Assessment of a Discogenic Pain Animal Model Induced by Applying Continuous Shear Force to Intervertebral Discs.

BACKGROUND: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed. OBJECTIVES: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force. STUDY DESIGN: Animal study utilizing rats in vivo model of a shear force device. METHODS: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma. RESULTS: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group. LIMITATIONS: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods. CONCLUSIONS: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.

Pharmacotherapies to prevent epidural fibrosis after laminectomy: a systematic review of in vitro and in vivo animal models.

BACKGROUND CONTEXT: Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate epidural fibrosis by suppressing proliferation and activation of fibroblasts, inflammation, and angiogenesis, and inducing apoptosis. PURPOSE: We reviewed and tabulated pharmaceuticals with their respective signaling axes implicated in reducing epidural fibrosis. Additionally, we summarized current literature for the feasibility of novel biologics and microRNA to lessen epidural fibrosis. STUDY DESIGN/SETTING: Systematic Review. METHODS: According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, nonrelevant articles, and insufficient detail of drug mechanism. RESULTS: We obtained a total of 2,499 articles from PubMed and Embase databases. After screening the articles, 74 articles were finally selected for the systematic review and classified based on the functions of drugs and microRNAs which included inhibition of fibroblast proliferation and activation, pro-apoptosis, anti-inflammation, and antiangiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis. CONCLUSION: This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy. CLINICAL SIGNIFICANCE: We expect that our review would enable researchers and clinicians to better understand the mechanism of anti-fibrosis drugs for the clinical application of epidural fibrosis therapies.

Targeting oxidative stress with amobarbital to prevent intervertebral disc degeneration: Part I. in vitro and ex vivo studies.

BACKGROUND: Mounting evidence that oxidative stress contributes to the pathogenesis of intervertebral disc (IVD) degeneration (IDD) suggests that therapies targeting oxidative stress may slow or prevent disease progression. PURPOSE: The objective of this study was to investigate the inhibitory effects of amobarbital (Amo) on the mitochondria of nucleus pulposus (NP) cells under tert-butyl hydrogen peroxide (tBHP)-induced oxidative stress or in NP tissues under oxidative stress from tissue injury as a means of identifying therapeutic targets for IDD. STUDY DESIGN/SETTING: We tested the effects inhibiting mitochondria, a major source of oxidants, with Amo in NP cells subjected to two different forms of insult: exposure to tBHP, and physical injury induced by disc transection. N-acetylcysteine (NAC), an antioxidant known to protect NP cells, was compared to the complex I inhibitor, Amo. METHODS: NP cells were pre-treated for 2 hours with Amo, NAC, or both, and then exposed to tBHP for 1 hour. Apoptosis, necrosis, and reactive oxygen species (ROS) production were assessed using confocal microscopy and fluorescent probes (Annexin V, propidium iodide, and MitoSox Red, respectively). The activation of mitogen-activated protein kinases (MAPKs) involved in oxidative stress responses were interrogated by confocal imaging of immunofluorescence stains using phospho-specific antibodies to extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK), and p38. Mitochondrial function was assessed by imaging JC-1 staining, a probe for membrane potential. RESULTS: Amo was modestly more protective than NAC by some measures, while both agents improved mitochondrial function and lowered tBHP-induced apoptosis, necrosis, and ROS production. Activation of MAPK by tBHP was significantly suppressed by both drugs. Physically injured IVDs were treated immediately after transection with Amo or NAC for 24 hours, and then stained with dihydroethidium (DHE), a fluorescent probe for ROS production. Immunofluorescence was used to track the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor that induces the expression of antioxidant genes. Amo and NAC significantly reduced ROS production and increased Nrf2 expression. CONCLUSION: These findings suggest that the progression of IDD may be forestalled by Amo via protection of NP cells from oxidative stress following IVD injury. CLINICAL SIGNIFICANCE: This study will define the extent to which a novel, minimally invasive procedure targeting oxidative stress in NP cells can augment surgical interventions intended to retard IVD degeneration.

Triphenylphosphonium derivatives disrupt metabolism and inhibit melanoma growth in vivo when delivered via a thermosensitive hydrogel.

