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The Study | Results | Discussion | Bottom Line

Freemont AJ, et al. "Nerve in-growth into the diseased intervertebral disc (DDD) in chronic back pain. Lancet, 1997;350:178-81

The goal of this study was to see if there was a relationship between 'nerve in-growth', degenerative disc disease, and chronic back pain. 


It is understood that chronic lower back pain is often a complicated and multifaceted phenomenon that disables thousands of people each year. Finding the source of ones back pain is often very difficult. Disc herniations that compress the posterior neural elements (PLL, Dura, Nerve roots, DRG, and Spinal nerve), stenosis, spondylolisthesis, facet syndrome and IDD are commonly treated and researched pain generators but there is mounting evidence that a the diseased disc (DDD) may be generating pain from deep within its own tissue! For years its been taught that the nucleus, inner and central anulus are completely avascular and aneural; meaning that these regions are incapable of generating pain. There is now mounting evidence that pain carrying nerve fiber (which normally is only present in the very outer layers of the disc (701-705)) is growing inward, deep into the middle anulus and even nucleus in some cases! These nerve fibers have now been liked with chronic discogenic pain and must be considered when making a diagnosis.

The goal of this study was to see if there was a relationship between 'nerve in-growth, DDD, and chronic back pain. 

The Study:

46 intervertebral disc samples were obtained from patients undergoing fusion as the result of chronic discogenic back pain. Provocative discography was done on each disc before surgery. There were 30 discs that were found painful and 16 that were tested as non-painful. To act as a control, 34 samples of normal human discs were obtained within 8 hours of death of random people. These controls had no history of past back pain and normal looking discal tissue on macro and microscopic examination.

All discs were then stained and studied microscopically to see if, and how far, nerve fibers had grown into the anulus (which were divided into an inner, middle, and outer 1/3). "Deep nerve growth" was defined as growth into the inner 1/3 of the anulus or farther.


Nerve ingrowth into disc:

No ingrowth

Into outer 1/3 or beyond

Into middle 1/3 or beyond

Into inner 1/3 or nucleus






DDD discs & disco positive: (total number of discs: 30)





DDD discs & disco negative: (total number of discs: 16)





Non-Lower back pain discs: (total number of discs: 34)






It is very interesting to note that 30% of the discogram positive discs were seen to have 'nerve fiber ingrowth' all the way into the nucleus; furthermore, these nerve fibers were NOT traveling with blood vessels, which often accompanied neural ingrowth into the middle anulus (hence can't be vasoregulatory); microscopically looked like pain nerve fiber (nociceptive non-myelinated); and expressed substance P exclusively. (Substance P is a nociceptive pain mediator that signals the nerve to fire off pain signals to the brain.) Even more amazing was the fact that ONLY the discogram positive (+ provocation) discs demonstrated these rogue nerve fibers. These findings "strongly implicate these fibrils in the pathogenesis of chronic low back pain."

"Our findings show that there is an association between ingrowth of nerves expressing substance P and discal degeneration, and that neoneuralisation is greatest at intervertebral disc levels at which the patient experiences pain."

"So what is the biological purpose of nerve ingrowth into intervertebral discs? By analogy with other connective tissues, nerve ingrowth into damaged intervertebral discs could mediate various tissue events, notably healing (228). Initially, an immobilizing nociceptive component to nerve ingrowth might be beneficial, but because the healing process is thought to be poor in this tissue, (229) unproductive nerve ingrowth and pain may result."

"We have shown an association between the frequency and site of back pain and nerve ingrowth into the intervertebral disc, or more specifically the nucleus pulposus. Nerve growth may be part of the process of disturbed repair, and is therefore of little value." "Inhibition of growth of nerve fibers into the intervertebral disc or interference with nociception mediated by these nerves could benefit patients with chronic low back pain."

Bottom Line:

This was the first human experiment that found a direct link between deep nerve ingrowth and the discogenic pain of DDD. Normally the anulus is innervated (has nerve fiber) but the bulk of the innervation occurs in the loose perianular tissue (areolar tissue) that covers the final anular lamella (700). 77% of patients who had undergone a fusion for chronic discogenic back pain, and who had concordant pain on provocative discography, had nerve in-growth all the way into the middle 1/3 of the anulus; versus only 6% of the normal 'control' discs. Even more amazing was fact that 30% of that same fusion group had even deeper nerve ingrowth all the way into the center of the disc (nucleus), that was associated with substance P expression (which is involved in the pain signal process).

There is no doubt in my mind that in the DDD affected discs of some patients, nerve fiber ingrowth, which seems to come from the end-plates, may well be involved in the generation of chronic discogenic pain. This may be yet another strike again treatments such as the IDET, which would not address this source of pain generation.


228) Gronblad M, et al. "Immunoreactive neuropeptides in nerves in ligamentous tissue. Clin Orthop 1991;265:291-96

229) Hirsch C, Schajowicz F, "Studies on structural changes in the lumbar annulus fibrosus." Acta Orthop Scand 1953; 22:184-231

700) Fagan A, Moore R, Vernon Roberts B, et al. "ISSLS Prize Winner: The Innervation of the Intervertebral Disc: A Quantitative Analysis." Spine 2003;28(23): 2570-2576

701) Hirsch C, et al. "The anatomic basis for low back pain." Acta Orthrop 1963;33:11-7

702) Jackson HC, et al. "Nerve endings in the human lumbar spinal column and related structures." J Bone Joint Surg Am 1966;48A:1272-81

703) Kojima Y, et al. "nerve supply to the PLL and the intervertebral disc of the rat vertebral column:" J Anat 1990:169:247-55

704) Ahmed M, et al. Neuropeptide Y, tyrosine hydrooxylase and vasoactive intestinal polypeptide-immunoreactive nerve fibers in the vertebral bodies, discs, dura mater, and spinal ligaments of the rat lumbar spine." Spine 1993;18:268-73

705) Cavanaugh JM, et al. "Innervation of the rabbit lumbar intervertebral disc and posterior longitudinal ligament." Spine 1995;20:2080-5


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