It was reported that nerve fibers were present in the inner part of lumbar intervertebral discs from patients with discogenic pain. Because there are no nerve fibers in the inner part of annulus fibrosus in normal condition, this finding suggests nerve ingrowth into the disc may be a cause of discogenic pain. Disc degeneration is often asymptomatic, thus, to understand the differences between symptomatic and asymptomatic disc, it is necessary to understand the pathogenesis of discogenic pain. We recently revealed that over 90% of the nociceptive dorsal root ganglion (DRG) neurons innervating the disc are sensitive to nerve growth factor (NGF), which is related to inflammatory pain. This indicates that discogenic pain is closely related to inflammation and NGF may play a key role. The increase of inflammatory mediators in symptomatic discs has been reported; we therefore studied the effects of disc inflammation and found that it induces sensitization of disc-innervating neurons and nerve ingrowth into the disc. More recently, it was shown that annular rupture induces nerve ingrowth, an increase of inflammatory mediators in the disc, and upregulation of calcitonin gene-related peptide, a pain-related molecule in DRGs. These findings led us to believe that annular rupture triggers inflammation and nerve ingrowth, inflammatory mediators then further promote nerve ingrowth into the disc and sensitization of disc-innervating neurons, and discogenic pain finally becomes chronic. NGF, found in symptomatic discs, may act as a key factor in generating chronic discogenic pain by sensitizing disc-innervating neurons and stimulating nerve ingrowth into the disc.
Calcitonin Gene-Related Peptide ; Diagnosis-Related Groups ; Ganglia, Spinal ; Humans ; Inflammation ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Nerve Fibers ; Nerve Growth Factor ; Neurons ; Rupture ; Up-Regulation

Triplet surveys were conducted in the city of Xi' an and two villages (one in the vicinity and the other at a distance) in Shaanxi Province in China in October-November (when agricultural activitis were low), 1997, to elucidate nutrient intakes with a focus on possible urban-rural differences. Total food duplicate samples were collected from non-smoking and non-habitually drinking adult healthy women (about 50 subjects per site and 149 in total). The nutrient intakes were estimated from the weight of food items in reference to national food composition tables. On average, the women took 1873 kcal energy, 54 g protein and 37 g lipid per day, with a lipid energy ratio of18.4%. Both excess and insufficient energy intake was observed as a result of food intake analysis and body mass index determination. With regard to minor nutrient intakes, insufficiency was serious in the case of calcium, vitamin A and vitamin B2, but not with iron. Whereas dependency on plant foods for sources of energy and protein was common to the three regions, Xi' an people consumed more animal foods than those in the villages. Intake of fish and shellfish was quite low throughout the three regions. Among the four types of cereals, wheat was consumed most substantially in the three regions and in three meals (except for the village where people essentially did not take lunch in reflection of low agricultural activities), whereas rice was consumed more in Xi' an than in the two villages. Maize consumption was higher in the two villages (especially for breakfast) than in the city.In contrast, foxtail millet (although in small amounts) was taken primarily in Xi'an and only at the time of breakfast.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To investigate the effect of spinal correction on respiratory muscle strength in patients with Duchenne muscular dystrophy (DMD). OVERVIEW OF LITERATURE: Several studies have reported that scoliosis correction in patients with DMD does not improve pulmonary function. In these studies, pulmonary function was evaluated using the traditional spirometric values of percent vital capacity (%VC) and percent forced vital capacity (%FVC). However, traditional spirometry may not be suitable for patients with DMD because the results can be influenced by patient fatigue or level of understanding. Therefore, we evaluated respiratory function focusing on respiratory muscle strength using maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP), in addition to %VC and %FVC. METHODS: We retrospectively reviewed 16 patients with DMD who underwent spinal correction surgery between 2006 and 2011 at Kitasato University Hospital. All patients were males, and the mean age was 13.5 years. Respiratory muscle strength was evaluated using MIP, MEP, and SNIP. Measurements were obtained preoperatively and at 1 and 6 months postoperatively, and %VC and %FVC were obtained preoperatively and within 6 months postoperatively. RESULTS: The mean preoperative and postoperative %VC values were 54.0% and 51.7%, whereas the mean %FVC values were 53.9% and 53.2%, respectively. The mean MIP, MEP, and SNIP values obtained preoperatively and at 1 and 6 months postoperatively were as follows: MIP, 40.5, 42.7 and 47.2 cm H₂O; MEP, 26.0, 28.0, and 29.0 cm H₂O; and SNIP, 33.4, 33.0, and 33.0 cm H₂O; respectively. The mean MIP and MEP values significantly improved postoperatively. There were no significant differences in SNIP, %VC, or %FVC preand postoperatively. CONCLUSIONS: By focusing on respiratory muscle strength, our results suggest that scoliosis correction in patients with DMD might have a favorable effect on respiratory function.
Cohort Studies ; Fatigue ; Humans ; Male ; Muscular Dystrophy, Duchenne* ; Respiratory Muscles* ; Retrospective Studies ; Scoliosis* ; Spirometry ; Vital Capacity

PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.
Animals ; Antibodies ; Calcitonin Gene-Related Peptide/metabolism ; Disease Models, Animal ; Ganglia, Spinal/*metabolism ; Intervertebral Disc/*drug effects/*injuries ; Intervertebral Disc Degeneration/metabolism ; Low Back Pain/*physiopathology ; Lumbar Vertebrae/injuries ; Male ; NAV1.7 Voltage-Gated Sodium Channel/*metabolism ; Neurons/*metabolism ; Pain/metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbamidines

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats. METHODS: Mechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry. RESULTS: Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01). CONCLUSIONS: The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.
Animals ; Cytokines ; Diagnosis-Related Groups ; Ganglia, Spinal* ; Hyperalgesia ; Immunohistochemistry ; Negotiating ; Neurons ; NF-kappa B ; RANK Ligand* ; Rats* ; Sciatic Nerve* ; Up-Regulation

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. METHODS: The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. RESULTS: Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). CONCLUSIONS: Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
Animals ; Antibodies ; Astrocytes ; Calcium ; Cytokines ; Ganglia, Spinal ; Horns ; Hyperalgesia ; Inflammation ; Microglia ; Neuroglia ; Prostaglandins ; Rats* ; Sciatic Nerve* ; Spinal Cord* ; Surgical Instruments ; Up-Regulation*

PURPOSE: Surgery for lumbar spinal degeneration disease is widely performed. While posterior decompression and fusion are popular, anterior lumbar interbody fusion (ALIF) is also used for treatment. Extreme lateral interbody fusion (XLIF) is commonly used for noninvasive ALIF; however, several complications, such as spinal nerve and psoas muscle injury, have been reported. In the current study, we examined the clinical efficacy and complications of oblique lateral interbody fusion (OLIF) for lumbar spinal degeneration disease. MATERIALS AND METHODS: Thirty-five patients with degenerated spondylolisthesis, discogenic pain, and kyphoscoliosis were examined. All patients underwent OLIF surgery (using a cage and bone graft from the iliac crest) with or without posterior decompression, without real-time electromyography monitoring. Posterior screws were used in all patients. Visual analog scale (VAS) score and Oswestry Disability Index (ODI) were evaluated before and 6 months after surgery. Surgical complications were also evaluated. RESULTS: Pain scores significantly improved after surgery, compared to those before surgery (p<0.05). There was no patient who underwent revision surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. Few patients showed symptoms from psoas invasion. CONCLUSION: OLIF surgery produced good surgical results without any major complication.
Adult ; Aged ; Decompression, Surgical/*methods ; Electromyography ; Female ; Humans ; Lumbar Vertebrae/surgery ; Male ; Middle Aged ; Pain ; Pain Measurement ; Scoliosis/*surgery ; Spinal Diseases/surgery ; Spinal Fusion/*methods ; Spondylolisthesis/*surgery ; Treatment Outcome ; Young Adult

STUDY DESIGN: Prospective study of changes in intervertebral disc degeneration after injection of bupivacaine. PURPOSE: To examine whether injection of bupivacaine into human intervertebral discs accelerates their degeneration. OVERVIEW OF LITERATURE: Bupivacaine is commonly used for therapy and diagnosis of discogenic low back pain. However, several in vitro studies have reported toxic effects of bupivacaine to disc cells. We sought to evaluate whether this finding is clinically relevant. METHODS: We selected 46 patients with low back pain who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging (MRI) (discography group, n=18), discoblock group (injection of bupivacaine, n=18), and a control group, n=10). There were no significant differences in baseline characteristics across the 3 groups. The two experimental groups underwent either discography or anesthetic discoblock, respectively. All three groups were followed up 5 years after the examination. RESULTS: At 5 years follow-up, there was no significant difference in the rate of disc degeneration among the 3 groups (p>0.1). Moreover, X-ray images showed that there was no significant difference in disc height, range of motion, or translation between flex and extension position (p>0.1). CONCLUSIONS: In conclusion, radiologic and MRI findings did not show acceleration of intervertebral disc degeneration at 5 years after a single injection of bupivacaine into human discs.
Bupivacaine ; Follow-Up Studies ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain ; Lumbar Vertebrae ; Magnetic Resonance Imaging ; Prospective Studies ; Range of Motion, Articular

PURPOSE: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. MATERIALS AND METHODS: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. RESULTS: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. CONCLUSION: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
Back Pain ; Bupivacaine* ; Diagnosis ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain* ; Magnetic Resonance Imaging ; Methods ; Spinal Fusion ; Spine

PURPOSE: To introduce a new simple technique using suture anchors and ceramic spacers to stabilize the elevated laminae in open-door cervical laminoplasty. Although ceramic spacers were placed in the opened laminae and fixed with nylon threads in this series, it was occasionally difficult to fix the nylon threads to the lateral mass. MATERIALS AND METHODS: Study 1: A preliminary study was conducted using a suture anchor system. Sixteen consecutive patients who underwent surgery for cervical myelopathy were prospectively examined. Study 2: The second study was performed prospectively to evaluate the feasibility of this new technique based on the result of the preliminary study. Clinical outcomes were examined in 45 consecutive patients [cervical spondylotic myelopathy (CSM)] and 43 consecutive patients (OPLL). The Japanese Orthopedic Association scoring system (JOA score), axial neck pain, and radiological findings were analyzed. RESULTS: 1) In one case, re-operation was necessary due to dislodgement of the ceramic spacer following rupture of the thread. 2) In all patients, postoperative CT scans showed that the anchors were securely inserted into the bone. In the CSM group, the average JOA score improved from 9.5 points preoperatively to 13.3 at follow-up (recovery 51%). In the OPLL group, the average JOA score improved from 10.1 (5-14) points preoperatively to 14.4 (11-16) at follow-up (recovery 62%). There were no serious complications. CONCLUSION: The use of the suture anchor system made it unnecessary to create a hole in the lateral mass and enabled reliable and faster fixation of the HA spacers in open-door laminoplasty.
Adult ; Aged ; *Ceramics ; Cervical Vertebrae/radiography ; Feasibility Studies ; Female ; Follow-Up Studies ; Humans ; Laminoplasty/*methods ; Male ; Middle Aged ; Postoperative Period ; Prospective Studies ; Spinal Cord Diseases/*surgery ; Suture Anchors ; *Sutures ; Tomography, X-Ray Computed ; Treatment Outcome