Can prophylactic C4/5 foraminotomy prevent C5 palsy after cervical laminoplasty with and without posterior instrumented fusion with maximal expansion?

OBJECTIVE: To prospectively examine whether laminoplasty with maximal expansion induces C5 palsy, even with prophylactic bilateral C4/5 foraminotomy. METHODS: Thirty-five consecutive patients with cervical myelopathy underwent laminoplasty (n = 19: LP group) or posterior decompression and fusion (n = 16: PDF group) with maximal expansion. Prophylactic bilateral C4/5 foraminotomy was performed alternately in consecutive five patients undergoing each type of surgery. In each type of surgery, the first and third consecutive five patients did not undergo foraminotomy (NF subgroup: 20 patients), while the second and fourth consecutive five patients underwent foraminotomy (F subgroup: 15 patients). The widths between the gutters was equivalent to the diameter of the spinal canal, and an inclination angle of the lamina of approximately 90° was created during laminoplasty. The incidence and severity of postoperative C5 palsy were investigated. Patients with a manual muscle testing score for the deltoid muscle and/or biceps brachii muscle of ≤ 2 were diagnosed with severe palsy. RESULTS: The respective incidences of C5 palsy in the F and NF subgroups were 33% and 20% in the LP group and 50% and 20% in the PDF group. Severe palsy occurred in 67% and 0% of patients who had developed palsy in F and NF subgroups, respectively, in the LP group, and in 100% of patients in the PDF group. Furthermore, 40% of the patients with severe palsy took more than 6 months to recover. CONCLUSIONS: Laminoplasty with maximal expansion induced C5 palsy in both the LP and PDF groups, even with the addition of prophylactic bilateral C4/5 foraminotomy.

A novel method for evaluating activity of transient receptor potential channels using a cellular dielectric spectroscopy.

Cellular dielectric spectroscopy (CDS) is a novel technology enabling pharmacological evaluation of multiple receptor types with a label-free cell-based assay. We evaluated activities of a family of ligand-gated channels, transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels by an electrical impedance-based biosensor (CellKey™ system) using CDS. Measures of both potency (EC50) and efficacy (Emax) of these agonists with CellKey™ were almost identical to those made using the traditional Ca2+ influx assay in TRPV1- or TRPA1-expressing cells, suggesting that CellKey™ is a simpler and easier means of evaluating TRP activities.

Improvement in the results of the simple-foot-tapping test and cross-sectional area of the dural sac in patients with C5 palsy after posterior cervical spine surgery.

INTRODUCTION: The smaller cross-sectional areas of the dural sacs in patients without C5 palsy after posterior cervical spine surgery may lead to less neurological improvement. OBJECTIVES: The aim of this retrospective study was to clarify the differences in the cross-sectional area of the dural sac in the cervical spine and neurological improvement in patients with and without C5 palsy after posterior cervical spinal surgery. METHODS: We retrospectively evaluated the postoperative cross-sectional areas of the dural sacs and neurological outcomes in patients with and without C5 palsy after posterior cervical spine surgery. We compared the postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 on magnetic resonance images between the C5 palsy group (n = 19) and the no-C5 palsy group (n = 84) after posterior cervical spinal surgery 1 year postoperatively. Performance tests, namely, the 10-s grip-and-release test and the 10-s single-foot-tapping (FT) test, were compared between the two groups. RESULTS: Postoperative cross-sectional areas of the dural sac at C4/5 and C5/6 (233.3 mm2 and 226.6 mm2, respectively) in the C5 palsy group were significantly larger (P = 0.0036 and P = 0.0039, respectively) than those (195.0 mm2 and 193.8 mm2, respectively) in the no-C5 palsy group. Postoperative gain in the grip-and-release test was similar between the two groups. Postoperative gain in the FT test (4.9 times) in the C5 palsy group was significantly larger (P = 0.0060) than that (1.8 times) in the no-C5 palsy group. CONCLUSIONS: In the C5 palsy group 1 year after posterior cervical spine surgery, the cross-sectional areas of the dural sac were larger, and the 10-s single FT test improved noticeably.

Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways.

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

A novel posterior approach preserving three muscles inserted at C2 in multilevel cervical posterior decompression and fusion using C2 pedicle screws.

