Nobuyasu Ochiai

Pain-related sensory innervation in monoiodoacetate-induced osteoarthritis in rat knees that gradually develops neuronal injury in addition to inflammatory pain

BackgroundThe exact mechanism of knee osteoarthritis (OA)-associated pain is unclear, whereas mixed evidence of inflammatory pain and neuropathic pain has been noted. We aimed to investigate pain-related sensory innervation in a monoiodoacetate (MIA)-induced model of OA.MethodsSixty of seventy female Sprague Dawley rats of six week-old underwent intra-articular MIA and fluorogold (FG) retrograde neurotracer injection into their right (ipsilateral) knee, while their left knees were treated with FG in saline as a control (contralateral knee). Other rats were treated with FG only bilaterally, and used as controls. Rats were evaluated for tactile allodynia using von Frey hairs. Proinflammatory mediators in the knee soft tissues, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nerve growth factor (NGF), were quantified using ELISAs to evaluate inflammation in the knee after 1, 4, 7,14,21, and 28 days post injection:. Dorsal root ganglia (DRG) were immunostained for three molecules after 7,14,21, and 28 days post injection: calcitonin gene-related peptide (CGRP), a marker of inflammatory pain; and activating transcription factor-3 (ATF3) and growth associated protein-43 (GAP43), as markers for nerve injury and regenerating axons. The distribution of microglia in the spinal cord were also evaluated, because they have been reported to increase in neuropathic pain states. These evaluations were performed up to 28 days postinjection. P < 0.05 was considered significant.ResultsProgressive tactile allodynia and elevated cytokine concentrations were observed in ipsilateral knees. CGRP-immunoreactive (-ir) ipsilateral DRG neurons significantly increased, peaking at 14 days postinjection, while expression of FG-labeled ATF3-ir or ATF3-ir GAP43-ir DRG neurons significantly increased in a time-dependent manner. Significant proliferation of microglia were found with time in the ipsilateral dorsal horn.ConclusionsPain-related characteristics in a MIA-induced rat OA model can originate from an inflammatory pain state induced by the local inflammation initiated by inflammatory cytokines, and that state will be followed by gradual initiation of neuronal injury, which may induce the neuropathic pain state.

Comparison of teriparatide and bisphosphonate treatment to reduce pedicle screw loosening after lumbar spinal fusion surgery in postmenopausal women with osteoporosis from a bone quality perspective.

Study Design. Prospective study. Objective. To examine the efficacy of teriparatide or bisphosphonate treatment to reduce pedicle screw (PS) loosening after instrumented lumbar posterolateral fusion in postmenopausal women with osteoporosis. Summary of Background Data. Failure of fixation caused by loosening of PSs in osteoporosis is a problem in spinal surgery. Oral administration of bisphosphonate or intermittent injection of parathyroid hormone treatment increases bone mass and reduces the risk of osteoporotic vertebral fractures. Although these treatments may be factor in improving bone quality, a clinical study of the efficacy of bisphosphonate or parathyroid hormone for reducing PS loosening that addresses the quality of the bone marrow and pedicle cortex has not yet been reported. Methods. Sixty-two women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 3 groups: a teriparatide group (daily subcutaneous injection of 20 &mgr;g of teriparatide, n = 20), a bisphosphonate group (daily oral administration 2.5 mg of risedronate, n = 20), and a control group (without medication for osteoporosis, n = 22). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Loosening of PSs and surgical outcome were evaluated radiographically, clinically, and by computed tomography 12 months after surgery. Results. At 12-month follow-up, the incidence of PS loosening was 7% to 13% in the teriparatide group, 13% to 26% in the risedronate group, and 15% to 25% in the control group. The incidence of PS loosening in the teriparatide group was significantly lower than that in the risedronate or the control group (P < 0.05). In contrast, the extent of PS loosening in the risedronate group was not significantly different from that in the control group (P > 0.05). Conclusion. Our findings suggest that administration of teriparatide increased the quality of the lumbar spine bone marrow and pedicle cortex. Level of Evidence: 3

Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study.

