Degenerative Disc Disease Without Meric Pain Scores of 71%, Comparing Pre- Surgical Intervention

Miller et al • Intradiscal Injection of Hypertonic Dextrose 115 Pain Physician. 2006;9:115-121, ISSN 1533-3159 A Prospective Evaluation

Treatment of Painful Advanced Internal Lumbar Disc Derangement with Intradiscal Injection of Hypertonic Dextrose

Matthew R. Miller, DSc, PA-C, Robert S. Mathews, MD, PhD, and K. Dean Reeves, MD

Background: Degenerative discs are disc space injections of hypertonic dex- surgery center in the United States. thought to produce nerve root pain ei- trose in patients experiencing chronic ad- Outcome measures included an 11- ther mechanically or chemically. Particu- vanced degenerative discogenic leg pain, scale numeric pain score (0-10). larly in the case of advanced degenera- with or without low back pain. Results : Each patient was injected an tive disc disease, this clinical entity has Study Design: Prospective consecu- average of 3.5 times. Overall, 43.4% of pa- often proven to be symptomatically re- tive patient series. tients fell into the sustained improvement sistant to peridural steroids, Intra-dis- Methods: Patients with moderate to group with an average improvement in nu- cal Electrothermoplasty (IDET) and direct severe degenerative disc disease without meric pain scores of 71%, comparing pre- surgical intervention. Exposure of irritated herniation and with concordant pain re- treatment and 18 month measurements. nerves to hypertonic dextrose is thought production with CT discography were in- Conclusion: The results suggest that to have chemoneuromodulatory poten- cluded. All had failure of a physical ther- intradiscal injection of hypertonic dex- tial. Sustained pain reduction has been apy trial and substantial but temporary trose may have a place in the manage- demonstrated in a pilot study involving in- relief with two ﬂ uoroscopically guided epi- ment of pain arising from advanced lum- jection of a combination of dextrose, glu- dural steroid injections. bar degenerative disc disease. cosamine, chondroitin and dimethylsulf- Patients underwent bi-weekly disc Key Words: Degenerative disc dis- oxide into degenerative discs of patients space injection of a solution consisting of ease, internal disc disruption, dextrose, with chronic low back pain of discogen- 50% dextrose and 0.25% Bupivacaine in discogenic pain, discography ic origin. the disc(s) found positive on discography. Objective: To assess the effects of The study was performed in an out-patient

The intervertebral disc is a com- logic features of this pain entity. Recent gested that a reduction in proteoglycan plex structure that has become the fo- literature (2) has shed further light into synthesis leads to decreased produc- cus of much attention in clinical prac- this phenomenon and indicates the ex- tion and maintenance of the disc ma- tice and it has been suggested that de- istence of a biochemical/biomechanical trix, triggering the cascade of degener- generation of the intervertebral disc is model of lumbar discogenic pain. This ation (10). a major source of low back pain. The calls into question the popular belief Repetitive axial loading of the lum- concept of internal disc disruption, that a disc lesion can only cause pain bar intervertebral disc results in fatigue with and without herniation, was de- by direct nerve compression from disc failure, disruption of internal collagen scribed by Crock (1), who introduced herniation (3-6). Clinical studies have fibrils and progressive infiltration of the the concept and described the patho- shown that fewer than 30% and as few nucleus pulposus into the annular fi- as 1% of low back problems can be le- bers. Clinical and pathoanatomic inves- From: Lebanon Anesthesia Associates, Leba- gitimately ascribed to nerve root com- tigations, including discography, have non, Pennsylvania; Orthopedics of Lancaster, pression (7-9). shown that pathways frequently exist PSI, Lancaster, PA, and Department Of Physi- cal Medicine and Rehabilitation, University of Internal disc disruption is a pro- between the degenerative nucleus pulp- Kansas, Kansas City, KS. cess by which biochemical changes in- osus and the adjacent nerve root. Pain Address Correspondence: volving phospholipase A2, substance P can occur as a result of compression Matthew R. Miller, DSc, PA-C, 830 Tuck Street, and increased fibrinolytic activity ulti- or traction of nociceptive fibers within Lebanon, PA 17042 mately lead to degeneration. The aging the disc as well as by release of irritat- Email: [email protected] Conﬂ ict of Interest: None disc suffers progressive decline in nutri- ing chemical by-products through tears Disclaimer: There was no external funding in tion as a result of an alteration in dif- in the annulus fibrosis of the disc. The preparation of this manuscript. fusion, diminished blood supply at the precise pathophysiologic mechanism by Manuscript received on 3/20/2006 periphery of the annulus fibrosis and which chemical mediators within the Revision received on 3/30/2006 within the vertebral bodies, and de- intervertebral disc produce hyperalgesia Accepted for publication on 4/02/2006 creasing matrix water. It has been sug- is not clear. It has been speculated that