Despite dramatic improvements in outcomes arising from the introduction of targeted therapies and immunotherapies, metastatic melanoma is a highly resistant form of cancer with 5 year survival rates of <35%. Drug resistance is frequently reported to be associated with changes in oxidative metabolism that lead to malignancy that is non-responsive to current treatments. The current report demonstrates that triphenylphosphonium(TPP)-based lipophilic cations can be utilized to induce cytotoxicity in pre-clinical models of malignant melanoma by disrupting mitochondrial metabolism. In vitro experiments demonstrated that TPP-derivatives modified with aliphatic side chains accumulated in melanoma cell mitochondria; disrupted mitochondrial metabolism; led to increases in steady-state levels of reactive oxygen species; decreased total glutathione; increased the fraction of glutathione disulfide; and caused cell killing by a thiol-dependent process that could be rescued by N-acetylcysteine. Furthermore, TPP-derivative-induced melanoma toxicity was enhanced by glutathione depletion (using buthionine sulfoximine) as well as inhibition of thioredoxin reductase (using auranofin). In addition, there was a structure-activity relationship between the aliphatic side-chain length of TPP-derivatives (5-16 carbons), where longer carbon chains increased melanoma cell metabolic disruption and cell killing. In vivo bio-distribution experiments showed that intratumoral administration of a C14-TPP-derivative (12-carbon aliphatic chain), using a slow-release thermosensitive hydrogel as a delivery vehicle, localized the drug at the melanoma tumor site. There, it was observed to persist and decrease the growth rate of melanoma tumors. These results demonstrate that TPP-derivatives selectively induce thiol-dependent metabolic oxidative stress and cell killing in malignant melanoma and support the hypothesis that a hydrogel-based TPP-derivative delivery system could represent a therapeutic drug-delivery strategy for melanoma.

Biomechanical rigidity of cadaveric cervical spine with posterior versus combined posterior and anterior instrumentation.

OBJECT: In patients with cervical stenosis with myelopathy, posterior instrumentation following cervical laminectomy has been shown to reduce the incidence of postoperative instability and kyphosis. However, the indications for posterior plus anterior instrumentation are not always obvious, and using both posterior and anterior instrumentation routinely is unnecessary and excessive. This study examines the rigidity of the intact isolated cadaveric cervical spine, after C4-6 laminectomy, with posterior lateral mass instrumentation, and following posterior plus anterior instrumentation. METHODS: Ten fresh-frozen human cadaveric cervical spines from C-1 to T-2 were potted in the neutral position, and retroreflective markers were placed on C-3 and C-7. Specimens were mounted on a biomechanical testing frame, and angular rotations of C-3 relative to C-7 were measured. Pure moments of 0, 0.3, 0.6, 0.9, and 1.2 Nm were applied at C-2 in all 3 planes. Each specimen was load tested as follows: 1) in the intact state; 2) after C4-6 laminectomy; 3) with C3-7 lateral mass instrumentation; and 4) with C3-7 posterior plus anterior instrumentation. RESULTS: Laminectomy was not associated with a significant increase in motion compared with the intact state with any load or in any direction. Instrumentation was associated with reduction in motion in all directions, and there was no significant difference in posterior versus combined posterior and anterior instrumentation. CONCLUSIONS: Rigidity imparted to the cervical spine by a 5-level posterior lateral mass fixation is not augmented by anterior instrumentation.

Preclinical studies of ropivacaine extended-release from a temperature responsive hydrogel for prolonged relief of pain at the surgical wound.

