The history of intradiscal injection for Degenerative Disc Disease  is a long one.

For decades we have been injecting the discs: hoping to alight on the right combination of medicines or restoratives to return the fragile degenerative  disc disease to its original physiologic capacity: thick strong and tall.

Over the decades we have injected: papaya, cortisone, alcohol, saline, lidocaine, marcaine, hyaluronic acid, plasma, blood, PRP, methylene blue, dextrose, sealants and mesenchymal stem cells.

The last three have promise.  The previous many have little promise: either being ineffective, or possibly effective but too risky.

Degenerative Disc Disease described by Kevin Pauza, M.D.

An Investigational Biologic Therapy for Discogenic Low Back Pain and 

Degenerative Disc Disease

Author: Kevin Pauza, M.D.

Low back pain is a major health concern and the most common reported pain among the U.S. adult population. Nearly 50 percent of the 220 million adults in the U.S. experience an episode of low back pain each year.

Most low back pain attacks resolve within six to 12 weeks; however, for ten to 15 percent of people, the low back pain becomes chronic (persisting for longer than three months). The annual cost of low back pain in the U.S. has been estimated to range from $16 to $50 billion with annual compensation costs of $4.6 billion. Despite its high prevalence and cost, accurate diagnosis and efficacious treatment of low back pain remains a challenging medical problem.

As the natural history of acute low back pain is favorable, with most patients experiencing spontaneous resolution within a period of weeks to months, identification of the precise structures causing acute low back pain has proven difficult. However, in patients with chronic low back pain, precise structural causes have been defined. Contrary to common perception, nerve root compression or inflammation due to disc herniation does not cause primary chronic axial back pain, but results in extremity pain. Common sources of chronic axial low back pain include pain arising from the synovial joints, syndesmotic joints and the intervertebral discs themselves.

Origins of Discogenic Pain

Internal disc disruption (IDD) is a phrase coined by Crock that is characterized by symptoms of chronic low back pain, with or without nonradicular referred pain, not resulting from fracture, instability, tumor
or infection. (See Exhibit 1.) Crock described marked alteration of the internal structure of the disc with loss of distinction between the nucleus pulposus and the anulus fibrosis and the presence of fissuring of the anulus.
Externally, the disc appears intact and there is no nerve-root compression.

Radiographic changes often associated with degenerative disc disease (DDD), such as disc space narrowing, osteophytes and endplate
sclerosis, are not present in IDD. IDD is described as a pathological process affecting the disc distinct from DDD and segmental instability.

Schwarzer et al. estimated that symptomatic IDD accounted for 39 percent of patients with chronic low back pain. Studies also demonstrate
that anular fissures are not necessarily pathognomonic features of aging discs or of degenerative changes, and that discogenic pain does not necessarily correlate with aging or degenerative changes in and of themselves.
Instead, pain is strongly associated with the presence of anular fissures only, but not all discs demonstrating anular fissures cause pain.
Exhibit 1: Intervertebral disc with internal disc disruptions

A structure must have a nerve supply in order to cause pain. Gross dissections and histological studies confirm that the outer one-third of the anulus fibrosis of both normal and disrupted discs is densely populated
with nociceptive nerve endings, including terminal nerve endings of the sinuvertebral nerve11. Nociceptive fibers also may penetrate the inner anulus of diseased discs. Immunohistochemical studies demonstrate
that these nerves contain peptides such as CGRP, vasoactive intestinal peptide and substance. Nerves that contain these peptides convey the sensation of pain. That the disc has not only innervation, but innervation
specific to generating pain is overwhelmingly supported on the basis of scientific studies. In vivo human studies have also demonstrated that the posterior disc anulus is exquisitely sensitive to mechanical stimulation, resulting in the perception of pain in humans. Thus one mechanism of chronic low back pain involves the stimulation of these nociceptive nerve fibers in the outer posterior disc anulus, either from mechanical stimulation (tears of the anulus or mechanical stress) or from tissue inflammation. Chronic low back pain arising from this mechanism (“symptomatic internal disc disruption,” “symptomatic IDD,” “discogenic
pain”) can be differentiated from disc pain arising from advanced degenerative changes (“disc pain”).

Because nociceptive sensory afferents entering the dorsal horn of the spinal cord become facilitated in the presence of constant stimulation, and because primary afferent sensory neurons entering the dorsal horn branch (or span) multiple segments, pain arising from a specific structure will often result in the perception of pain in other structures anatomically distinct from the cardinal pain source, but sharing overlapping dorsal horn
receptor fields. Thus, pain arising from a symptomatic lumbar disc will often be perceived as involving the buttock, groin or lower extremity in the absence of any pathology involving joints, muscles or the spinal
nerves themselves. This phenomenon is known as somatic referred pain.

Presently, no universally recognized, nonoperative standard of care exists for treatment of discogenic pain. Common conservative treatments may include rest, heat, physical therapy, manual therapies, oral analgesics and lifestyle modification. Until fairly recently, when pain failed to respond to conservative therapies the next step was aggressive surgical intervention (e.g.,fusion), although there is little scientific evidence
to support lumbar fusion for chronic discogenic pain and clinical results have been mixed with a wide range of failure rates reported. More
recently, minimally invasive therapies such as intradiscal corticosteroid injections, intradiscal electrothermal therapies and percutaneous discectomy have been studied, although the clinical efficacy of these approaches is yet to be universally confirmed by well-designed prospective controlled
trials. Even newer experimental open surgical procedures to replace part of the anulus fibrosus or the entire disc nucleus with synthetic polymers are under investigation. Prospective studies evaluating lumbar
disc arthroplasty (disc replacement) have been discouraging, with outcomes no better than fusion.