Pain Physician Vol. 9, No. 2, 2006 116 Miller et al • Intradiscal Injection of Hypertonic Dextrose there is proliferation of sensory nerve encing unrelenting pain. MRI examina- ical effect of dextrose has been validat- fibers containing calcitonin gene-relat- tion in these cases may reveal desicca- ed in the literature (23-25). Further, as ed peptide in the end-plate region and tive disc changes but no significant al- it was recognized that the physiologic vertebral body adjacent to the degener- teration in the outer disc contour. In the makeup of the disc annulus was greatly ative disc. The increase in the density of general population, these patients fail similar to fibrous connective tissue, the sensory nerves and the presence of car- to achieve an optimal response to pre- authors hypothesized that intradiscal tilage plate defects suggest a potential vailing non-operative therapies that in- injection of hypertonic dextrose might role of endplates and vertebral bodies as clude physical and manipulative ther- result in improvement of discogenic pain generators in patients with degen- apies as well as epidural steroid injec- pain in patients with moderately severe erative intervertebral discs (11). tions, zygapophysial and sacroiliac joint to severe degenerative lumbar interver- Weinstein et al (12) investigated injections. Further, due to severity of tebral discs who had failed conservative the pain reproduced by discography disc involvement, they tend to fall out- treatment efforts to that point. and concluded that sensitized annu- side of the known indications for intra- lar nociceptors may create symptoms discal electrothermoplasty (IDET) (9) METHODS via neurochemical changes within the and are often referred for surgical ar- The patient population was chosen disc. Kawakami et al (13) hypothesized throdesis or disc replacement. from consecutive patients evaluated for that these chemicals may be transported In addition to the wide variety of leg pain with or without back pain and into the axons of a nerve root and initi- existing interventional pain techniques, with normal neurological examination. ate production of inflammatory agents the present authors had been using hy- Duration of pain was not a hard re- such as prostaglandins, which may lead pertonic dextrose solution to treat pa- quirement, but proceeding through the to radicular pain. Byröd et al (14) dem- tients with spine pain complaints found evaluation and conservative treatment onstrated a direct transport route to the to be arising from the fibro-osseous process generally took six months. Pre- axons of the spinal nerve roots and sug- junctions (enthesis) of various tendons vious laminectomy/discectomy did not gested that the chemical produced in and ligaments, including the interspi- disqualify the patient as long as relief the epidural space may be able to alter nous, intertransverse, iliolumbar, sac- of symptoms for at least two years oc- the excitability of C fibers. roiliac, and multifidi muscles, as well as curred, with subsequent event-induced Low back and sciatic pain can be other tough soft tissue periosteal attach- exacerbation of symptoms. present even in the apparent absence ments. This treatment is based upon the All patients were given an explana- of distinct morphologic changes; con- principles of prolotherapy (Also called tion of the purpose of this study and an versely, many patients report no pain, regenerative injection therapy (RIT)). opportunity for discussion. They were even in the presence of marked degen- The Latin word proli means offspring. also advised of the associated risks and eration. The treatment of pain arising A current definition of prolotherapy is given the choice as to whether or not from the severely degenerative lumbar chemomodulation of collagen through re- they wanted to participate. Informed intervertebral disc is difficult and con- petitive stimulation of inflammatory and consent was then obtained. Appropriate troversial, with many patients failing proliferative phases in a sophisticated precautions were taken to protect the conservative treatment and ultimately process of tissue regeneration and repair, privacy and anonymity of all of the pa- requiring lumbar arthrodesis. However, mediated by numerous growth factors tients participating in this study. the significantly invasive nature of the leading to restoration of tensile strength, Initial work-up included history surgery combined with poor predict- elasticity, increased mass and load bear- and physical examination combined ability of pain relief often leads these ing capacity of connective tissue (20). In with weight-bearing plain film radio- patients to defer surgical intervention. vitro exposure of human cells to extra- graphs and CT or MRI. All patients There is increasing interest in the cellular dextrose concentrations as little were entered into a conservative treat- development of physiologic treatment as 0.6% (normal intracellular concen- ment program to include physical ther- options that address the underlying tration approximates 0.1%) leads to el- apy and/or chiropractic care as well as causes of disc degeneration and pain evation of as many as 15 different genes oral medication for symptom reduc- (15-19). Injection therapy is one such within minutes to hours of cellular ex- tion. Those patients that continued to alternative that places a symptom mod- posure, including those of key growth experience pain were selected for fur- ifier and/or repair stimulant directly factors (21, 22). ther study based upon a diagnostic/ into degenerated and painful lumbar The authors found that by increas- treatment algorithm created by the au- intervertebral discs. ing the (end) concentration of the dex- thors for this study (Fig 1). Patients with radicular leg pain trose to 20-25% in the injectate, pa- Thus, two fluoroscopically guid- with or without low back pain, suspect- tients were reporting improvement in ed epidural steroid injections were per- ed as being associated with evident sin- their pain complaints often after one formed two weeks apart. If this led to gle or multi-level moderately severe to injection into painful osteoarthrit- complete or near complete pain relief severe degenerative lumbar disc disease, ic knees, elbows, shoulders and carpo- (80-100%) followed by return of symp- demonstrate typically non-focal neu- metacarpal joints so as to suggest a che- toms, patients then underwent discog- rological examinations, yet are experi- moneuromodulatory benefit. This clin- raphy followed by CT scan to determine

