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Abstract
Study Design
The ingrowth of the nociceptive nerve ending into intervertebral disc was examined using immunohistochemistry and quantified using western blotting.
Objectives
To determine if the nociceptive nerve innervates into the intervertebral discs of internal disc disruption (IDD).
Summary and Literature Review
Nociceptive nerve ending and vessel ingrowth into intervertebral disc is associated with IDD and HNP. Substance P is a neurotransmitter that is found in the nociceptive nerve endings. Immunohistochemistry has con-firmed the presence, and western blot has isolated the target. The localization of novel nociceptive innervation, and a quantitative comparison was made according to the original pathology is of interest.
Materials and Methods
10 specimens of intervertebral disc were collected from IDD during total disc replacement surgery, and another 10 specimens of intervertebral disc from HNP were collected during discectomy. The control samples of intervertebral disc were obtained from 3 adolescent patients with idiopathic scoliosis, and 2 patients with a lumbar bursting fracture. Standard immunohistochemical techniques were used to test for the nociceptive neurotransmitter (substance P), which is a protein expressed during axonogenesis (growth-associated protein 43, GAP43), and a general nerve marker (protein gene produce 9.5, PGP9.5). The expression of substance P protein was quantified using western blot for its polyclonal antibody.
Results
In IDD (n=10), substance P was expressed in 6 cases of outer annulus fibrosus (AF), 5 cases of inner AF, and 3 cases of nucleus pulposus (NP). In HNP (n=10), substance P was expressed in 4 cases of outer AF, 3 cases of inner AF, and 2 cases of NP. In the control group, only 2 cases expressed substance P in outer AF. GAP43 was only positive in outer AF as follows: IDD 3 cases, HNP 1 case, and control 1 case. None of the specimens showed localized PGP 9.5. Substance P was localized significantly in larger quantities in IDD than in the control group (p=0.002). In HNP, the expression level was larger than the control and lower than the IDD group but this was not statistically significant (p=0.158, p=0.108).
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REFERENCES
1). Hirsch C, Ingelmark BE, Miller M. The anatomical basis for low back pain. Studies on the presence of sensory nerve endings in ligamentous, capsular and intervertebral disc structures in the human lumbar spine. Acta Orthop Scand. 1963; 33:1–17.
2). Bogduk N, Windsor M, Inglis A. The innervation of the cervical intervertebral discs. Spine. 1988; 13:2–8.
3). Weinstein J, Claverie W, Gibson S. The pain of discography. Spine. 1988; 13:1344–1348.
4). Weinstein J, Pope M, Schmidt R, Seroussi R. Neu-ropharmacologic effects of vibration on the dorsal root ganglion. An animal model. Spine. 1988; 13:521–525.
5). Stolker RJ, Vervest AC, Groen GJ. The management of chronic spinal pain by blockades: a review. Pain. 1994; 58:1–20.
6). Bleys RL, Groen GJ, Matthijssen MA. A method for identifying peripheral connections of perivascular nerves based on sensitive acetylcholinesterase staining via perfusion. J Histochem Cytochem. 1994; 42:223–230.
7). Groen GJ, Baljet B, Drukker J. Nerves and nerve plexuses of the human vertebral column. J Anat. 1990; 188:282–296.
8). Morinaga T, Takahashi K, Yamagata M, et al. Sensory innervation to the anterior portion of lumbar intervertebral disc. Spine. 1996 Aug 15; 21:1848–1851.
9). Ashton IK, Ashton BA, Gibson SJ, Polak JM, Jaffray DC, Eisenstein SM. Morphological basis for back pain: the demonstration of nerve fibers and neuropeptides in the lumbar facet joint capsule but not in ligamentum flavum. J Orthop Res. 1992; 10:72–78.
10). Pedersen HE, Blunck CF, Gardner E. The anatomy of lumbosacral posterior rami and meningeal branches of spinal nerve (sinu-vertebral nerves); with an experimental study of their functions. J Bone Joint Surg. 1956; 38-A:377–391.
11). Malinsky J. The ontogenetic development of nerve termi-nations in the intervertebral discs of man. (Histology of intervertebral discs, 11th communication). Acta Anat (Basel). 1959; 38:96–113.
12). Jackson HC, Winkelmann RK, Bickel WH. Nerve endings in the human lumbar spinal column and related structures. J Bone Joint Surg. 1966; 48-A:1272–1281.
13). Yoshizawa H, O'Brien JP, Smith WT, Trumper M. The neuropathology of intervertebral discs removed for low-back pain. J Pathol. 1980; 132:95–104.
14). Kaapa E, Gronblad M, Holm S, Liesi P, Murtomaki S, Vanharanta H. Neural elements in the normal and exper-imentally injured porcine intervertebral disk. Eur Spine J. 1994; 3:137–142.
15). Osti OL, Vernon-Roberts B, Fraser RD. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model. Spine. 1990; 15:762–767.
16). Saifuddin A, Braithwaite I, White J, Taylor BA, Ren-ton P. The value of lumbar spine magnetic resonance imaging in the demonstration of anular tears. Spine. 1998; 23:453–457.
