Recovery of the blood flow around the femoral head during early corticosteroid therapy: dynamic magnetic resonance imaging in systemic lupus erythematosus patients.

Disturbance of blood supply to the femoral head is a risk factor for corticosteroid-associated osteonecrosis. The aim was to measure blood supply of the proximal femur during corticosteroid therapy in systemic lupus erythematosus (SLE) patients. We repeatedly performed 78 dynamic MRIs of 19 hip joints in 19 SLE patients after initiation of corticosteroid administration for one year. Blood supply of the femoral head (epiphysis, growth plate, and metaphysis), the femoral neck, and the medial circumflex femoral artery were measured in terms of peak percent enhancement. At the first month, blood supply of the growth plate was significantly higher in the pediatric group (<15 years old) than in the adolescent and adult group (>15 years old). At the fourth month, blood supply in every part of the femoral head (epiphysis, growth plate, and metaphysis) was significantly higher in the pediatric group than in the adolescent and adult group. Multiple regression analysis revealed that blood supply to the femoral head depended on the number of days after initiation of corticosteroid administration and the age at the time of dynamic MRI. Blood supply to the femoral head is abundant in pediatric patients and is a function of the number of days after initiation of corticosteroid administration.

Development of new osteonecrosis in systemic lupus erythematosus patients in association with long-term corticosteroid therapy after disease recurrence.

OBJECTIVES: Systemic lupus erythematosus (SLE) patients are at high risk of developing osteonecrosis, as they require corticosteroid therapy for life. The purpose of this study was to use periodic MRI analysis to clarify (1) the incidence of new osteonecrosis associated with long-term corticosteroid therapy in SLE patients, and (2) the risk factors for delayed osteonecrosis in SLE patients. METHODS: We prospectively studied 291 joints (134 hips and 157 knees) in 106 SLE patients without osteonecrosis after initial corticosteroid therapy, with a mean follow-up period of 13.6 years and a follow-up rate of 71%. All patients had undergone periodic MRI examination of the hip and knee joints for >10 years. RESULTS: New osteonecrosis developed in 6 joints (3%) and only occurred after SLE recurrence in association with increased corticosteroid doses (to>30 mg/day [p=0.008]). New lesions were delayed for a mean 5.9 years after initial corticosteroid administration. The mean time from SLE recurrence to appearance of new lesions was 6.2 months. SLE recurrence occurred in 131 joints (45%), while SLE was well controlled in 160 joints (55%). CONCLUSIONS: We suggest that with respect to long-term effects, total cumulative dose and duration of corticosteroid therapy do not contribute to osteonecrosis. However, SLE recurrence is a risk factor for new osteonecrosis. We recommend MRI screening for osteonecrosis at SLE recurrence.

The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study.

OBJECTIVES: To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. METHODS: Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. RESULTS: Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 sd 1.7, T: mean 4.5 sd 0.5, p = 0.14; eight weeks, S: mean 5.8 sd 0.8, T: mean 4.8 sd 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 sd 1.2, T: mean 4.8 sd 0.4, p = 0.43; eight weeks, S: mean 5.3 sd 0.8,T: mean 5.5 sd 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 sd 9.0N and 13.1 sd 5.6N) or eight weeks (12.6 sd 3.6N and 17.1 sd 6.4N, respectively). CONCLUSION: Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods.Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327-335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2.

Diffusion tensor imaging of radiculopathy in patients with lumbar disc herniation: preliminary results.

AIMS: The aim of this study was to evaluate the time course of changes in parameters of diffusion tensor imaging (DTI) such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in patients with symptomatic lumbar disc herniation. We also investigated the correlation between the severity of neurological symptoms and these parameters. PATIENTS AND METHODS: A total of 13 patients with unilateral radiculopathy due to herniation of a lumbar disc were investigated with DTI on a 1.5T MR scanner and underwent micro discectomy. There were nine men and four women, with a median age of 55.5 years (19 to 79). The changes in the mean FA and ADC values and the correlation between these changes and the severity of the neurological symptoms were investigated before and at six months after surgery. RESULTS: The mean FA values were significantly lower (p = 0.0005) and mean ADC values were significantly higher (p = 0.0115) in compressed nerves than in intact nerves. Although the FA values increased significantly at six months after surgical treatment (p = 0.020), the ADC values decreased but not significantly (p = 0.498). There were strong correlations between the DTI parameters such as the FA value and the severity of the neurological symptoms as assessed using the Japanese Orthopaedic Association (JOA) score and the Roland-Morris Disability Questionnaire (RDQ). CONCLUSION: This preliminary study suggests that it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with lumbar nerve entrapment. TAKE HOME MESSAGE: DTI is a potential tool for functional diagnosis of lumbar nerve damage.

Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn.

Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin. It has been suggested that members of this family control diverse processes in growth, development and the cell cycle.Here, we demonstrate that the DAN protein is produced in the small neurons of the dorsal root ganglion and is transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to the DAN protein suppressed inflammatory pain caused by the introduction of complete Freund's adjuvant or carrageenan into the rat hindpaw. The amount of mRNA for DAN in dorsal root ganglion neurons and of its expressed protein in the spinal dorsal horn were both increased in inflammatory models.Together, these data suggest that the DAN protein may be a novel neuromodulator in primary nociceptive nerve fibers.

Neonatal capsaicin treatment decreased substance P receptor immunoreactivity in lamina III neurons of the dorsal horn.

Using immunohistochemistry and in situ hybridization technique, the distribution of substance P (SP) and SP receptors was studied in the dorsal horn of the rat spinal cord after neonatal capsaicin treatment. Sprague-Dawley rats administered 100 mg/kg of capsaicin subcutaneously within 24 h after birth were examined at 8 weeks of age. In the capsaicin administered rats, slight reduction of SP immunoreactivities in lamina I, and severe decrease in lamina II were observed. In the control group, SP receptor-mRNA was observed in all laminae, and SP receptor-immunoreactivities were seen to be intense in laminae I and III. In contrast, in the capsaicin administered rats, the SP receptor-mRNA expression was low in laminae II-V, and SP receptor immunoreactivities decreased in laminae III-V. Furthermore, the density of the SP receptor immunoreactivities was considerably decreased in the nerve cells of lamina III. We concluded that elevation of the threshold to painful stimulation in rats was as a result of the decrease in SP immunoreactive afferent fibers in laminae I and II, decrease of the SP receptor-mRNA in the laminae II-V, or the decrease in SP receptor immunoreactive neurons in laminae III-V.

Effects of pre-emptively administered nociceptin on the development of thermal hyperalgesia induced by two models of experimental mononeuropathy in the rat.

Pre-emptive analgesia is thought to be produced by the prevention of spinal facilitation evoked by nociceptive input to the spinal cord. Opioid receptor-like 1 (ORL1) receptor agonist has been reported to inhibit the development of spinal facilitation. We investigated the effect of nociceptin, an ORL1 receptor agonist, on the development of thermal hyperalgesia and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn induced by two neuropathic pain models, the chronic constriction injury model and the partial sciatic nerve injury model. Chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. Partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 10 min before the nerve injury. The anti-hyperalgesic effect of drugs was evaluated by the measurement of the paw withdrawal latency (PWL) against thermal nociceptive stimulation. The PWLs of the injured paws were measured 7, 14 and 21 days after the nerve injury. Expression of Fos-LI was examined 2 h after the nerve injury. Intrathecal injection of nociceptin significantly delayed the development of thermal hyperalgesia and decreased the expression of Fos-LI induced by chronic constriction injury, but not that induced by partial sciatic nerve injury. These data indicate that pre-emptive administration of nociceptin might be one strategy for the prevention of the development of neuropathic pain.

Inhibitory effect of intrathecally administered nociceptin on the expression of Fos-like immunoreactivity in the rat formalin test.

Nociceptin, an opioid receptor-like 1 receptor agonist, has been reported to produce an analgesic effect in the rat formalin test. The authors examined the effect of 17 nmol of nociceptin on the expression of Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn induced by paw formalin injection and compared the effect of 17 nmol of nociceptin with that of equiantinociceptive dose (3 nmol) of morphine. Nociceptin and morphine were administered intrathecally 10 min before the formalin injection and the expression of Fos-LI was examined 2.5 h after the formalin injection. Both 17 nmol of nociceptin and 3 nmol of morphine suppressed the expression of Fos-LI in laminae I-II, but not in laminae III-V, to the same extent. These data suggest that intratheally administered nociceptin and morphine suppress the nociceptive input into the laminae I-II and produce antinociceptive effect.

Shock wave application to rat skin induces degeneration and reinnervation of sensory nerve fibres.