PURPOSE: To present a novel posterior approach in multilevel cervical posterior decompression and fusion (PDF) using C2 pedicle screws that preserves the rectus capitis posterior major, oblique capitis inferior, and semispinalis cervicis. METHODS: We analyzed 30 consecutive patients who underwent C2-T1 PDF using an approach that preserved these three muscles without resecting. We assessed O-C2 range of motion (ROM), cross-sectional area of the cervical posterior muscles, rotational ROM, visual analog scale (VAS) for axial pain, neck disability index (NDI), and limitations of activities of daily living (ADL) involving neck movements. RESULTS: Mean preoperative O-C2 ROM (23.6°) was significantly increased postoperatively (33.0°). Mean atrophy rate of the cross-sectional area was 3.9%. Postoperatively, 69.8% of the preoperative rotational ROM (113.3°) was retained. The preoperative VAS for axial pain and the NDI did not increase postoperatively. The postoperative O-C2 ROM (33.9°) in 26 patients for whom extension ADL were possible was significantly larger than that in four patients for whom extension ADL were impossible (26.9°). The postoperative retained rate of rotational ROM (75.8%) in 18 patients for whom rotation ADL were possible was significantly larger than that in 12 patients for whom rotation ADL were impossible (62.3%). CONCLUSIONS: This is potentially an effective approach for maintaining O-C2 ROM and rotational ROM, which enabled good levels of ADL after C2-T1 PDF. Axial pain and NDI were not worse after PDF.

New diagnostic support tool for patients with leg symptoms caused by lumbar spinal stenosis and lumbar intervertebral disc herniation: A self-administered, self-reported history questionnaire.

BACKGROUND: There are no diagnostic support tools composed of a simple, single-sheet, self-administered, self-reported history questionnaire (SSHQ) for patients with leg symptoms caused by either lumbar spinal stenosis (LSS) or lumbar disc herniation (LDH), at the same time, can discriminate the two diseases. METHODS: We conducted retrospective and prospective derivation studies and a prospective validation study. Based on data from 137 patients with LSS and 206 with LDH, we identified key prediction factors to establish the diagnosis of LSS and LDH, which became the basis of a temporary SSHQ. Next, we performed a prospective derivation study in which 296 patients with LSS or LDH completed preoperatively this temporary SSHQ. After univariate and multivariate analyses of each question, questions on both diseases in addition to age factor were selected, providing the final version of the SSHQ. A validation study was subsequently performed with 342 consecutive patients with leg symptoms. The sensitivity, specificity and likelihood ratio of this SSHQ were calculated to determine the cut-off points for LSS and LDH. RESULTS: A SSHQ with 15 questions was developed from retrospective and prospective derivation studies. The score of each question was weighted based on the multivariate analysis and then, it was approximated to integer value. According to assessment of the discriminatory performance of the clinical prediction rule of the SSHQ, the cut-off point for LSS was ≥13 and that for LDH was ≥11. The sensitivity, specificity, and positive and negative likelihood ratios of this SSHQ at those cut-off points were, respectively, 92.7%, 84.7%, 6.07, and 0.09 for LSS, and 91.0%, 85.2%, 6.15, and 0.11 for LDH. CONCLUSIONS: This is the first report of a diagnostic support tool for patients with LSS- or LDH-induced leg symptoms combined in a single SSHQ that could help establish diagnosis of the two diseases in the daily clinical practice.

Tramadol and its metabolite m1 selectively suppress transient receptor potential ankyrin 1 activity, but not transient receptor potential vanilloid 1 activity.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice. Reportedly, tramadol and its metabolite (M1) bind to µ-opioid receptors and/or inhibit reuptake of monoamines in the central nervous system, resulting in the activation of the descending inhibitory system. However, the fundamental mechanisms of tramadol in pain control remain unclear. TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively. METHODS: We examined whether and how tramadol and M1 act on human embryonic kidney 293 (HEK293) cells expressing human TRPV1 (hTRPV1) or hTRPA1 by using a Ca imaging assay and whole-cell patch-clamp recording. RESULTS: Tramadol and M1 (0.01-10 µM) alone did not increase in intracellular Ca concentration ([Ca]i) in HEK293 cells expressing hTRPV1 or hTRPA1 compared with capsaicin (a TRPV1 agonist) or the allyl isothiocyanate (AITC, a TRPA1 agonist), respectively. Furthermore, in HEK293 cells expressing hTRPV1, pretreatment with tramadol or M1 for 5 minutes did not change the increase in [Ca]i induced by capsaicin. Conversely, pretreatment with tramadol (0.1-10 µM) and M1 (1-10 µM) significantly suppressed the AITC-induced [Ca]i increases in HEK293 cells expressing hTRPA1. In addition, the patch-clamp study showed that pretreatment with tramadol and M1 (10 µM) decreased the inward currents induced by AITC. CONCLUSIONS: These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1, and that hTRPA1 may play a role in the analgesic effects of these compounds.

Can MRI predict subsequent pseudarthrosis resulting from osteoporotic thoracolumbar vertebral fractures?