Pain Physician Vol. 9, No. 2, 2006 Miller et al • Intradiscal Injection of Hypertonic Dextrose 117

Pt. c/o LBP and/or leg symptoms with H&P supported suspicion of discogenic pain source

Negative neurological exam

Failed 4-6 weeks conservative care (oral medication, physical and/or manipulative treatment, etc)

ESI X 2, 2 weeks apart with initial excellent relief then return of symptoms

Discogram with CT

Positive for concordant pain, CT shows diffuse internal derangement with multiple grade IV and V tears

Fig 1. Patient ﬂ ow diagram

a level-specific concordant pain genera- 4. No significant change in the outer 50:50 with bupivacaine 0.25% plain, to tor and to assess the disc morphology. contour of the disc (no significant a total volume of 3 mL. Thus the final The ultimate intent was to demonstrate bulge or frank HNP) concentration of dextrose in the injec- if pain from moderate to severe disc If extravasation of contrast had oc- tate became 25%. Injections were per- disease without significant disc bulge curred during the discogram for that formed bi-weekly under fluoroscopic or frank HNP would respond to hyper- particular patient, we expected that guidance and the needle insertion was tonic dextrose. Patients were enrolled subsequent therapeutic injection would on the side of greatest symptomatic in the study only if CT discography re- similarly extravasate. However, extrav- complaint. A single puncture of the disc vealed the following: asation only occurred in two patients was created using a 5 or 7 inch Becton 1. Concordant pain reproduction. with contrast volumes less than 3 mL Dickinson 22 gauge Quincke tip spinal 2. Negative pain production with during the discogram and in 14 pa- needle (single needle technique). One testing of at least one other level. tients with contrast volumes in excess half of the injectate was placed as close 3. CT evidence of multiple grade of 3 mL. to the center of the disc as the approach IV or V tears of the annulus fi- Prior to the first treatment, pa- window would allow based upon the lo- brosis (Fig 2) at one or more lev- tients filled out a 0-10 numeric pain cal anatomy. The remainder was inject- els, based on the modified Dallas scale (0 = no pain; 10 = maximal pain) ed into the estimated middle and out- criteria (26) indicating moderate, to describe the severity of their leg pain. er thirds of the disc, as the needle was moderately severe, or severe des- Then, they received an intradiscal injec- withdrawn. An average rate of injection iccative disc disease. tion of 50% dextrose in water, mixed was utilized, so as to allow the injectate

Pain Physician Vol. 9, No. 2, 2006 118 Miller et al • Intradiscal Injection of Hypertonic Dextrose