There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed whether it produces morphologic changes in cutaneous nerve fibres. In normal rat skin, the epidermis is heavily innervated by nerve fibres immunoreactive for protein gene product (PGP) 9.5 and by some fibres immunoreactive for calcitonin gene-related peptide (CGRP). There was nearly complete degeneration of epidermal nerve fibres in the shock wave-treated skin, as indicated by the loss of immunoreactivity for PGP 9.5 or CGRP. Reinnervation of the epidermis occurred 2 weeks after treatment. These data show that relief of pain after shock wave application to the skin results from rapid degeneration of the intracutaneous nerve fibres.

Electrical stimulation of the rat lumbar spine induces reflex action potentials in the nerves to the lower abdomen.

STUDY DESIGN: The distribution of the nerve action potentials reflexively elicited by electrical stimulation of the lumbar spine was investigated in rats. OBJECTIVES: To elucidate the relation between the lumbar spine and other body regions that compose the spinal reflex. SUMMARY OF BACKGROUND DATA: The hypothesis was that the ventral portion of the L5-L6 disc spatially corresponds to the groin. METHODS: In Experiments 1 and 2, wire electrodes were placed 1) in the ventral and dorsal portions of the disc, facet joint, and muscle fascia at L5-L6, and 2) in the ventral portions of L3-L4, L4-L5, L5-L6, and L6-S discs. A needle electrode was inserted in the L5-L6 disc by 0.4-mm increments, and action potentials were serially recorded from the genitofemoral nerve. RESULTS: Experiments 1 and 2: Reflex action potentials were elicited in the iliohypogastric (T13 and L1), ilioinguinal (L1), and genitofemoral (L2) nerves. Experiment 1: Stimulation of the disc induced reflex discharges significantly more frequently than stimulation of the facet joint and muscle fascia. Experiment 2: The more cranial the disc stimulated, the more frequently the reflex discharge was induced in the iliohypogastric nerve. Experiment 3: The depth of stimulation did not influence the size of the reflex action potential. CONCLUSIONS: Electrical stimulation of the lumbar disc and facet joint induced reflex discharges in the nerves to the lower abdominal regions. It was postulated that the reflex discharges are related to muscle contraction resulting in referred pain in the loin and groin.

Sensory innervation of the cervical facet joints in rats.

STUDY DESIGN: With a retrograde neurotracing method with Fluoro-Gold (FG; Fluorochrome, Denver, CO), the level of dorsal root ganglions (DRGs) innervating the C1-C2, C3-C4, and C5-C6 facet joints and their pathways were investigated in rats. OBJECTIVES: To clarify the levels of DRGs and parasympathetic nodose ganglions innervating the cervical facet joints and to determine the pathways from the facet joint to DRGs. SUMMARY OF BACKGROUND DATA: Patients with cervical facet lesions and whiplash sometimes experience diffuse neck pain, headache, arm, and shoulder pain, but the pattern of sensory innervation of the facet joint is still unclear. METHODS: Sixty male Sprague-Dawley rats were used. Fluoro-gold crystals (FG) were applied into the C1-C2 (C1-C2 group), C3-C4 (C3-C4 group) and C5-C6 (C5-C6 group) facet joints, and numbers of the labeled neurons in DRGs from C1 to T5 and nodose ganglions were determined. To determine the sensory pathway, bilateral sympathectomy was performed. RESULTS: Neurons labeled with FG were present in the DRGs from C1 through C8 in the C1-C2 group, from C1 to T2 in the C3-C4 group, and from C3 to T3 in the C5-C6 group without sympathectomy. In the nodose ganglions, 17 FG-labeled neurons were present. The number of the labeled neurons after sympathectomy was not significantly different in the C1, C2, and C3 DRGs in the C1-C2 group, in the C3 and C4 DRGs in the C3-C4 group, and in the C5 and C6 DRGs in the C5-C6 group from that in the groups without sympathectomy. In contrast, the number of labeled neurons in the DRGs was significantly less at the other levels than that in the groups without sympathectomy (P < 0.01). CONCLUSION: Sensory nerve fibers of the cervical facet joint were derived from the C1-T3 DRGs. Some sensory nerves from the cervical facet joint entered the paravertebral sympathetic trunks and reached the DRGs at multisegmental levels. The present findings regarding the multisegmental innervation to the facet joint may be of importance in the treatment of facet joint syndrome.

Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.

