Abstract
Recent advances in basic research on intervertebral disc have revealed the unique innervation pattern and the pathological changes related to generation of low back pain. In this presentation, we will review the results obtained mainly at author's institution and to discuss the future treatment of discogenic low back pain.
The intervertebral disc has been confirmed as a pain source in early 20th century by stimulation of the annulus fibrosus during posterior spine surgery under local anesthesia.1,2 In 1970, Shinohara3 reported the presence of nerve fibers in the deep layers of the annulus fibrosus of the degenerated disc, which was obtained during anterior decompression and interbody fusion surgery in patients with painful lumbar disc. Groen et al4 studied the anatomy of nerves and nerve plexuses in the human fetus with acetylcholinesterase whole-mount method. Groen reported that the vertebral column is surrounded by ventral and dorsal nerve plexuses which are interconnected. In 1993, Takahashi et al5 demonstrated that the rat L5-L6 disc was innervated by the upper L2 dorsal root ganglion (DRG) neurons. In 1997, Freemont et al6 reported nerve ingrowth into diseased intervertebral disc in patients with chronic back pain. Thereafter, Ohtori et al7 showed that the sensory fibers from T13, L1, and L2 DRGs innervated the dorsal portion of the L5-L6 disc through the paravertebral sympathetic trunks, whereas those from L3-L5 DRGs may innervate the disc through the sinuvertebral nerves in rats. In 2004, Aoki et al8 reported that nerve growth factor (NGF)-sensitive neurons are predominant in the rat intervertebral disc. On the contrary, there are very few glial cell line-derived neurotrophic factor-sensitive neurons in the rat disc, indicating that discogenic pain can be related to inflammatory pain rather than neuropathic pain. In 2009, Yamauchi et al9 cocultured DRG cells from newborn Wistar rats with conditioned medium of nucleus pulposus or annulus fibrosus cells obtained from patients with discogenic low back pain, and the average length of the axons from the DRG neurons was measured. She reported NGF of cultured medium from human degenerative nucleus pulposus promoted sensory nerve growth in vitro. In 2012, Miyagi et al10 reported that disc dynamic compression in rats produces long-lasting increases in inflammatory mediators (NGF, TNF-α, interleukin-1β, interleukin-6) in discs and induces long-lasting nerve injury and regeneration of the afferent fibers innervating discs using rats. Tumor necrosis factor α (TNF-α) has been reported as a pain-related proinflammatory mediator in the degenerative intervertebral disc. Sainoh et al11 reported a prospective randomized study in which bupivacaine 2 mL with etanercept 10 mg was administered intradiscally in 30 patients with discogenic low back pain (etanercept group) and bupivacaine 2 mL was administered into the disc in other 30 patients (control group). Visual analog scale and Oswestry Disability Index were used for evaluation. He reported that intradiscal administration of 10-mg etanercept significantly improved the clinical outcomes of the patients with discogenic low back pain after 4 weeks without any adverse events.
At present, majority of low back pain were classified into nonspecific low back pain. However, to improve our treatment of patients with low back pain, we have to know the exact pathophysiology. We believe the basic and the clinical researches will surely open a new horizon in the treatment of patients with low back pain.
None declared
Spurling RG, Grantham EG. Neurologic picture of herniations of the nucleus pulposus in the lower part of the lumbar region. Arch Surg 1940;40:375-388
Falconer MA, McGEORGE M, Begg AC. Observations on the cause and mechanism of symptom-production in sciatica and low-back pain. J Neurol Neurosurg Psychiatry 1948;11(1):13–26
Shinohara H. A study on lumbar disc lesion. Significance of histology of free nerve endings in lumbar disc. J Jpn Orthop Assoc 1970;44:553-570
Groen GJ, Baljet B, Drukker J. Nerves and nerve plexuses of the human vertebral column. Am J Anat 1990;188(3):282–296
Takahashi Y, Nakajima Y, Sakamoto T, Moriya H, Takahashi K. Capsaicin applied to rat lumbar intervertebral disc causes extravasation in the groin skin: a possible mechanism of referred pain of the intervertebral disc. Neurosci Lett 1993;161(1):1–3
Freemont AJ, Peacock TE, Goupille P, Hoyland JA, O’Brien J, Jayson MI. Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 1997;350(9072):178–181
Ohtori S, Takahashi Y, Takahashi K, et al. Sensory innervation of the dorsal portion of the lumbar intervertebral disc in rats. Spine 1999;24(22):2295–2299
Aoki Y, Ohtori S, Takahashi K, et al. Innervation of the lumbar intervertebral disc by nerve growth factor-dependent neurons related to inflammatory pain. Spine 2004;29(10):1077–1081
Yamauchi K, Inoue G, Koshi T, et al. Nerve growth factor of cultured medium extracted from human degenerative nucleus pulposus promotes sensory nerve growth and induces substance p in vitro. Spine 2009;34(21):2263–2269
Miyagi M, Ishikawa T, Kamoda H, et al. ISSLS prize winner: disc dynamic compression in rats produces long-lasting increases in inflammatory mediators in discs and induces long-lasting nerve injury and regeneration of the afferent fibers innervating discs: a pathomechanism for chronic discogenic low back pain. Spine 2012;37(21):1810–1818
Sainoh T, Orita S, Yamauchi K, et al. Intradiscal administration of tumor necrosis factor-alpha inhibitor, etanercept, clinically improves intractable discogenic low back pain: a prospective randomized study. International Society for the Study of the Lumbar Spine Abstract Proceedings; 40th Annual Meeting; Scottsdale, AZ; May 13-17, 2013