than six months (one at two months and the other three months). The average number of treatments was 3.5 (range 1 to 6) and the average number of discs treated was 1.7 (range 1 to 3). Patients were followed for a minimum of six months (6 to 41 months with a mean of 18 months) and were grouped for data analysis ac- cording to response pattern (Fig 3). Thirty-seven patients were non-responders with either less than 20% improvement (31/37) or a temporary flare of pain (6/37). Six were temporary responders, with return to baseline pain by the time of last contact. The duration of follow up had large variability (six weeks to 41 months) since non-responders did not receive treatment or extended follow-up after the third bi- weekly injection or after an injection followed by flare. Therefore, 43.4% (33/76) of patients showed a sustained treatment response. Fig. 4 displays numeric pain score data for responders at 0 and two months and at final follow- up. The mean numeric 0-10 (0= no Fig 2. Post discogram axial CT images of a normal disc (top left) and pain and 10=maximal pain) pain scale abnormal disc (top right)- Below are the same discs with computer contrast ratings and standard deviations were and color enhancement added to reveal separation of nuclear (red/dark 8.9 (S.D. 1.4) at study entry, 2.5 (S.D. gray) and annular (blue-green/light gray) regions. 2.0) at two months and 2.6 (S.D. 2.2) at 18 months in this group. The average improvement in the numeric pain to reasonably diffuse into the discal en- with each patient at six months follow- score was 71%. vironment (5-10 seconds). ing the initial treatment of the last pa- The average age of responders was Prior to each bi-weekly injection tient treated. very similar to the group as a whole the patients did again complete the 0- at 56 (29 to 90). The duration of pain 10 numeric pain scale. Treatment was RESULTS was similar, with a mean of two years halted after three injections if the pa- Between January 2001 and De- nine months. The average number of tients were non-responders (defined cember 2002, 76 out of 737 patients treatments was 3.9 (range 1 to 5) and as less than 20% improvement in pain with leg pain, with or without low the average number of discs treated scale), or if they experienced a signifi- back pain, were found to have con- was 1.7 (range 1 to 3). The durabili- cant exacerbation of pain that persist- cordant symptoms on discography ty of response was reflected in the av- ed until the time of the next scheduled and post discography CT with mod- erage number of treatments. Those injection, such that they were unwilling erate to severe desiccative disc disease. that stopped early did not require fur- to continue. Treatment was also halted Nine of these patients had previous- ther injection. Of the 33 responders, all if the pain rating reduced to 2 or less ly undergone successful laminectomy/ but four reached a pain score rating of following the second injection, expect- discectomy at one or more levels with 4 or less at final follow up. Since 33 of ing that further stabilizing effect would good relief for at least two years fol- 39 initial responders sustained a long- occur over time. Patients were offered lowed by a subsequent event-induced term response, patients who responded up to five treatments if they were ex- exacerbation of symptoms. There were to three injections were 85% likely (33/ periencing a progressive reduction in 41 males and 35 females. The age range 39) to sustain a long-term response. pain, but had the option of stopping of these patients was 21 to 90 years with Of the 37 non-responders, six had any time their response was considered a mean of 55 years. Duration of pain treatment halted due to a significant by them to be satisfactory. To ensure complaints ranged from 2-240 months pain exacerbation. Four of the six had a minimum of six months of follow- with a mean of 39 months. Only two pain resolve to baseline with pain med- up, phone or clinic contact was made patients in this group had pain less ication and a prednisolone dose pack

Pain Physician Vol. 9, No. 2, 2006 Miller et al • Intradiscal Injection of Hypertonic Dextrose 119