STUDY DESIGN: Acute noxious stimulation delivered to lumbar muscles and skin of rats was used to study Fos expression patterns in the brain and spinal cord. OBJECTIVES: The present study was conducted to determine the differences in Fos expression in the brain and spinal cord as evoked by stimuli delivered to lumbar muscles and skin in rats. SUMMARY OF BACKGROUND DATA: Patients with low back pain sometimes show psychological symptoms, such as quiescence, loss of interest, decreased activities, appetite loss, and restlessness. The pathway of deep somatic pain to the brain has been reported to be different from that of cutaneous pain. However, Fos expression has not been studied in the central nervous systems after stimulation of low back muscles. METHODS: Rats were injected with 100 L of 5% formalin into the multifidus muscle (deep pain group; n = 10) and into the back skin of the L5 dermatome (cutaneous pain group; n = 10). Two hours after injection, the distribution of Fos-immunoreactive neurons was studied in the brain and spinal cord. RESULTS: Fos-immunoreactive neurons were observed in laminae I-V in the spinal cord in the cutaneous pain group, but they were not seen in lamina II in the deep pain group. In the brain, Fos-immunoreactive neurons were significantly more numerous in the deep pain group than in the cutaneous pain group in the piriform cortex, the accumbens nucleus core, the basolateral nucleus of amygdala, the paraventricular hypothalamic nucleus, the ventral tegmental area, and the ventrolateral periaqueductal gray. CONCLUSION: The finding that Fos-immunoreactive neurons were absent from lamina II of the spinal cord in the deep pain group is similar to that of the projection pattern of the visceral pain pathway. Fos expression in the ventrolateral periaqueductal gray in the deep pain group may represent a reaction of quiescence and a loss of interest, activities, or appetite. Furthermore, the detection of large numbers of Fos-immunoreactive neurons in the core of accumbens nucleus, basolateral nucleus of amygdala, paraventricular hypothalamic nucleus, and ventral tegmental area in the deep pain group may suggest a dominant reaction of dopaminergic neurons to stress, and a different information processing pathway than from that of cutaneous pain.

Primary sensory neurons with dichotomizing axons projecting to the facet joint and the sciatic nerve in rats.

STUDY DESIGN: Dorsal root ganglion (DRG) neurons that have dichotomizing axons to the lumbar facet joint and to the sciatic nerve were investigated in rats using a double fluorescent labeling technique. OBJECTIVES: To clarify the existence of DRG neurons with dichotomizing axons projecting to the lumbar facet joint and to the sciatic nerve in rats. SUMMARY OF BACKGROUND DATA: DRG neurons having dichotomizing axons have been reported in several species and are considered to be related to referred pain. However, such DRG neurons have not been investigated in the lumbar spine. Clinically, pain from the lumbar facet joint is sometimes referred to the lower extremities innervated by the sciatic nerve. METHODS: Two kinds of neurotracers (DiI and FG) were used in the present double-labeling study. DiI crystals were placed in the left L5-L6 facet joint, and FG was applied to the ipsilateral sciatic nerve or along the midline of the L5 dermatome. Bilateral DRGs T13-S1 were observed by fluorescence microscope. RESULTS: DRG neurons double labeled with DiI and FG were recognized only in the ipsilateral DRGs from L3 to L6 levels. Approximately 3% of DRG neurons innervating the L5-L6 facet joint had other axons to the sciatic nerve. By contrast, no double-labeled neurons were observed after FG was applied to the L5 dermatome. CONCLUSIONS: In rats approximately 3% of DRG neurons innervating the lumbar facet joints have dichotomized axons projecting to the sciatic nerve.

Phenotypic inflammation switch in rats shown by calcitonin gene-related peptide immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints.