17). Vernon-Roberts B, Fazzalari NL, Manthey BA. Pathogenesis of tears of the anulus investigated by multiple-level transaxial analysis of the T12-L1 disc. Spine. 1997; 22:2641–2646.
18). Burke JG, Watson RW, McCormack D, Dowling FE, Walsh MG, Fitzpatrick JM. Intervertebral discs which cause low back pain secrete high levels of proinflammato-ry mediators. J Bone Joint Surg Br. 2002; 84:196–201.
19). Henry JL. Relation of substance P to pain transmission: neurophysiological evidence. Ciba Found Symp. 1982; 91:206–224.
20). Giles LG, Harvey AR. Immunohistochemical demonstration of nociceptors in the capsule and synovial folds of human zygapophyseal joints. Br J Rheumatol. 1987; 26:362–364.
21). Korkala O, Gronblad M, Liesi P, Karaharju E. Immunohistochemical demonstration of nociceptors in the ligamentous structures of the lumbar spine. Spine. 1985; 10:156–157.
22). McCarthy PW, Petts P, Hamilton A. RT97- and calci-tonin gene-related peptide-like immunoreactivity in lumbar intervertebral discs and adjacent tissue from the rat. J Anat. 1992; 180:15–24.
23). Ashton IK, Roberts S, Jaffray DC, Polak JM, Eisenstein SM. Neuropeptides in the human intervertebral disc. J Orthop Res. 1994; 12:186–192.
24). Coppes MH, Marani E, Thomeer RT, Groen GJ. Innervation of "painful" lumbar discs. Spine. 1997; 22:2342–2350.
25). 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; 350:178–181.
26). Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y. The pathogenesis of discogenic low back pain. J Bone Joint Surg Br. 2005 Jan; 87:62–67.
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Figures and Tables%
 | Fig. 1.CT discography shows leakages of dye. Intervertebral disc specimens is obtained from the indicated area by rectangle (A). MRI of the same patient shows the degeneration of intervertebral disc of L4-5, L5-S1 and the hight intensity zone (B) |
 | Fig. 2.Photomicrographs showing evidence of innervation in internal disc disruption. SP-immunoreactive nerve fiber is present in outer one third of the annulus fibrosus (arrows in A and B), and in the nucleus pulposus, with longitudinal (open arrows in C and D) and cross (arrows in E and F) section. (SP: substance P). |
 | Fig. 3.(A, B) GAP43-immunoreactive nerve fiber (arrow) is present in the annulus fibrosus of IDD (A) and of HNP (B). |
 | Fig. 4.Westen blots and statistical analysis. Statistically significantly more expression of substance P in IDD than control group (p IDD-control=0.002) (one-way ANOVA; SPSS 11.0 for windows). |
Table 1.
Patient Information
Table 2.
MR and CT Discographic Findings of IDD (HIZ, High Intensity Zone)
| No.* | Concordant pain | MRI grade† | HIZ† | Decreased disc height | End plate abnormality (Modic type**) | Facet osteoarthritis+ (grade) | Discography++ |
|---|---|---|---|---|---|---|---|
| 1 | + | 5 | - | + | I | 2 | V |
| 2 | + | 5 | + | + | - | 1 | V |
| 3 | + | 4 | - | + | - | 2 | V |
| 4 | + | 5 | + | - | I | 2 | V |
| 5 | + | 4 | + | + | I | 2 | V |
| 6 | + | 5 | + | + | III | 3 | V |
| 7 | + | 5 | + | - | III | 1 | V |
| 8 | + | 5 | + | + | I | 1 | V |
| 9 | + | 3 | - | + | III | 1 | V |
| 10 | + | 5 | - | + | II | 1 | V |
† : grade 3. mild degeneration, blurred differentiation of the nucleus pulposus from the annulus, slightly decreased signal of the nucleus pulposus with minor irregularities; grade 4, moderate disc degeneration, blurred differentiation of the nucleus pulposus from the annulus, moderately decreased signal of the nucleus pulposus, with hypointense zones; grade 5, severe degeneration, a loss of differentiation of the nucleus pulposus from the annulus, hypointense signal of the nucleus pulposus with or without a hori-zontal hyperintense band.
† : focal zone of high signal intensity within the posterior aspect of the annulus fibrosus, without focal protrusion or extrusion of the disc.
∗ : type I, low signal intensity of T1-weighted images and high signal intensity on T2-weighted images; type II, high signal intensity on both images; type III, low signal intensity on both images.
+ : grade 1, mild degenerative disease(indicated by narrowing of the facet joint space, small osteophytes, and/or mild hypertrophy of the articular process); grade 2, moderate degenerative disease(indicated by narrowing of the facet joint space, moderate osteophytes, moderate hypertrophy of the articular process, and/or mild subarticular erosions); grade 3, severe degenerative disease(indicated by narrowing of the facet joint space, severe osteophytes, severe hypertrophy oh the articular process, severe subarticular erosions, and/or subchondral cysts).
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