Postoperative pain is a common form of acute pain that has been treated commonly by local anesthetics through regional nerve blocking. In this study, a series of experiments were conducted using rats to investigate the pharmacokinetic, distribution, and efficacy of a temperature responsive hydrogel-based drug delivery device (PF-72) containing ropivacaine (0.75%) for extended relief of postoperative pain by allowing the prolonged release of ropivacaine. When the ropivacaine was administered using PF-72, its concentration-time curve (AUClast) and peak concentration (Cmax) were 577.0 h*ng/mL and 271.9 ng/mL, respectively. In contrast when the ropivacaine solution was administered using saline solution, its AUClast and Cmax were 982.8 h*ng/mL and 423.6 ng/mL, respectively. In the tissue distribution study, the peak concentration and mean area under the curve of the ropivacaine in injection area (target tissue) were found about 2-fold higher in the case of PF-72 compared with the case of conventional ropivacaine solution. These results clearly demonstrate the capability of PF-72 hydrogel to retain the ropivacaine at the injection site for an extended period. Effective extended (at least 24 h) pain relief of ropivacaine administered using PF-72 was found in the pharmacodynamic study of prolonged analgesic effect. The results of this study indicated that local drug delivery by PF-72 hydrogel formulation may be an effective method to achieve extended relief of pain. Other advantages of ropivacaine administration using PF-72 include reduced systemic side effects and high localization of a drug in target tissues.

Vertebroplasty comparing injectable calcium phosphate cement compared with polymethylmethacrylate in a unique canine vertebral body large defect model.

BACKGROUND CONTEXT: Vertebroplasty was developed to mechanically reinforce weakened vertebral bodies. Polymethylmethacrylate (PMMA) bone cement has been most commonly used but carries risks of thermal injury and respiratory and cardiovascular complications. Calcium phosphate (CaP) offers the potential for biological resorption and replacement with new bone, restoring vertebral body mass and height. PURPOSE: To compare compressive strength, elastic modulus of the adjacent motion segments, and histologic response of vertebral bodies injected with either CaP or PMMA in a canine vertebroplasty model. STUDY DESIGN: By using a canine vertebroplasty model, two level vertebroplasties were performed at L1 and L3 and studied for 1 month (n=10) and 6 months (n=10). In each canine, one vertebral defect was randomly injected with either CaP cement (BoneSource; Stryker, Freiberg, Germany) or PMMA. METHODS: Twenty dogs had an iatrogenically created cavitary lesion at two nonadjacent levels injected with either CaP or PMMA. Canines from each group were tested mechanically (n=5) and histologically (n=5). Histology consisted of axial sections of the L1 and L3 vertebral bodies and high-resolution contact radiographs. Sections from each specimen were embedded in plastic without decalcification to study the bone-cement interface. Bone-cement interfaces were compared for evidence of necrosis, fibrosis, foreign body response, cement resorption, and new bone formation between the PMMA and CaP treatments groups. Mechanical compression testing was performed on specimens from the 1-month (n=5) and 6-month (n=5) time periods. The T13 vertebral body was used as an intact control for the destructive compression testing of L1 and L3. Each vertebral body was compressed to 50% of its original height under displacement control at 15 mm/min to simulate a nontraumatic loading situation. Force and displacement data were recorded in real time. RESULTS: Vertebral sites containing PMMA were characterized by a thin fibrous membrane. PMMA was detected within the trabeculae, vascular channels, and the spinal canal. Unlike PMMA, CaP underwent resorption and remodeling with vascular invasion and bone ingrowth. Woven and lamellar bone was found on the CaP cement surface, within the remodeled material, and on the surrounding trabeculae. Vertebral body compression strength testing revealed no significant difference in vertebral body height and compressive strength between PMMA and CaP. There was a trend for CaP-treated vertebrae to increase in compressive strength from 1 month to 6 months, whereas PMMA decreased compressive strength when compared with adjacent nontreated vertebrae. CONCLUSION: For both short and intermediate time periods, the injection of CaP cement can be an effective method to treat large vertebral defects. Early results indicate that CaP remodeling might result in the resorption of the majority of the cement with replacement by lamellar bone.

Biomechanical comparison of single- and dual-lead pedicle screws in cadaveric spine.