STUDY DESIGN: The changes in dorsal root ganglion neurons innervating the L5-L6 facet joint were studied using the retrograde neurotransport method and the immunohistochemistry of calcitonin gene-related peptide in an inflammatory model of rats. OBJECTIVES: To determine by inflammatory stimulation the changes in calcitonin gene-related peptide-immunoreactive dorsal root ganglion neurons innervating the L5-L6 facet. SUMMARY OF BACKGROUND DATA: The rat L5-L6 facet joint is innervated from L1-L5 dorsal root ganglia. The presence of calcitonin gene-related peptide-immunoreactive dorsal root ganglion neurons innervating the L5-L6 facet joint has been confirmed, but the changes in the number and distribution of these neurons caused by inflammation have not been studied. METHODS: Retrograde transport of fluorogold was used in 20 rats: 10 in the control group and 10 in the inflammatory group. Using the dorsal approach, fluorogold crystals were injected into the left L5-L6 facet joint. Then 5 days after application, complete Freund's adjuvant (50 microg Mycobacterium butyricum in oil saline emulsion) was injected into the same L5-L6 facet joint (inflammatory group). Of the total fluorogold-labeled dorsal root ganglion neurons from T13-L6, the number and cross-sectional area of the cell profiles of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive neurons in the bilateral dorsal root ganglia of both groups were evaluated. RESULTS: Fluorogold-labeled neurons were distributed throughout the ipsilateral dorsal root ganglia from L1-L5 in both groups. Of the fluorogold-labeled neurons, the ratios of the calcitonin gene-related peptide-immunoreactive L1, L2, L3, L4, and L5 dorsal root ganglion neurons, respectively, were 17%, 24%, 44%, 56%, and 50% in the control group and 50%, 39%, 51%, 61%, and 56% in the inflammatory group. The ratios of the calcitonin gene-related peptide-immunoreactive L1 and L2 dorsal root ganglion neurons labeled by fluorogold were significantly higher in the inflammatory group than in the control group (P < 0.05). The mean cross-sectional area of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive cells from L1-L5 dorsal root ganglia increased from 621 +/- 64 microm2 to 893 +/- 63 microm2 in the inflammatory group (P < 0.01). CONCLUSIONS: The ratio of fluorogold-labeled, calcitonin gene-related peptide-immunoreactive neurons was significantly higher in the L1 and L2 dorsal root ganglia of the inflammatory group than in those of the control group, and the average cross-sectional area of the cells from L1-L5 dorsal root ganglion increased. Associated with the inflammation in the facet joints, the change in calcitonin gene-related peptide-immunoreactive neuron distribution and the phenotypic switch to large neurons may complicate the mechanism of facet joint inflammatory pain.

Sensory innervation of the dorsal portion of the lumbar intervertebral discs in rats.

STUDY DESIGN: The levels of dorsal root ganglions (DRGs) innervating the dorsal portion of the lumbar intervertebral discs from L1-L2 to L4-L5 were investigated in rats by the retrograde transport method. The pathways and functions of nerve fibers supplying the dorsal portion of the discs were investigated by denervation and immuno-histochemistry. OBJECTIVES: To investigate the sensory innervation of the dorsal portion of the lumbar intervertebral discs in rats. SUMMARY OF BACKGROUND DATA: The dorsal portion of the L5-L6 disc has been reported to be innervated multisegmentally, and anesthetic blockade of the paravertebral sympathetic trunks and the L2 spinal nerve can relieve discogenic low back pain. However, sensory innervation of the dorsal portion of the lumbar discs at other levels has not been clarified. METHODS: A retrograde transport of Fluoro-Gold was used. We studied a nonsympathectomy group (n = 44) and a sympathectomy group (n = 50) in which paravertebral sympathetic trunks were resected from L1 to L5 levels. Using a ventral approach, Fluoro-Gold crystals were inserted into the dorsal portion of the L1-L2, L2-L3, L3-L4, and L4-L5 discs. Seven days after surgery, Fluoro-Gold-labeled neurons were counted in the bilateral dorsal root ganglions from T10 to L6. RESULTS: Fluoro-Gold-labeled neurons were distributed in dorsal root ganglions from T11 to L5 levels in the nonsympathectomy group. However, in the sympathectomy group the number of labeled neurons was less than that of the nonsympathectomy group in T11, T12, and T13 dorsal root ganglions of the L1-L2 disc group, in T12, T13, and L1 dorsal root ganglions of the L2-L3 disc group, in T12, T13, L1, and L2 dorsal root ganglions of the L3-L4 disc group, and in T12, T13, L1, and L2 dorsal root ganglions of the L4-L5 disc group. CONCLUSION: The dorsal portion of the lumbar discs from L1-L2 to L4-L5 is multisegmentally innervated by the T11 through L5 dorsal root ganglions. Sensory fibers from the upper dorsal root ganglions innervate the dorsal portion of the discs via the paravertebral sympathetic trunks, although those from the lower dorsal root ganglions innervate via the sinuvertebral nerves. Furthermore, sensory nerve fibers enter the paravertebral sympathetic trunks through the corresponding ramus communicans and reach the dorsal root ganglions via each ramus communicans at the L2 and/or more cranial levels.

Sensory innervation of the dorsal portion of the lumbar intervertebral disc in rats.