Study Design. Prospective randomized trial. Objective. To examine the effect of the tumor necrosis factor alpha (TNF-&agr;) inhibitor, etanercept, on radicular pain by its epidural administration onto spinal nerves in patients with lumbar spinal stenosis. Summary of Background Data. TNF-&agr; is thought to play a crucial role in the radicular pain caused by lumbar disc herniation and spinal stenosis. Intravenous infusion of infliximab for sciatica has been examined in 2 studies; however, the results were equivocal. Methods. Eighty patients with low back and radicular leg pain were investigated. We diagnosed the patients by physical examination, and X-ray and magnetic resonance imaging. In 40 patients, we epidurally administered 2.0 mL of lidocaine and 10 mg of etanercept onto the affected spinal nerve, and 2.0 mL of lidocaine and 3.3 mg of dexamethasone was used in 40 patients. Low back pain, leg pain, and leg numbness were evaluated using a visual analogue scale (VAS) and Oswestry Disability Index (ODI) score before and for 1 month after epidural administration. Results. Low back pain, leg pain, and leg numbness in the 2 groups were not significantly different before epidural administration. Epidural administration of etanercept was more effective than dexamethasone for leg pain (3 days, and 1, 2, and 4 weeks: P < 0.05), low back pain (3 days, and 1 and 2 weeks: P < 0.05), and leg numbness (3 days, and 1 and 2 weeks: P < 0.05). No adverse event was observed in either group. Conclusion. Our results indicate that epidural administration of a TNF-&agr; inhibitor onto the spinal nerve produced pain relief, but no adverse event. TNF-&agr; inhibitors may be useful tools for the treatment of radicular pain caused by spinal stenosis.

Existence of a Neuropathic Pain Component in Patients with Osteoarthritis of the Knee

Purpose Pain from osteoarthritis (OA) is generally classified as nociceptive (inflammatory). Animal models of knee OA have shown that sensory nerve fibers innervating the knee are significantly damaged with destruction of subchondral bone junction, and induce neuropathic pain (NP). Our objective was to examine NP in the knees of OA patients using painDETECT (an NP questionnaire) and to evaluate the relationship between NP, pain intensity, and stage of OA. Materials and Methods Ninety-two knee OA patients were evaluated in this study. Pain scores using Visual Analogue Scales (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), painDETECT, duration of symptoms, severity of OA using the Kellgren-Lawrence (KL) system, and amount of joint fluid were evaluated and compared using a Spearmans correlation coefficient by rank test. Results Our study identified at least 5.4% of our knee OA patients as likely to have NP and 15.2% as possibly having NP. The painDETECT score was significantly correlated with the VAS and WOMAC pain severity. Compared with the painDETECT score, there was a tendency for positive correlation with the KL grade, and tendency for negative correlation with the existence and amount of joint fluid, but these correlations were not significant. Conclusion PainDETECT scores classified 5.4% of pain from knee OA as NP. NP tended to be seen in patients with less joint fluid and increased KL grade, both of which corresponded to late stages of OA. It is important to consider the existence of NP in the treatment of knee OA pain.

Results of surgery for discogenic low back pain: a randomized study using discography versus discoblock for diagnosis.

Study Design. Randomized, controlled study. Objective. To evaluate the diagnosis of discogenic low back pain (LBP) with discography and discoblock. Summary of Background Data. Discogenic LBP is usually diagnosed by magnetic resonance imaging and discography. However, the reliability of discography is controversial. Previously, we reported the usefulness of discoblock with bupivacaine for diagnosis, and discoblock improved the results of anterior interbody fusion surgery. However, that study was not a randomized, controlled study. Therefore, the purpose of the current study was to compare the results of surgery after diagnosis of LBP by discography and discoblock. Methods. Patients (n = 42) with severe LBP showing L4–L5 or L5–S1 disc degeneration on magnetic resonance imaging were evaluated by discography (1.5 mL of contrast medium) or discoblock (intradisc injection of 0.75 mL of 0.5% bupivacaine). We randomized the patients in turn. Anterior discectomy and interbody fusion were performed in patients who responded to the diagnostic procedures. The visual analogue scale score (0, no pain; 100, worst pain), Japanese Orthopedic Association Score (0, worst pain; 3, no pain), Oswestry Disability Index, and patient satisfaction before and 3 years after surgery were recorded and compared between groups. Results. Twelve patients did not show pain provocation by discography or pain relief by discoblock and were excluded. Fifteen patients who showed pain provocation by discography and 15 patients who experienced pain relief with discoblock were evaluated. Rates of improvement in the visual analogue scale score, Japanese Orthopedic Association Score, and Oswestry Disability Index score in the discoblock group were significantly higher than those in the discography group (P < 0.05) from baseline to 3 years after surgery. Three patients were dissatisfied with surgery after discography compared with one patient after discoblock. Conclusion. Pain relief after injection of a small amount of bupivacaine into the painful disc was a useful tool for the diagnosis of discogenic LBP compared with discography.