OBJECT: The pedicle screw (PS) is the cornerstone of spinal instrumentation, and its failure often entails additional surgery. Screw pullout is one of the most common reasons for screw failure, particularly in the elderly population. In this study the authors undertook a biomechanical comparison of the maximum pullout force (MPF) required for single- and dual-lead PSs in cadaver vertebrae. METHODS: Radiographs of 40 cadaveric vertebrae (T11-L5) were obtained, and bone mineral density (BMD) was measured in the lateral plane using dual-x-ray absorptiometry with a bone densitometer. One screw of each design was implanted for side-by-side comparison. Vertebrae were potted and mounted on an MTS test frame for accurate measurement of MPF. A total of 80 PSs were tested, 40 each of single- and dual-lead design types. RESULTS: The average MPF for dual-lead screws (533.89 +/- 285.7 N) was comparable to that of single-lead screws (524.90 +/- 311.6 N) (p = 0.3733). The BMD had a significant correlation with MPF for both dual-lead (r = 0.56413, p < 0.0001) and single-lead screws (r = 0.56327, p < 0.0001). CONCLUSIONS: Barring the effect of BMD, this in vitro biomechanical test showed no significant difference in MPF between single- and dual-lead PSs. Dual-lead PSs can be used to achieve a faster insertion time, without compromising pullout force.

Biomechanical function of a balloon nucleus pulposus replacement system: A human cadaveric spine study.

With recent advances in motion-sparing techniques in spine surgery, disc nucleus replacement (DNR) has been introduced as a viable method to restore the biomechanical functions of the spine. Several methods of DNR have been proposed in the literature. However, the risk of device migration or extrusion is a major issue that should be addressed for a successful DNR. DNR using a balloon nucleus (BN) filled with pressurized fluid may be capable of reducing such risks while preserving the advantages of DNR. The objective of this study was to investigate the biomechanical functionalities of the human cadaveric lumbar motion segments with a custom made BN filled with saline at internal fluid pressure of 0.3 or 0.6 MPa in terms of axial and rotational flexibilities of the L4-L5 motion segment. Axial flexibility was quantified by the axial displacement resulting from an axial compressive force of 400 N while the rotational flexibility by the range of motions determined as the rotational angles in response to a pure moment of 6.0 Nm in flexion, extension, and right- and left-lateral bending directions. These tests were performed successively on the motion segment in the following conditions: intact, post nucleotomy, implanting BN with 0.3 MPa, and BN with 0.6 MPa. The nucleotomy was found to significantly increase both the axial and rotational flexibilities while the implantation of the BN reduced the axial and rotational flexibilities to those of the intact segment. The axial and rotational flexibilities of the segment with the BN with 0.3 MPa were greater than those of the segment with the BN with 0.6 MPa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:167-173, 2018.

Stabilization of the lumbar spine by spinal muscle forces producing compressive follower loads: 3-dimensional computational study.

Axial compressive loads whose direction changes along the spinal curvature (so called compressive follower loads (CFLs)) was postulated as a normal physiological load in the lumbar spine in the literature. Computational analyses were conducted in this study using finite element and optimization models of the spinal system incorporating 244 fascicles of back muscles. It was feasible to find optimum solutions for spinal muscle forces generating CFLs in the lumbar spine in 3-D postures of neutral standing, flexion 40°, extension 10°, axial rotation 10°, or lateral bending 30°. FE analyses demonstrated that the lumbar spine can be in a stable condition not under all CFL generating muscle forces but under those producing CFLs along a curve parallel to the spinal curvature located in the vicinity of the base spinal curve constructed by connecting the geometrical centers of the vertebral bodies. It was also possible to estimate the stable range of the relative location of such CFL curve to the base spinal curve. These results suggest that the lumbar spine in various 3-D postures can be stabilized by spinal muscles that generate CFLs in the spine, which at least in part supports the hypothesis of CFLs as a physiological load in the lumbar spine. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3004-3012, 2018.

Ultrasound-Mediated Microbubble Destruction Suppresses Melanoma Tumor Growth.