40 10

8 30

6 20 4

10 2

0 0 Non Temporary Sustained Baseline 2 Months 18 Months Responders Responders Responders Fig 3. Intradiscal dextrose response patterns Fig 4. Pain scores in responders within two weeks and two required tors. These growth factors (i.e., plate- relief demonstrated moderately severe intradiscal steroid injection with res- let derived growth factor, transform- to severe degenerative disc disease and olution of flare, to baseline, within six ing growth factor beta, basic fibroblast it is possible that the relief occurred weeks. growth factor, insulin like growth fac- because the discs were predominant- We observed no evidence of disc tor, and connective tissue growth fac- ly chemically sensitive. Those patients space infection, neurological sequelae, tor) are elevated by extracellular glu- experiencing initial relief of pain from or end plate fracture at any time in as- cose concentrations of 0.6% or great- the local anesthetic, with subsequent sociation with the diagnostic and treat- er (21, 22). The hyperosmolar nature return of that pain, may well have me- ment protocol. of the dextrose solution may be impor- chanically sensitive discs and the cur- tant as well. Exposure of a cell to an os- rent treatment regimen was insuffi- DISCUSSION molarity change as little as 50 mOsm cient due to treatment design flaws (in- A significant number of patients has also been found to activate en- adequate chemical concentration, in- obtained marked benefit promptly af- zymes (phosphate donors, also termed sufficient number of treatments, failure ter a single injection. Our treatment kinases) in human cells, which may to consistently direct medication to the solution of 50% dextrose/0.25 bupi- have growth effects (27-29). nociceptive fibers and other factors). vacaine has an end concentration os- Dextrose (D-glucose) has also Klein et al (17) studied the poten- molarity of approximately 1423 mOsm been found to have benefit in double tial benefit from the injection of a so- (1265 dextrose + 158.5 bupivacaine). blind studies on small and large osteo- lution comprised of glucosamine and Due to this high osmolarity, we hy- arthritic joints (24, 25). D-glucose, in chondroitin sulfate combined with hy- pothesize that the rapid onset of pain addition to increasing multiple growth pertonic dextrose and dimethylsulfox- relief is attributable to chemoneuro- factors, has been found to suppress ide (DMSO). This solution was inject- modulation of adjacent nociceptors. potential disrepair factors, including ed into degenerative lumbar discs of 30 The hyperosmolar solution may also such interleukins 2, 6 and 10 (30). El- patients suffering from chronic intrac- result in modulation of local vascular evated D-glucose concentrations in a table low back pain. These patients had hemodynamics, leading to a reduction joint also appear to reduce cartilage- previously failed conservative therapy in nociceptive activity. The exact mech- damaging-protein (collagenase) lev- and all demonstrated a positive disco- anism by which rapid improvement in els (31). Proving effects on ligaments gram at one or more levels as evidenced pain occurred is not known. By con- is more difficult. Ultrasound studies by concordant pain provocation com- trast, the demonstrated durability of are in pre-publication at this time to bined with morphologic disc abnor- response is not likely to be solely from demonstrate structural effects. Direct malities. Seven of these patients had chemoneuromodulatory effects. The machine measurement is difficult but failed to respond to IDET. A similar so- authors would suggest that sustained a sentinel study on anterior cruciate lution, though without the chondroitin benefit results from the growth factor ligament (ACL) ligament laxity with sulfate, was injected into the same level and tissue stabilizing effects of the dex- objective arthrometric measurement zygapophysial joints at the time of the trose upon the annulus fibrosus of the (KT-1000) demonstrated the ability of disc injection. Seventeen patients re- disc (17, 20). simple 10% dextrose injection to tight- ported an average reduction in the nu- Potential tissue stabilizing bene- en loose ACL ligaments (23). Clearly meric pain score of 76%, which is an fits of dextrose injection may occur in much work needs to be done on dem- encouraging result, given the nature of both cartilage and ligaments/tendons onstrating similar effects on interverte- the involved pathology. However, the since chondrocytes and fibroblasts re- bral disc structure. authors acknowledged that the deci- spond positively to similar growth fac- All patients that experienced pain sion to empirically treat the same level