Teriparatide accelerates lumbar posterolateral fusion in women with postmenopausal osteoporosis: prospective study.

Study Design. Prospective trial. Objective. To examine the clinical efficacy of teriparatide for bone union after instrumented lumbar posterolateral fusion using local bone grafting in women with postmenopausal osteoporosis. Summary of Background Data. Intermittent parathyroid hormone (PTH) treatment increases bone mass and reduces the risk for osteoporotic vertebral fractures. Recombinant human PTH (1–34) has already been approved as a treatment for severe osteoporosis. Preclinical data support the efficacy of PTH for lumbar spinal fusion. However, clinical results of PTH for spinal fusion have not yet been reported. Methods. Fifty-seven women with osteoporosis diagnosed with degenerative spondylolisthesis were divided into 2 treatment groups, a teriparatide group (n = 29; daily subcutaneous injection of 20 &mgr;g of teriparatide) and a bisphosphonate group (n = 28; weekly oral administration of 17.5 mg of risedronate). All patients underwent decompression and 1- or 2-level instrumented posterolateral fusion with a local bone graft. Fusion rate, duration of bone union, and pain scores were evaluated 1 year after surgery. Results. Pain scores improved after surgery; however, no significant difference was noted between the groups after surgery. The rate of bone union was 82% in the teriparatide group and 68% in the bisphosphonate group. Average duration of bone union was 8 months in the teriparatide group and 10 months in the bisphosphonate group. The rate of bone union and average of duration of bone union in the teriparatide group patients were significantly superior to those in the bisphosphonate group. Conclusion. Daily subcutaneous injection of teriparatide for bone union using local bone grafting after instrumented lumbar posterolateral fusion in women with postmenopausal osteoporosis was more effective than oral administration of bisphosphonate.

In vivo 3-dimensional analysis of scapular kinematics: comparison of dominant and nondominant shoulders

BACKGROUND Alterations in scapular motion frequently are seen in association with various shoulder disorders. It is common clinically to compare the pathological shoulder with the contralateral shoulder, in spite of arm dominance, to characterize the disorder. However, there have been few articles that test the underlying assumption that dominant and nondominant shoulders exhibit comparable dynamic kinematics. The purpose of this study was to compare the 3-dimensional (3-D) scapular kinematics of dominant and nondominant shoulders during dynamic scapular plane elevation using 3-D-2-D (2-dimensional) registration techniques. MATERIALS AND METHODS Twelve healthy males with a mean age of 32 years (range, 27-36) were enrolled in this study. Bilateral fluoroscopic images during scapular plane elevation and lowering were taken, and CT-derived 3-D bone models were matched with the silhouette of the bones in the fluoroscopic images using 3-D-2-D registration techniques. Angular values of the scapula and scapulohumeral rhythm were compared between dominant and nondominant shoulders with statistical analysis. RESULTS There was a significant difference in upward rotation angles between paired shoulders (P < .001), while significant differences were not found in the other angular values and scapulohumeral rhythm. The dominant scapulae were 10° more downwardly rotated at rest and 4° more upwardly rotated during elevation compared to the nondominant scapulae. DISCUSSION/CONCLUSION Scapular motion was not the same between dominant and nondominant arms in healthy subjects. The dominant scapula was rotated further downward at rest and reached greater upward rotation with abduction. These differences should be considered in clinical assessment of shoulder pathology.