Melanoma is one of the most aggressive types of cancer, and its incidence has increased rapidly in the past few decades. In this study, we investigated a novel treatment approach, the use of low-intensity ultrasound (2.3 W/cm2 at 1 MHz)-mediated Optison microbubble (MB) destruction (UMMD) to treat melanoma in a flank tumor model. The effect of UMMD was first evaluated in the melanoma cell line B16 F10 (B16) in vitro and then in mice inoculated with B16 cells. MB+B16 cells were exposed to US in vitro, resulting in significant cell death proportional to duty cycle (R2 = 0.74): approximately 30%, 50%, 80% and 80% cell death at 10%, 30%, 50% and 100% DC respectively. Direct implantation of tumors with MBs, followed by sonication, resulted in retarded tumor growth and improved survival (p = 0.0106). Immunohistochemical analyses confirmed the significant changes in expression of the cell proliferation marker Ki67 (p = 0.037) and a microtubule-associated protein 2 (p = 0.048) after US + MB treatment. These results suggest that UMMD could be used as a possible treatment approach in isolated melanoma and has the potential to translate to clinical trials.

In vitro biomechanical comparison of transpedicular versus translaminar C-2 screw fixation in C2-3 instrumentation.

OBJECT: In instrumentation of the upper cervical spine, placement of pedicle screws into C-2 is generally safe, although there is the potential for injury to the vertebral arteries. Owing to this risk, translaminar screws into C-2 have been used. The aim of this study was to compare the stability of the in vitro cadaveric spine using C-2 laminar compared with C-2 pedicle screws in C2-3 instrumentation. METHODS: Eight fresh frozen human cadaveric cervical spines (C1-6) were potted at C1-2 and C5-6. Pure moments in increments of 0.3 Nm to a maximum of 1.5 Nm were applied in flexion, extension, right and left lateral bending, and right and left axial rotation. Each specimen was tested sequentially in three modes: 1) intact; 2) C2 pedicle screw-C3 lateral mass fixation; and 3) C2 laminar screw-C3 lateral mass fixation. The sequence of fixation testing was randomized. Motion was tracked with reflective markers attached to C-2 and C-3. RESULTS: Spinal levels with instrumentation showed significantly less motion than the intact spine in all directions and with all loads greater than 0.3 Nm (p < 0.05). Although there was no significant difference between C2 pedicle screw-C3 lateral mass fixation and C2 laminar screw-C3 lateral mass fixation, generally the former type of fixation was associated with less motion than the latter. CONCLUSIONS: When pedicle screws in C-2 are contraindicated or inappropriate, laminar screws in C-2 offer a safe and acceptable option for posterior instrumentation.

Effect of lower two-level anterior cervical fusion on the superior adjacent level.

OBJECT: Symptomatic multisegment disease is most common at the C5-6 and C6-7 levels, and two-level anterior cervical discectomy and fusion (ACDF) is performed most often at these levels. Therefore, it may be clinically important to know whether a C5-7 fusion affects the superior C4-5 segment. A biomechanical study was carried out using cadaveric cervical spine specimens to determine the effect of lower two-level anterior cervical fusion on intradiscal pressure and segmental motion at the superior adjacent vertebral level. METHODS: Five cadaveric cervical spine specimens were used in this study. The specimens were stabilized at T-1 and loaded at C-3 to 15 degrees flexion, 10 degrees extension, and 10 degrees lateral bending before and after simulated two-level ACDF with plate placement at C5-7. Intradiscal pressure was recorded at the C4-5 level, and segmental motion was recorded from C-4 through C-7. Differences in mean intradiscal pressures were calculated and analyzed using a paired Student t-test. When the maximum calibrated intradiscal pressures were exceeded ("overshot") during measurements, data from the specimens involved were analyzed using the motion data with a Student t-test. Values for pressure and motion obtained before and after simulated ACDF were compared. RESULTS: During flexion, the mean intradiscal pressure changes (+/- standard deviations) in the pre- and post-ACDF measurements were 1275 (+/- 225) mm Hg and 2475 (+/- 75) mm Hg, respectively (p < 0.05). When the results of pre-ACDF testing were compared with post-ACDF results, no significant difference was found in the mean changes in the intradiscal pressure during extension and lateral bending. The maximum calibrated intradiscal pressures were exceeded during the post-ACDF testing in four specimens in extension, three in flexion, and two in lateral bending. Comparison of pre- and post-ACDF data for all five specimens revealed significant differences in motion and intradiscal pressure (p < 0.05) during flexion, significant differences in motion (p < 0.05) but not in intradiscal pressure during extension, and significant differences in intradiscal pressure changes (p < 0.05) but not in motion during lateral bending. CONCLUSIONS: Simulated C5-7 ACDF caused a significant increase in intradiscal pressure and segmental motion in the superior adjacent C4-5 level during physiological motion. The increased pressure and hypermobility might accelerate normal degenerative changes in the vertebral levels adjacent to the anterior cervical fusion.