STUDY DESIGN: The vertebral levels of dorsal root ganglia innervating the dorsal portion of the L5-L6 intervertebral disc were investigated in rats using a retrograde transport method. The pathways and functions of nerve fibers supplying the dorsal portion of the disc were determined by denervation and immunohistochemistry. OBJECTIVES: The dorsal portion of the lumbar intervertebral disc has been reported to be innervated segmentally, but anesthetic block of the paravertebral sympathetic trunks and the L2 spinal nerve can relieve discogenic low back pain. In the current study, the sensory innervation of the dorsal portion of the L5-L6 intervertebral disc was investigated, because the disc anatomically corresponds to the L4-L5 disc in humans, and the dorsal portion of the human L4-L5 disc is frequently subject to injury that causes low back pain. METHODS: A retrograde transport of Fluoro-Gold (F-G; Fluorochrome, Denver, CO) was used. Subjects included nontreated control (n = 32) and sympathectomized rats in which paravertebral sympathetic trunks were removed from L2 to L3 (n = 9). In a ventral approach, Fluoro-Gold crystals were placed on the dorsal portion of the L5-L6 disc, and labeled neurons in the bilateral dorsal root ganglia from T10 to L6 were counted. RESULTS: Fluoro-Gold crystals did not leak from the dorsal portion of the L5-L6 disc in 14 of the 32 nontreated rats and in 5 of the 9 sympathectomized rats. These rats were used for analysis. Fluro-Gold-labeled neurons were found in dorsal root ganglia from T13 to L6 in the 14 control rats but only from L2 to L6 in the 5 sympathectomized rats. CONCLUSION: The dorsal portion of the L5-L6 disc of rats was shown to be multisegmentally innervated by the T13 to L6 dorsal root ganglia. The sensory fibers from T13, L1, and L2 dorsal root ganglia were shown to innervate the dorsal portion of the L5-L6 disc through the paravertebral sympathetic trunks. In contrast, those from the L3-L6 dorsal root ganglia may innervate the dorsal portion of the L5-L6 disc through the sinuvertebral nerves.

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

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.

Brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating the lumbar facet joints in rats.

The rat L5/6 facet joint is innervated from L1 to L6 by the dorsal root ganglia (DRG). The presence of substance P- and calcitonin gene-related peptide-immunoreactive (ir) DRG neurons innervating the L5/6 facet joint has been demonstrated. However, the presence of brain-derived neurotrophic factor (BDNF)-ir and the vanilloid receptor subtype 1 (VR1)-ir DRG neurons, which relate to inflammatory and burning pain innervating the L5/6 facet joint, has not. Fluoro-gold (FG)-labeled neurons innervating the L5/6 facet joint were distributed throughout the DRGs from T13 to L6 levels. Of the FG-labeled neurons, the proportions of BDNF-ir in L1, L2, L3, L4 and L5 DRG neurons were 9%, 15%, 21%, 17% and 20% and the proportions of VR1-ir L1, L2, L3, L4 and L5 DRG neurons were 8%, 9%, 15%, 16% and 15%, respectively.

Neurones in the dorsal root ganglia of T13, L1 and L2 innervate the dorsal portion of lower lumbar discs in rats. A study using diI, an anterograde neurotracer.

Based on a study using a retrograde neurotracer, we have previously found that the dorsal portion of the L5/6 disc in the rat is multisegmentally innervated by dorsal root ganglia (DRG) from the level of T13 to L6, and that sensory nerve fibres from DRG of T13, L1 and L2 pass through the paravertebral sympathetic trunks. In this study in newborn rats, we injected crystals of 1,1'-dioctadecyl-3,3,3',3'-tetramethylinedocarbocyanine perchlorate (DiI) into the DRG of T13, L1 and L2 and showed DiI-labelled sensory nerve fibres in the dorsal portion of the discs from the level of T13/L1 to L5/6. Our results show that the dorsal portion of the lumbar discs is innervated by the DRG from levels T13 to L2.

Dorsal root ganglion neurones with dichotomising afferent fibres to both the lumbar disc and the groin skin. A possible neuronal mechanism underlying referred groin pain in lower lumbar disc diseases.

Dorsal root ganglion neurones with dichotomising axons are present in several species and are considered to play a role in referred pain. Clinically, patients with lesions in the lower lumbar discs occasionally complain of pain in the groin. We investigated the existence of dichotomising afferent neurones projecting axons both to the lumbar disc and to the groin skin, using the double fluorescent-labelling technique in rats. We observed neurones labelled with a tracer applied at the ventral portion of the LS-L6 disc and another tracer placed on the groin skin in L1 and L2 dorsal root ganglia. Our results showed that the double-labelled neurones had peripheral axons which dichotomised into both the LS-L6 disc and the groin skin, indicating the convergence of afferent sensory information from the disc and groin skin. Our findings provide a possible neuroanatomical mechanism for referred groin pain in patients with disc lesions.