Pain Physician Vol. 9, No. 2, 2006 120 Miller et al • Intradiscal Injection of Hypertonic Dextrose zygapophysial joints complicated their chemical irritants from within the disc. Discography induces pressures that ability to discern the relative contribu- However, pain relief derived from such differ from the pressure distribution of tion of the intervertebral disc and zyg- a mechanism would only be expected to normal activities, producing stimula- apophysial joints to the total pain per- last only as long as it took for the chemi- tion by means of an expanding force, ception for a given patient. Additionally, cal irritants to again coalesce, leading to with peak force on the nucleus pulpo- their use of a solution with several com- return of pain impulses over the relative sus. Normal activities involve compres- ponents limits the ability to measure short term. There appeared to be no re- sion forces with peak pressures occur- whether or not and to what extent each lationship between those patients who ring in the outer annulus. During nor- component contributes to the benefit. experienced temporary increases in mal activities over a range of loading The present authors chose to test pain associated with the dextrose, and conditions, the largest stresses in nor- the relative benefit of a single active whether they were responders or non- mal discs appear to occur in the annu- component in the treatment of a sin- responders. lus, not the nucleus (34). Thus, the re- gle known nociceptive source based From a technical point of view, lationship between distributed loads upon the patient presentation and CT discs with a notable loss of disk height upon the severely degenerated annu- discography results. The percentage of are not appropriate candidates for lus, resulting vertebral endplate defor- responders suggests that the disc alone IDET; in many, the increased degree of mation and resulting pain generation may act as a primary nociceptive source nuclear disorganization further serves may stretch the diagnostic limits of in the three joint complex and benefit to make intradiscal navigation diffi- discography in terms of patient selec- may not always require same level zyg- cult (33). Further, a degree of internal tion. However, no clearly good alterna- apophysial injection. One unanswered derangement generally beyond a dis- tive exists at this time and so it remains question for further study, therefore, crete posterior grade 3, as well as anteri- our best test. is a means by which we can deter- or or lateral tearing, will not tend to be mine which patients require treatment associated with an optimal result from CONCLUSION of the disc alone and which would re- IDET (15). Despite the localized nature The current work suggests that in- quire treatment of the entire three-joint of annular pathology of the IDET treat- tradiscal injection of hypertonic dex- complex. ed discs, the average reductions in pain trose may have a place in the manage- Although this study was more than were 2.4 in one study (9) and 1.8 in an- ment of pain arising from advanced double the size of an earlier pilot study other (16). The patients treated in the lumbar degenerative disc disease. To on 25% dextrose disc injection (32) this present consecutive patient collection have clear responders and non-represent work should also be considered had discs with grade 4 and 5 annular sponders suggests a manageable sub- only a pilot study as it was neither ran- tears, moderate, moderately severe and set of patients that can be identified domized, controlled, nor blinded. The severe loss of axial disc height and dif- by about 6-8 weeks post-treatment on- results will have to be validated through fuse contrast opacification of the disc set (3 injections at bi-weekly intervals a study of more stringent design. Such a on post-discogram CT. and 2 week follow-up). It is most en- construct is being developed and con- In looking at the relationship be- couraging that the reductions in nu- sideration has been given to utilizing tween the degree of disc degeneration meric pain scale scores were so firmly blinded randomization and patient evident on the post-discogram CT and maintained in patients with uniform- evaluation, a placebo group, a larger the degree of improvement from the ly moderate to severe disc desiccation patient base and treatment group and dextrose injections, we found no clear at an average of 18 months. Those pa- manometrically assisted discography. correlation. This is to say that there tients who experienced no appreciable The two patients that had pain less were patients with diffuse internal an- improvement from the treatment were than six months at the time of treat- nular derangement who experienced not worse in any sustained way. Fur- ment were still reporting 0-2/10 pain benefit from the injections and those ther defined study is clearly indicated ratings at 33 and 41 months, respec- who were no better. The key may lie in toward a better understanding of the tively. Patient # 1 was a 48-year-old the degree of nerve fiber in-growth as it pathophysiology of painful degenera- male who had received three serial in- relates to the degree of disc degenerative discs, through which the evolution jections of the previous laminectomy/ tion, the exact number and location of of pain management procedures and discectomy level (L4-5). Patient #2 was these fibers, and whether the fibers are related treatments will occur. a 50-year-old male, had no history of chemical or mechanical in type. Fur- The results represent our obser- surgery and received four serial injec- ther, discographic pain interpretation vations, by way of direct experience in tions at L4-5 and L5-S1, based upon the of discs of the type described in the this field and in consideration of exist- results of the discogram. study patient type is challenging due ing scientific literature. The described The authors considered that pa- to the degree of internal disc disconti- treatment protocol is not intended to tients experiencing significant improve- nuity and the prospect of false positive represent guidelines for treatment or a ment after only one injection may have and false negative results has been con- standard of care. benefited from the simple dilution of sidered.

Pain Physician Vol. 9, No. 2, 2006 Miller et al • Intradiscal Injection of Hypertonic Dextrose 121

knowledge update. Spine 2002; 35: rior cruciate ligament laxity: A prospec- AUTHOR AFFILIATION: 333-342. tive and consecutive patient study. Al- 11. Brown MF, Hukkanen, McCarthy ID, Red- tern Ther Health Med 2003; 9:58-62. Matthew R. Miller, D.Sc., PA-C fern DR, Battern JJ, Crock HV, Hughes 24. Reeves KD, Hassanein K. Randomized SP, Polak JM. Sensory and sympathet- prospective double-blind placebo-con- Lebanon Outpatient Surgery Center ic innervation of the vertebral endplate trolled study of dextrose prolotherapy 830 Tuck Street in patients with degenerative disc dis- for knee osteoarthritis with or without Lebanon, PA 17042 ease. J Bone Joint Surg Br 1997; 79:147- ACL laxity. Alt Ther Hlth Med 2000; 6: Email: [email protected] 153. 68-80. 12. Weinstein J, Claverie W, Givson S. The 25. Reeves KD, Hassanein K. Randomized Robert S. Mathews, MD, PhD pain of discography. 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Pain Physician Vol. 9, No. 2, 2006