Pelvic floor muscle contraction and abdominal hollowing during walking can selectively activate local trunk stabilizing muscles.

BACKGROUND: Trunk muscle exercises are widely performed, and many studies have been performed to examine their effects on low back pains. However, the effect of trunk muscles activations during walking with pelvic floor muscle contraction (PFMC) and abdominal hollowing (AH) has not been clarified. OBJECT: To investigate whether walking with PFMC and AH is more effective for promoting local trunk muscle activation than walking without PFMC and AH. METHODS: Twenty healthy men (28.9 ± 3.14 years, 177.2 ± 4.25 cm, 72.1 ± 6.39 kg, body mass index 22.78 ± 2.38 kg/m2) were participated in this study. Surface electrodes were attached over the multifidus (MF), lumbar erector spinae (LES), thoracic erector spinae (TES), transverse abdominus-internal oblique abdominals (TrA-IO), external oblique abdominals (EO), and rectus abdominus (RA). The amplitudes of electromyographic signals were measured during a normal walking with and without PFMC and AH. RESULT: PFMC and AH while walking was found to result in significant bilateral increases in the normalized maximum voluntary contraction (MVC) of MFs and TrA-IOs (p< 0.05). Ratios of local muscle activity to global muscle activities were increased while performing PFMC and AH during normal walking. Bilateral TrA-IO/EO activity ratios were significantly increased by PFMC and AH (p< 0.05). CONCLUSION: Performance of the PFMC and AH during walking resulted in significantly more recruitment of local trunk muscles. This study suggests that PFMC and AH during normal daily walking improves activation of muscles responsible for spinal dynamic stabilization and might be useful if integrated into low back disability and pain physical rehabilitation efforts.

Hydroxyapatite-coating of pedicle screws improves resistance against pull-out force in the osteoporotic canine lumbar spine model: a pilot study.

BACKGROUND CONTEXT: In patients with spinal osteoporosis, the early achievement and maintenance of a biological bond between the pedicle screw and bone is important to avoid screw loosening complications. There are few reports of in vivo investigations involving biomechanical and histological evaluations in the osteoporotic spine. PURPOSE: To evaluate the effect of hydroxyapatite (HA)-coating on the pedicle screw in the osteoporotic lumbar spine and to investigate the relationship between resistance against the screw pull-out force and bone mineral density (BMD) of the vertebral body. STUDY DESIGN/SETTING: Mechanical and pathological investigations in the lumbar spine. METHODS: Two 24-month-old female beagle dogs were fed a calcium-free dog chow for 6 months after ovariectomy (OVX). BMD (in g/cm2) was measured by dual energy X-ray absorptiometry at pre-OVX and 6 months after OVX. Pedicle screws were placed from L1 to L6 at 6 months after OVX. Twenty-four pure titanium cortical screws (Synthes, #401-114) were used as pedicle screws (Ti-PS). Of these, 12 screws had HA-coating (HA-PS). The HA-PS screws were inserted into the right pedicles and the Ti-PS were inserted into the left pedicles. Ten days after this procedure, the lumbar spines were removed en bloc for screw pull-out testing and histological evaluation. RESULTS: The mean BMD value of the lumbar vertebrae 6 months after the OVX was 0.549+/-0.087 g/cm2, which was significantly less than the pre-OVX mean BMD of 0.603+/-0.092 g/cm2 (p < 0.001). The mean resistance against the pull-out force for the HA-PS was significantly greater at 165.6+/-26.5N than in the Ti-PS (103.1+/-30.2N, p < .001). The histological sections in the HA-PS clearly revealed new bone bonding with the apatite coating but only fibrous tissue bonding in the Ti-PS. CONCLUSIONS: The results of this study showed that the resistance to the pull-out force of HA-PS is 1.6 times that of Ti-PS. Furthermore, HA-PS has superior biological bonding to the surrounding bone, as early as 10 days after surgery in this osteoporotic spine model. Thus, in patients with osteoporosis, coating of the pedicle screw with HA may provide better stability and bonding between the pedicle screw and bone in the early postoperative period.

