I. Introduction

In the human lumbar intervertebral disc, many studies have described the existence of sensory nerve endings in the annulus fibrosus ^[1]. It has been believed that such nerve endings originate from the sinuvertebral nerves branching from the ventral ramus of the spinal nerve and the ramus communicans of the corresponding level in human ^[1]. Recent studies have revealed that the dorsal portion of the L5/6 intervertebral disc is multi-segmentally innervated by dorsal root ganglia (DRGs) from T13 to L6 levels in rats ^[2,3]. Some rat sensory nerve fibers from the L5/6 intervertebral disc pass to upper DRGs via paravertebral sympathetic trunks ^[2,3]. However, in humans the sensory afferent pathway from the lower intervertebral disc has not been clarified. Nakamura et al. performed an L2 spinal nerve block based on animal sensory innervation and reported that the block was effective to patients suffering from discogenic low back pain ^[4]. However, they did not compare this with nerve blocks at different levels. The aim of this study was to evaluate and compare the effect of both upper and lower spinal nerve blocks on L4/5 or L5/S1 discogenic pain in humans, and to suggest the sensory pathway from the L4/5 intervertebral disc to the DRGs.

II. Methods

The protocols for human procedures in these experiments received approval from the ethics committees of our institutions.

2. 1 Patients.

We studied 68 patients (43 male and 25 female) whose average age was 36±4 years (Mean±S.E.M.) (range 14〜61 years). Details are shown in Table 1. They all suffered from low back pain. In eleven patients this also involved leg pain. Discogenic pain was diagnosed using physiological examination, pain location, radiography, and magnetic resonance imaging (MRI). We examined patients whose low back pain was exacerbated by forward bending of the trunk as described by Nakamura et al. ^[4]. We also examined patients whose only indication was L4/5, L5/S1, or both intervertebral discs degeneration on MRI imaging. Patients who had severe spinal spodylolysis, or disc degeneration with three or multi-level lesions were excluded. Patients who had received spinal surgery were also excluded.

2. 2 Spinal nerve block.

Administration was as described in a previous report ^[4]. On the predominantly painful side, a 22-guage spinal-nerve-block needle was advanced obliquely to the corresponding spinal nerve under fluoroscopic control (L2 spinal nerve block group, n=34; L4 or L5 spinal nerve block group, n=34). In L4 or L5 spinal nerve block group, L4 or L5 spinal nerve block was applied to only L4/5 disc degeneration, and L5 spinal nerve block was applied to only L5/S1 disc degeneration. If the patients had two disc degeneration (L4/5 and L5/S1), L4 spinal nerve block was applied to the patients. Then 0.5 ml of the contrast medium Iotorolan (Schering AG, Berlin, Germany) was injected to confirm the position of the spinal nerve. Unilateral lidocaine administration (1.5 ml of 1% solution) was then performed. The intensity of low back pain was evaluated before the block using a visual analogue scale (VAS; score, 0〜10: a score of 10 being the worst pain). At 15 minutes, 7 days, 14 days, and 21days after spinal nerve block, the VAS scores were also examined. We defined periods during which patients indicated less than 60% of their VAS score before nerve block as effective periods. The differences between the groups were compared by one-way analysis of variance (ANOVA) for repeated measurements. Differences were considered to be statistically significant at P<0.05.

III. Results

VAS scores before blocks ranged from 7.2 to 10 (8.0±1.2; Mean±S.E.M) in the L2 spinal nerve block group, and from 6.8 to 10 (7.8±1.4; Mean±S.E.M) in the L4 or L5 spinal nerve block group. In both groups, spinal nerve blocks were significantly effective in attenuating discogenic low back pain at 15 minutes, and 7, 14, and 21 days after block (P<0.05) ^{(Table. 2)}. One patient in the L2 nerve block group and one patient in the L4 or L5 spinal nerve block group were not alleviated of low back pain after the nerve block. Average VAS scores were 4.3±1.3 (15 minutes), 3.9±0.8 (7 days), 4.0±1.0 (14 days), and 4.4±1.3 (21 days) in the L2 spinal nerve block group and 3.4±0.8 (15 minutes), 4.3±0.9 (7 days), 6.1±1.2 (14 days), and 6.4±1.2 (21 days) in the L4 or L5 spinal nerve block group. There was no significant difference between the groups at 15 minutes after the blocks (P>0.1). The average VAS score was lower at 14 and 21 days in the L2 spinal nerve block group than in the L4 or L5 spinal nerve block group (P<0.05). VAS scores in the L2 spinal nerve block group for L4/5, L5/S1, or L4/5 and L5/S1 disc degeneration were not significantly different from each levels (P>0.05) ^{(Table. 2)}. VAS scores in L4 spinal nerve block for L4/5, L5/S1, or L4/5 and L5/S1 disc degeneration were not significantly different from those in L5 spinal nerve block for each level (P>0.05) ^{(Table. 2)}. The average effective period was significantly longer in the L2 root block group (13 days) than in the L4 or L5 root block group (8 days) (P<0.05).