Impaired Healing in the Disc

The efficient and orderly process of healing is hindered in the intervertebral disc because it has very little blood supply. All soft tissues in the body heal through a series of strongly interrelated and mutually codependent
processes. (See Exhibit 2.) The initial stage of tissue repair is dependent on local vasculature and requires bleeding. Bleeding helps cleanse the wound and supply damaged tissue with regenerative and inflammatory cells. Bleeding continues until components in blood plasma contact the damaged tissues. This interaction stimulates coagulation and formation of an adhesive fibrin clot. The fibrin clot halts bleeding, seals the wound and provides a tissue scaffold to support the remaining cellular tissue repair processes. Cellular repair is initiated by inflammatory
processes that are designed to eliminate damaged tissue debris.

These processes, in turn, release factors that stimulate the formation of blood vessels (angiogenesis) and the proliferation of tissue repair cells.

Blood vessels eventually provide the vascular network necessary to support the repair cells as they fill the defects with granulation tissue. Soft tissue healing concludes as the granulation tissue eventually remodels
into stronger and more highly organized scar tissue.

Exhibit 2: Normal soft tissue repair processes

The lack of a sufficient blood supply in the disc prevents the earliest processes required for soft tissue repair – bleeding and clot formation. As a consequence, limited potential exists for annular disruptions to be filled
with fibrin from the blood stream. The lack of this essential scaffold can hinder the remaining cellular dependant repair processes and leave the disc in a state of chronic inflammation.

Potential Benefits of Fibrin Sealant in the Treatment of Discogenic Pain

Fibrin sealant is a biologic agent derived from human plasma derivatives, primarily fibrinogen and thrombin, which when combined, mimic
the last step of the coagulation cascade to form an insoluble fibrin clot.

Fibrin sealants have a long history of research and have been studied in a variety of clinical applications, including control of bleeding (hemostatic agent), sealing of tissue planes, gluing tissues together and drug delivery. In their review, Kjaergard and Fairbrother reported more than 2,300 clinical papers have been published on the surgical applications of fibrin sealant with the largest number in the area of cardiothoracic surgery. Fibrin sealant has application throughout many surgical
disciplines, including orthopaedic and neurosurgery. In the U.S., fibrin sealant is indicated as an adjunct for hemostasis in several clinical applications in situations where conventional surgical techniques, including suture, ligature and cautery, prove ineffective or impractical.

Data from a small IRB-approved study suggests that intradiscal application of fibrin sealant should be investigated as an alternative for
treating discogenic back pain associated with IDD in the lumbar spine.

During the study, eleven patients were treated utilizing a commercially available fibrin sealant and delivery mechanism. After six months 73 percent of the patients had achieved a 20mm decrease in their VAS score and
55 percent of the patients had achieved at least a 50 percent reduction in their VAS score compared to baseline. This early clinical experience also revealed the need for an improved application mechanism which would
allow more controlled delivery of the fibrin sealant.

Various methods and delivery devices have been developed for applying fibrin sealant in surgical applications. It is possible to sequentially apply the two main components (fibrinogen and thrombin) of fibrin
sealant, but most delivery devices are based on simultaneous application of the two components through paired syringes or sprays. Mixing of
the fibrinogen and thrombin is essential to ensure consistency in the mechanical properties of the clots. Commercial fibrin sealants have concentrations of fibrinogen and thrombin that are significantly higher than those found in blood. As a result, the fibrin matrix forms rapidly and clotting within the delivery mechanism can become problematic.

Experimental and pilot use of existing devices highlighted the need for a new delivery system which can delay solidification of the fibrin matrix until the materials have entered the disc while still providing optimum mixing of fibrinogen and thrombin to warrant homogeneous strength properties within the resulting matrix. The new device should also allow
the clinician to know precisely how much fibrin sealant has been introduced into the disc while simultaneously providing pressure readings to
prevent accidental overpressurization of the disc. These delivery mechanism improvements would make intradiscal application of fibrin sealant more feasible within a clinical setting in the future.

Although the actual mechanism(s) of pain relief upon application of fibrin into the disc have not been completely established, it is postulated that fibrin may effect a biological change in several ways. Application of fibrin sealant may act to fill voids, thereby precluding occupation of the voids by inflammatory chemicals, seal tears and fissures, disrupt the inflammatory cascade caused by the leaking nucleus pulposus, alter the biologic milieu of the disc and inhibit the formation or facilitate the removal of free protons (known to facilitate permeability of ligand-gated ion channels). In addition, fibrin sealant forms a temporary three-dimensional
matrix, thus providing the necessary framework upon which fibroblasts and other reparative cells can bind and potentially restore tissue.
Over time, as the fibrin matrix itself degrades, its degradative components
may serve as chemotactic agents, stimulating reparative cellular accretion necessary for disc tissue restoration.

Conclusion

Discogenic low back pain continues to be a challenge for physicians attempting to help patients with their pain. While the theoretical benefits of intradiscal application of fibrin sealant are intriguing, the safety and efficacy
of this treatment must be proven before implementing it in the clinical setting. This is especially essential in a current climate of spine care where the clinical efficacy of intradiscal therapies and surgical intervention alike are under increased scrutiny. An Investigational Device Exemption clinical
trail of the Biostat™ Disc Augmentation System (Spinal Restoration, Inc.),
a distinctively formulated fibrin sealant and a delivery system designed specifically for this application, is expected to begin in 2008.

Dextrose:

Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose.

Several promising techniques as surfacing in the literature and in prospective studies.

Percutaneous augmentation annuloplasty using a biologic fibrin and thrombin gel for disc repair is perhaps the most exciting work yet.

Biostat is the drug name being studied.

Intradiscal dextrose has prospective litterature in its support.

Intradiscal ethanol in gel suspension.

intradiscal stemcell or mesenchymal stemcell injection.