[460] Klein RG, Mooney V, Derby RR, et al. “Biochemical injection treatment for discogenic low back pain: a pilot study” The Spine Journal 2003; 3:220-226

The Study | Experimental Blunders | Result | Discussion | Theory & Opinion

In 2003 an investigation was published that explored a new technique for the treatment of chronic discogenic lower back pain.   Klein et al. proposed that by injecting a ‘biochemical soup’ into diseased intervertebral discs and fact joints, they could “promote a reparative response” and lessen the patients pain and functional disability.

This pilot study (the first of its kind), unfortunately, called for the injection of both the disc AND both facet joints on an “empirical” (based on experience and not proven fact) basis?   This little ‘surprise’ (that the investigators empirically injected both facet joints with the ‘Biochemical Soup’) makes the title of this investigation quite misleading, as well as it ruins the study's attempt to determine the efficacy of 'Biochemical Injection' for the treatment of pure discogenic pain.   A better title would have been “Biochemical injection treatment for ‘chronic’ Low Back Pain.”   It also made it impossible to know, as the authors openly admitted, where exactly the patients’ chronic pain was coming from: the disc, the facets, or both.  

Anyway, despite this poor title choice and the ‘shot gun’ style approach to the delivery of the ‘biochemical soup’, the results were quite interesting in that there was a marked improvement (74%) within about one-half of the patients, although I believe that the benefits of this improvement can NOT be permanent. (6,7)

THE STUDY:

Thirty patients, all of whom had been suffering chronic back pain for an average of 8 years, (yes, 8 years) were entered into this non-blinded investigation.   This was admittedly ‘tough’ group of patients to treat, for they all had failed conservative care.   In fact, seven of the 30 patients (23%) were status-post failed IDET, and 6 of patients (20%) were status-post failed spinal surgery.

To describe their levels of pain and disability, all patients completed the ‘Roland-Morris Disability Questionnaire’ (1) and a standard ‘Visual Analogue Pain Scale’ (2) both before the ‘treatment’ and then again one year after the treatment.

After completion of the pain & disability assessment tools, all patients underwent provocation discography.   Although the criteria were not given, all patients tested positive for concordant (typical) pain at one level or more.        

Immediately after discography, all concordantly positive discs of all patients were given an initial intradiscal injection of a “ disc solution” which consisted of the following components: 0.5% chondroitin sulfate, 20% glucosamine hydrochloride, 12% DMSO and 2% Marcaine.   These solutes were mixed in a solution of 33% contrast, and 33% dextrose (50% concentration).   It was hoped that the disc solution would stimulate “a reparative response” within the disc and slowly lessen the patients’ pain and functional disability.   Most patients received 2 or 3 of these injections every three months over a one year period (I’m assuming).

It is noteworthy to mention that this procedure was apparently very painful.   The authors noted the following: “All 30 patients experienced varying degrees of post-injection pain.”   This pain was “moderate to severe” and lasted for three full days.   Medication was able to control the pain in most cases; however, 6 patients (20%) required corticosteroid administration (mostly via epidural injection) as a direct result of this procedure.  

EXPERIMENTAL BLUNDERS?

The authors chose to empirically inject the facet joints with the ‘disc solution’ (minus the chondroitin) as well as the target disc(s).   They offered no explanation for this ‘study ruining step’, other than the statement, “…this was not practical in a private practice setting and with a pilot study.”   Apparently they felt that relieving the patient’s pain syndrome was more important than worrying about the construction of a proper investigation.   This is all well and fine, but then why bother to publish such a non-investigatory investigation?   Empiricism (the reliance of practical knowledge rather than science based upon fact), certainly has no place in the investigatory arena in my book! How can one discovery scientific certainty by using methodology based upon empiricism?

Another oddity of this investigation was the fact that the patients were allowed to continue their regular treatment regimes, some of which included epidural steroid injections during the investigation period!   Again, since other forms of treatment were occurring at the same time of this investigation, how do we know for sure that it was the “disc solution” that was responsible for the reported improvement in some of these patients?   We don’t, as the authors openly admit.

RESULTS:

The patients were followed for an average of 13 months, at which time the second round of disability questionnaires were completed. There was no mention of how these tests were administored or if the 13 month average follow-up was calculated following the first injection or following the last injection (some patients had four injections.)

Although the over-all results look amazing, the truth of the study was that there was a real dichotomy within the group.   In other words, some patients responded very well to the ‘disc solution’, while others did not.   More explicitly, 43% of these patients did not adequately respond to the treatment, but 57% of the patients improve at least by 50%.   The average improvement of the latter subgroup was an impressive 74%!   In layman’s terms, you apparently “either get better or you don’t” with this type of treatment.

RESULT TABLE:

DISCUSSION:

The bottom line of this investigation is that if you fit the entry criteria - which seem very broad, except for the need for concordant pain upon discography - you’ve got about a 50/50 chance of having some real improvement, i.e., an average of 74% improvement in pain and disability, although we have no clue as to where your chronic pain was coming from, nor what part of the treatment had this positive effect to upon you.