IV. Discussion

Discogenic low back pain

In the current study, discogenic pain was diagnosed using pain location, physiological examination and MRI. It is generally difficult to prove the origin of low back pain. However, we defined low back pain as originating from intervertebral discs using the forward bending trunk test ^[4]. MRI findings that excluded the other diagnosis of low back pain substantiated our method. The defined pain was alleviated by spinal nerve block at several different levels.

Intervertebral discs have long been thought to be the main source of the common form of low back pain ^[5]. Many findings regarding discogenic pain in humans and animals have been reported.

Low back pain has been produced by intra-operative stimulation of the outer annulus or the posterior longitudinal ligament under local anesthesia in human ^[6]. Discography induces low back pain in human ^[7]. Many studies have demonstrated nerve endings in the annulus fibrosus in the intervertebral disc ^[1]. Recently, many investigators have identified nerve fibers, immunoreactive for the putative nociceptive markers substance P or calcitonin gene-related peptide (CGRP), in intervertebral discs and DRG neurons innervating intervertebral discs ^[8,9].

Low back pain is usually increased in sustained sitting positions, especially involving forward bending of the trunk, both of which are known to increase intradiscal pressure ^[10]. We assume that the forward bending trunk test, which was used in this study, increases the intradiscal pressure and distends the outer layer of the annulus. As a consequence some sensory nerves in the annulus are stimulated.

Effect of spinal nerve block at different levels on discogenic pain

In rats, sensory nerve fibers from the L5/6 intervertebral disc were thought to pass through the sinuvertebral nerves on the posterior longitudinal ligament and reach the DRGs from L3 to L6. In the non-segmental innervation, sensory nerve fibers were thought to enter the paravertebral sympathetic trunks through the L5 ramus communicans and reach the DRGs from T13 to L2 directly through each ramus communicans ^[2,3,11,12]. In humans, the sensory afferent pathways remain unclear. However, some data have suggested the same pattern of sensory nerve innervation. In the case of lumbar intervertebral disc degeneration, blockade of the spinal nerves at the same level has been effective for some patients with discogenic disorders, but for other patients blockade of L2 spinal nerves or paravertebral sympathetic trunks is effective ^[4,13,14]. In the current study, we did not perform spinal nerve blocks at all levels. However, at least sensory nerves originating from L2, L4, and L5 appear to innervate the human L4/5 or L5/S1 intervertebral disc. In humans, some DRGs at different levels seem to innervate the L4/5 or L5/S1 intervertebral disc. We believe that the sensory pathway from the upper DRG to the disc is via paravertebral sympathetic trunks.

The difference in the effective period of nerve block between the L2, L4, and L5 nerves may be rationalized by the following reports. The number of L2 DRGs innervating the rat L5/6 intervertebral disc is more than that of L4 or L5 DRG ^[2,3]. In addition to the intervertebral disc, lumbar muscles and lumbar facet joints also received sensory nerve fibers from L1 or L2 DRGs via paravertebral sympathetic trunks ^[15-17]. Some sympathetic neurons innervating the lumbar facet joint connect with CGRP-immunoreactive sensory fibers through synaptic contact in paravertebral sympathetic trunks ^[16]. This would allow the transmission of sensory information to sympathetic postganglionic neurons innervating lower lumbar facet joints. Sympathetic postganglionic fibers in the paravertebral sympathetic tract can exert an influence on the activities of the dorsal horn sensory neurons receiving nociceptive stimuli from lumbar paraspinal tissues ^[15] and some sympathetic postganglionic fibers regulate the metabolism of vertebral bone and connective tissues ^[16]. They also may be related to sensory activity in lower lumbar facet joints. If the nervous connection between sympathetic postganglionic neuron innervation in the human intervertebral disc and CGRP-immunoreactive sensory fibers is the same, this would be consistent with the difference in the effective period after L2, L4, and L5 spinal nerve block.

Limitation of this study

1) We defined low back pain as originating from intervertebral discs using the forward bending trunk test and MRI findings. Discography was necessary for diagnosis of discogenic low back pain.

2) Unilateral 1.5 ml of lidocaine administration was performed for L4 or L5 nerve root block group, and the nerve block was effective. We can not deny leakage of lidocaine into intervertebral disc in L4 or L5 nerve root block group.

We need further study to clarify these points.