Biomechanical studies of an artificial disc implant in the human cadaveric spine.

OBJECT: The authors compared the biomechanical performance of the human cadaveric spine implanted with a metallic ball-and-cup artificial disc at L4-5 with the spine's intact state and after anterior discectomy. METHODS: Seven human L2-S1 cadaveric spines were mounted on a biomechanical testing frame. Pure moments of 0, 1.5, 3.0, 4.5, and 6.0 Nm were applied to the spine at L-2 in six degrees of motion (flexion, extension, right and left lateral bending, and right and left axial rotation). The spines were tested in the intact state as well as after anterior L4-5 discectomy. The Maverick disc was implanted in the discectomy defect, and load testing was repeated. The artificial disc created greater rigidity for the spine than was present after discectomy, and the spine performed biomechanically in a manner comparable with the intact state. CONCLUSIONS: The results indicate that in an in vitro setting, this model of artificial disc stabilizes the spine after discectomy, restoring motion comparable with that of the intact state.

Comparison of EMG during passive stretching and shortening phases of each muscle for the investigation of parkinsonian rigidity.

The aim of this study was to test the hypothesis in the literature that torque resistance of parkinsonian rigidity is the difference between the independent contributions of stretched and shortened muscles. The hypothesis was tested using muscle-specific stretch-shortening (MSSS) EMG ratio in this study. Nineteen patients with idiopathic Parkinson's disease (PD) and 18 healthy subjects (the mean age comparable to that of patients) participated in this study. The EMG activity was measured in the four muscles involved in wrist joint movement, i.e. flexor carpi radialis, flexor carpi ulnaris, extensor carpi radialis and extensor carpi ulnaris. The passive flexion-extension movement with a range of ±30∘ was applied at wrist joint. Root mean squared (RMS) mean was calculated from the envelope of the EMG for each of stretching and shortening phases. MSSS EMG ratio was defined as the ratio of RMS EMG of stretching phase and RMS EMG of shortening phase of a single muscle, and it was calculated for each muscle. MSSS EMG ratios were smaller than one in all muscles. These results indicate that all wrist muscles generate greater mean EMG during shortening than during stretching. Therefore, the torque resistance of parkinsonian rigidity cannot be explained as the simple summation of independent antagonistic torque pair.

Regression models for the quantification of Parkinsonian bradykinesia.

The aim of this study was to develop regression models for the quantification of parkinsonian bradykinesia. Forty patients with Parkinson's disease participated in this study. Angular velocity was measured using gyro sensor during finger tapping, forearm-rotation, and toe tapping tasks and the severity of bradykinesia was rated by two independent neurologists. Various characteristic variables were derived from the sensor signal. Stepwise multiple linear regression analysis was performed to develop models predicting the bradykinesia score with the characteristic variables as input. To evaluate the ability of the regression models to discriminate different bradykinesia scores, ANOVA and post hoc test were performed. Major determinants of the bradykinesia score differed among clinical tasks and between raters. The regression models were better than any single characteristic variable in terms of the ability to differentiate bradykinesia scores. Specifically, the regression models could differentiate all pairs of the bradykinesia scores (p<0.05) except for one pair in the finger tapping task and one pair in the toe tapping task. In contrast, any single characteristic variable was found not sensitive enough to discriminate many of the pairs, especially in case of the toe tapping task. The results suggest that the multiple regression models reflecting these differences would be beneficial for the quantification of bradykinesia because the cardinal features included in the determination of bradykinesia score differ among tasks as well as among the raters.

Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats.

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 µL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 µL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 µL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 µL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 µL had a significant analgesic effect for 2 days, even though T-gel at 50 µL further reduced the weight load, demonstrating that intra-articular T-gel (20 µL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting.