinical examination by two authors independently. Clinical tests include active straight leg raise, sacroiliac joint glide, Stork (Gillet), stance phase and posterior pelvic pain provocation tests. RESULTS: All patients included in this study attended for at least one follow up visit at 3, 12 or 24 months. The number of patients at follow up decreased at 12 and 24 months. Functional questionnaires demonstrated significant improvements for those followed up at 3, 12 and 24 months (p < 0.05). Clinical scores showed significant improvement from commencement to three, 12 and 24 months (p < 0.001). CONCLUSIONS: This descriptive study of prolotherapy in private practice has shown positive clinical outcomes for the 76% of patients who attended the 3 months and 12 months' follow up visits and for the 32% of patients who attended follow up visits at 24 months. Similar results were found in the Questionnaires (Q, RM and RMM) at 3, 12 and 24 months. The findings of this study warrant further research. Trial registration Written informed consent was obtained from all participants in the trial. This was conducted as a practice quality assurance project, and as such did not require ethics approval or trial registration.