Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats

doi:10.1016/S1566-0702(00)00194-6

Autonomic Neuroscience

Volume 86, Issues 1–2, 28 December 2000, Pages 13-17

https://doi.org/10.1016/S1566-0702(00)00194-6 Get rights and content

Abstract

The rat L5/6 facet joint is innervated from L1 to L5 dorsal root ganglions (DRGs) multisegmentally. Sensory fibers from L1 and L2 DRGs were reported to innervate nonsegmentally through the paravertebral sympathetic trunks, while those from L3 to L5 DRGs segmentally innervate the L5/6 facet joint. The presence of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive (ir) nerve fibers has been demonstrated in the lumber facet joints, but their ratios have not been determined. Fluoro-gold (F-G) labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs for levels L1 to L5. Of the F-G labeled neurons, the ratios of SP-ir L1, L2, L3, L4 and L5 DRG neurons were 13, 15, 29, 31 and 30%, respectively, and those of CGRP-ir neurons were 17, 24, 44, 56 and 50%, respectively. The ratios of SP and CGRP-ir neurons in L1 and L2 DRGs were significantly less than those in L3, L4 or L5 DRGs. In conclusion, the neurons of L3, L4 and L5 DRGs may have a more significant role in pain sensation of the facets than L1 and L2 DRG neurons.

Introduction

Many studies have reported the lumbar facet joints as a possible source of low back pain (Eisenstein and Parry, 1987, Fairbank et al., 1981, Lippitt, 1984; Mooney and Robertson, 1976, Shealy, 1976, Yamashita et al., 1990). Morphologically, the joint capsule is well innervated, receiving a nerve supply from the medial branches of the dorsal rami. Each medial branch segmentally innervates at least two or three facet joints. For example, the human L4/5 facet joint is innervated by the medial branches of the dorsal rami from L3 and L4 spinal nerves (Bogduk and Long, 1979, Bogduk, 1983, Cavanaugh et al., 1989, Edgar and Ghadially, 1976, Pedersen et al., 1956).

Sensory innervation of the lumbar facet joint is thought to be segmental. However, patients with lower lumbar facet lesions sometimes experience diffuse low back pain, anterior thigh or inguinal pain. The anterior thigh and inguinal regions are in the L1 or L2 dermatomes, which do not correspond to segmental innervation of the facet joints (Takahashi et al., 1994, Takahashi et al., 1995).

Recently, it was reported that the ventral portion of the L5/6 disc is innervated only by the L1 and L2 DRGs in rats (Morinaga et al., 1996), and that the dorsal portion of the L5/6 disc is multi-segmentally innervated by T13 to L2 DRGs through sinuvertebral nerves via paravertebral sympathetic trunks and by L3 to L6 DRGs directly through sinuvertebral nerves on the posterior longitudinal ligament (Ohtori et al., 1999). Some sensory fibers only travel in the sympathetic chain, but have no direct relation to sympathetic neurons. On the other hand, the L5/6 facet joint is reported to be innervated by DRGs multi-segmentally from L1 to L5 levels, and nerve fibers from L1 and L2 DRGs pass through the paravertebral sympathetic trunks (Suseki et al., 1996, Suseki et al., 1997). However, there are two types of neurons in the DRGs, which are related to pain and to position sense, respectively.

Substance P (SP) and calcitonin gene-related peptide (CGRP) are sensory markers related to pain (Hökfelt et al., 1975; Lee et al., 1985, Miletic and Tan, 1988; Otsuka and Yanagisawa, 1987, Pernow, 1983, Silverman and Kruger, 1989). It has been reported that SP and CGRP immunoreactive (ir) nerve fibers are present within the lumbar facet joint capsules (Ashton et al., 1992, Beaman et al., 1993, El-Bohy et al., 1988, Grönblad et al., 1991), but the ratios of SP and CGRP-ir DRG neurons innervating the lumbar facet joints remain to be determined. The present study was undertaken to measure the ratios of SP and CGRP-ir DRG neurons at each segmental level innervating the L5/6 facet joint using the retrograde neurotransport method and immunohistochemistry. The L1 and L2 DRG neurons innervating the L5/6 facet joint through sympathetic trunks and the L3, L4 and L5 DRG neurons innervating the L5/6 facet joint via other routes, i.e. not through sympathetic trunks, are discussed separately.

Section snippets

Materials and methods

Twenty male Sprague-Dawley (SD) rats weighing 250–300 g were used. The studies described were authorized by the appropriate local Ethics or other Animal Experimentation Committee of Chiba University. The rats were anesthetized with sodium pentobarbital (40 mg/kg, i.p.) and treated aseptically throughout the experiments. A midline dorsal longitudinal incision was made over the lumbar spine. The left L5/6 facet joint capsule was exposed under a microscope. A 26-gauge needle, the tip of which was

F-G labeled DRG neurons

In F-G labeled DRG neurons transported from the facet joint, labeled neurons were present in the left DRGs from L1 through L5 (Table 1, Table 2). No labeled neurons were observed in the bilateral T13 or L6 DRGs and in the contralateral DRGs from L1 through L5. Of the F-G labeled neurons, 63% were recognized in the L3, L4 and L5 DRGs, and the remaining 37% in the L1 and L2 DRGs. The L1 and L2 DRG neurons related to sympathetic trunks and the L3, L4 and L5 DRG neurons are discussed separately.

Discussion

Many investigators have reported that the lumbar facet joint is innervated by the dorsal ramus of spinal nerves consisting of segmental spinal sensory fibers and postganglionic sympathetic fibers (Bogduk and Long, 1979, Bogduk, 1983, Cavanaugh et al., 1989, Edgar and Ghadially, 1976, Pedersen et al., 1956).

Suseki et al., 1996, Suseki et al., 1997 also reported that the rat L5/6 facet joint is innervated by DRGs from L1 to L5 levels based on a study using the cholera toxin B subunit (CTB). They

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Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats

Abstract

Introduction

Section snippets

Materials and methods

F-G labeled DRG neurons

Discussion

Brain Res.

Neuron

Neuroscience

Brain Res.

Brain Res.

Neurosci. Lett.

Neurosci. Lett.

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.

Substance P innervation of lumbar spine facet joints

Spine

The anatomy of the so-called ‘articular nerves’ and their relationship to facet denervation in the treatment of low back pain

J. Neurosurg.

The innervation of the lumbar spine

Spine

Sensory innervation of soft tissues of the lumbar spine in the rat

J. Orthop. Res.

Innervation of the lumbar spine

Clin. Orthop.

The lumbar facet arthrosis syndrome. Clinical presentation and articular surface changes

J. Bone Jt. Surg. [Br]

Apophyseal injection of local anesthetic as a diagnostic aid in primary low-back pain syndromes

Spine

Silver impregnation and immunohistochemical study of nerves in lumbar facet joint plical tissue

Spine