All patient who responded well to this form of treatment, had “significant improvements” noted after the first injection of “disc solution”; whereas, ‘non-responders (the patients in whom the treatment didn’t help) did NOT respond after that first injection.   Bottom line number 2: if it’s going to work, you will know by the results you obtain after the first injection which typically took about three months to reach maximum effect.

Non-Candidates for Disc Injections:

Based upon the results of this study, the authors made some recommendations about which types of patients should be EXCLUDED from this type of treatment; these were as follows: patients who had previously undergone fusion surgery, patients who had been on long term disability (over one year), patients who had a bilaterally positive Straight Leg Raising Test (under 50 degrees), and patients that were extremely 'sensitive' to touch (hypersensitive to palation).

There is a ‘price’ to pay, however, for trying this form of treatment, for 100% of the patients suffered “moderate to severe” pain following the procedure for a period of approximately three days.   And, a significant percentage (20%) of them need a corticosteroid to help relieve the flare-up of pain that when with the initial treatment.   There was no residual pain reported past two months – no damage done.

I’m a little disappointed with the authors choice of title selection which suggested that this paper was an investigation into discogenic pain; when, in reality it only proved that some cases of longstanding chronic back pain – which were though to be discogenic in nature – could be improved with the addition of intra-discal and facetal injections of a ‘disc solution’ as a supplement to their current treatment regime.

THEORY & OPINION:

“We hypothesize that the reductions in pain and disability seen in this study are the result of favorable alterations in the biochemical milieu (environment) of the intervertebral disc and apophyseal joints, but we have no direct proof that this is the case, and further studies, including serial magnetic resonance imaging scans, are clearly needed to address this important question.”   “…we do not know the potential for relapse, which will require longer follow-up.”

My biggest problem with the whole field of research ‘artificial discal rejuvenation’, is that it doesn’t address the ‘CAUSE’ of the pathological disc degeneration; it only addresses the resultant effects of such degeneration, i.e, anular disruptions within the disc.   Without an adequate supply of discal nutrients, which seems to result from an idiopathic loss of the food-bearing blood vessels within the region of the vertebral end-plate (6), as well as other factors (506, 537,538,552), any attempts to stimulate or repair the substance of the disc will eventually meet the same ‘fate’ that originally killed-off or disabled the disc cells and allowed for discal disruption in the first place. (7)  

A quote from multi Volvo Award Winner Dr. Norbert Boos seems appropriate here:  

“…we elected also to empirically treat the zygapophyseal joints at the affected disc levels.   The contribution of the intervertebral disc and zygapophyseal joints to the total burden of chronic low back pain in individual patients is debatable.” (9 ,5)

Apparently the authors felt that relieving the patient’s pain syndrome was more important than worrying about the construction of a proper investigation.   This is all well and fine, but then why bother to publish such a non-investigatory investigation in the first place?   Empiricism (the reliance of practical knowledge rather than science based fact), certainly has no place in the investigatory arena in my book!

References:

1) Roland MR, Morris RM.   “A study of the natural history of back pain.”   Spine 1983; 8:141-4

2) Huskisson EC. "Measurement of pain." Lancet 1974; 2:1127-31

5) Schwarzer A, Aprill C, Derby R, et al. “The relative contributions of the disc and zygapophyseal joint in chronic low back pain.” Spine 1995; 19:801-6

6)   Boos N, et al. "Classification of Age-Related Changes in Lumbar Intervertebral Discs 2002 Volvo Award in Basic Science" Spine 2002; Volume 27, Number 23, pp 2631-2644

7)  Horner HA, Urban JPG, "Effects of Nutrient Supply on the Viability of Cells from the Nucleus Pulposus of the Intervertebral Disc: 2001 Volvo Award in Basic Science." Spine 2001; 26(23):2543-2549

9) Steven RL, et al. “Biological changes in the annulus fibrosis in patients with low back pain.” Spine 1982; 7(3):223-33

21) Moon SH, Gilbertson LG, Nishida K, et al. Human intervertebral disc cells are genetically modifiable by adenovirus-mediated gene transfer: Implications for the clinical management of intervertebral disc disorders. Spine 2000; 25: 2573-9.

24) Nishida K, Kang JD, Gilbertson LG, et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: An in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine 1999; 24: 2419-25.

25) Nishida K, Kang JD, Suh JK, et al. Adenovirus-mediated gene transfer to nucleus pulposus cells: Implications for the treatment of intervertebral disc degeneration. Spine 1998; 23: 2437-42.

47 ) Wehling P, Schulitz KP, Robbins PD, et al. Transfer of genes to chondrocytic cells of the lumbar spine: Proposal for a treatment strategy of spinal disorders by local gene therapy. Spine 1997; 22: 1092-7.

506) Bernick S, Sailliet R. "Vertebral endplate changes with aging of human vertebrae." Spine 1982; 7:97-102

537) Roberts S, et al. "The cartilage endplate and intervertebral disc in scoliosis: calcification and other sequelae." J Orthopo Res 1993; 11:747-57

538) Roberts S, Urban J, et al. "Transport properties of the human cartilage endplate in relation to its composition and calcification." Spine 1996; 21:415-20

552) Urban MR, Fairbanks JCT, et al. "Electrochemical measurement of transport into scoliotic intervertebral discs in vivo using nitrous oxide as a tracer." Spine 2001; 26:984-90