Dynamic In Vivo Glenohumeral Kinematics During Scapular Plane Abduction in Healthy Shoulders

STUDY DESIGN Controlled laboratory study. OBJECTIVES To measure superior/inferior translation and external rotation of the humerus relative to the scapula during scapular plane abduction using 3-D/2-D model image registration techniques. BACKGROUND Kinematic changes in the glenohumeral joint, including excessive superior translation of the humeral head and inadequate external rotation of the humerus, are believed to be a possible cause of shoulder impingement. Although many researchers have analyzed glenohumeral kinematics with various methods, few articles have assessed dynamic in vivo glenohumeral motion. METHODS Twelve healthy males with a mean age of 32 years (range, 27-36 years) were enrolled in this study. Fluoroscopic images of the dominant shoulder during scapular plane elevation were taken, and computed tomography-derived 3-D bone models were matched with the silhouette of the bones in the fluoroscopic images using 3-D/2-D model image registration techniques. The kinematics of the humerus relative to the scapula were determined using Euler angles. RESULTS On average, there was 2.1 mm of initial humeral translation in the superior direction from the starting position to 105° of humeral elevation. Subsequently, an average of 0.9 mm of translation in the inferior direction occurred between 105° and maximum arm elevation. The average amount of external rotation of the humerus was 14° from the starting position to 60° of humeral elevation. The humerus then rotated internally an average 9° by the time the shoulder reached maximum elevation. These changes in superior/inferior translation and external/internal rotation were statistically significant (P<.001 and P = .001, respectively), based on 1-way repeated-measures analysis of variance. CONCLUSION The observed glenohumeral translations and rotations characterize healthy shoulder function and serve as a preliminary foundation for quantifying pathomechanics in the presence of glenohumeral joint disorders.

Risedronate decreases bone resorption and improves low back pain in postmenopausal osteoporosis patients without vertebral fractures.

Elderly postmenopausal women who have osteoporosis sometimes experience low back pain, however, the relationship between low back pain and osteoporosis in the absence of vertebral fractures remains unclear. We examined the relationship between bone mineral density (BMD), bone resorption and low back pain in elderly female patients who did not have osteoporotic vertebral fractures. The average BMD was 0.675 g/cm(2) when assessed by dual-energy X-ray absorptiometry (DEXA). Patients were excluded from the study if they had vertebral fractures revealed by radiography, CT scans or MRI. Bisphosphonate (risedronate) was administered for 4 months. The visual analogue scale (VAS) pain score, Roland Morris Disability Questionnaire (RDQ), Short Form-36 (SF-36) questionnaire, BMD and N-terminal telopeptide of type I collagen (NTx; a marker for bone resorption) were examined before and after treatment. DEXA did not increase significantly, but serum and urinary NTx were decreased (-51.4% and -62.0%, respectively) after 4 months of risedronate treatment (p<0.01). The assessment was repeated using the VAS score, RDQ and SF-36, which revealed an improvement after risedronate treatment (p<0.01). A decrease in serum and urinary NTx was associated with improvement of low back pain, suggesting that despite the absence of vertebral fractures, bone resorption due to osteoporosis may cause low back pain.

Diffusion magnetic resonance imaging to differentiate degenerative from infectious endplate abnormalities in the lumbar spine.

Study Design. A retrospective observational study of healthy volunteers and patients with degenerative and infectious endplate abnormalities in the lumbar spine. Objectives. Our purpose was to evaluate the usefulness of diffusion-weighted imaging (DWI) for the differentiation of degenerative and infectious endplate abnormalities using 1.5-T magnetic resonance imaging (MRI). Summary of Background Data. DWI can provide valuable structural information about tissues that may be useful for clinical applications in differentiation between degenerative and infectious endplate abnormalities. Methods. Sixteen consecutive patients with endplate abnormalities that was detected by MRI of the lumbar spine, and 15 healthy volunteers were studied. DWI was performed using whole-body imaging with background body signal suppression with a b value of 1000 s/mm2. Apparent diffusion coefficient values of normal and abnormal vertebral bone marrow were calculated. Results. Twenty-nine vertebral abnormalities were found in 16 patients. Nine vertebral abnormalities in 5 patients were because of infections and 20 vertebral abnormalities in 11 patients were because of degenerative changes; 7 levels were classified as Modic type 1, 7 levels as type 2, and 6 levels as type 3. DWI showed hyperintensity in all patients with infection, similar to that used in positron emission tomography, but not in the intervertebral spaces of any patients with degenerative disease. Apparent diffusion coefficient values of infectious bone marrowwere significantly higher than normal and degenerative bone marrow. Conclusion. DWI is useful for differentiation of degenerative and infectious endplate abnormalities. Moreover, MRI is widely used clinically because of the lack of ionizing radiation, low cost, and fast imaging time as compared with positron emission tomography. Therefore, DWI has the potential to be used as a screening tool.