PURPOSE: The purpose of this study was to assess the ability of short inversion time inversion-recovery (STIR) in magnetic resonance imaging for predicting the prognosis of osteoporotic vertebral fractures. METHODS: We analyzed 63 vertebrae of 56 patients who had osteoporotic vertebral fracture (Th10-L2) prospectively. Image finding of a homogeneous high signal change on a fractured vertebra was evaluated and all vertebrae were divided into "homogenous high signal change group" or "non-homogenous high signal change group". On the other hand, image finding of linear black signal area was evaluated and all vertebrae were divided into "linear black signal area group" or "non-linear black signal area group". RESULTS: Sixteen and 24 vertebrae were included in the homogenous high signal change group or the linear black signal area group, respectively. The 16 homogenous high signal change cases did not result in non-union, and 47 non-homogenous high signal change cases resulted in 14 non-unions, a significant difference. Twenty-four linear black signal area and 39 non-linear black signal area cases resulted in 10, and 4 non-unions, respectively, also a significant difference. The kyphosis progression rate of the linear black signal area group (mean 35%) was significantly higher than that of non-linear black signal area group (mean 23%). The visual analog scale of back pain of the linear black signal area group (mean 35 mm) was significantly higher than that of the non-linear black signal area group (mean 23 mm). CONCLUSIONS: STIR was useful for predicting bone union, kyphosis, and back pain in patients with osteoporotic vertebral fracture.

Prevalence and symptom of ossification of posterior longitudinal ligaments in the Japanese general population.

BACKGROUND: Ossification of the posterior longitudinal ligaments (OPLL) causes myelopathy with progression or trauma. Most OPLL patients visit the hospital after severe symptoms occur, and surgery did not supply complete relief in severe symptoms related to OPLL. While it is necessary to diagnose OPLL early and observe carefully, the nature of symptoms and asymptomatic OPLL have been unclear. The purposes of this study were to investigate the prevalence and symptoms of ossification of the posterior longitudinal ligaments (OPLL) of the cervical spine in the general population. METHODS: The subjects were 1291 Japanese general residents. Radiographic OPLL was detected by lateral view of the cervical spine, and subjects were classified into OPLL and non-OPLL groups. Visual analog scales of neck stiffness, neck pain, arm pain, and the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire were examined. Neck and arm symptoms were compared among the presence of OPLL, and among subtypes (continuous, segmental, and mixed types) statistically. RESULTS: Prevalence of OPLL was 3.7 % in overall participants, 3.9 % in symptomatic participants, and 2.2 % in asymptomatic participants. While 86.7 % of participants with OPLL had symptoms, the consultation rate was only 6.7 %. The female OPLL group had higher neck pain than the non-OPLL group, and neck function of JOACMEQ in the continuous type of OPLL was significantly restricted compared to those without OPLL and with the mixed type of OPLL. CONCLUSIONS: Prevalence of OPLL was 3.7 %, and most of them had neck and arm symptoms; however, they did not visit hospitals. Asymptomatic OPLL had the potential risk for spinal cord injury and myelopathy. Early detection and careful observation would prevent the severe symptoms induced by OPLL.

Interobserver and intraobserver reliability of the classification and diagnosis for ossification of the posterior longitudinal ligament of the cervical spine.

PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine has been classified into four types by lateral plain radiographs, but the reliability of the classification and of the diagnosis of either cervical OPLL or cervical spondylotic myelopathy (CSM) was unknown. We investigated the interobserver and intraobserver reliability of the classification and diagnosis for OPLL by radiographs and computed tomography (CT) images. METHODS: A total of 16 observers classified each patient's images into five groups; OPLL continuous, segmental, mixed, circumscribed type, or CSM. To evaluate interobserver reliability, the observers first classified only radiograph images, and next both radiographs and CT images. On another day they followed the same procedure to evaluate intraobserver reliability. We also evaluated interobserver and intraobserver reliability of the diagnosis of either cervical OPLL or CSM. RESULTS: Interobserver reliability of the classification with radiographs only showed moderate agreement, but interobserver reliability with both radiographs and CT images showed substantial agreement. Intraobserver of reliability the classification was also improved by additional CT images. Interobserver reliability of the diagnosis with both radiographs and CT images was almost similar to with radiographs only. Intraobserver reliability of the diagnosis was improved by additional CT images. CONCLUSIONS: This study suggested that the reliability of the classification and diagnosis for cervical OPLL was improved by additional CT images. We propose that diagnostic criteria for OPLL include both radiographs and CT images.

Novel motion preservation device for atlantoaxial instability.

STUDY DESIGN: An in vitro cadaveric biomechanical study. OBJECTIVE: To evaluate the anteroposterior (A-P) stability and the flexibility of our novel motion preservation device (MPD) using cadaveric cervical spines. SUMMARY OF BACKGROUND DATA: The MPD intended to restrict the A-P instability of the C1-C2 complex and to preserve the axial rotation, flexion, extension, and lateral bending was designed and produced. The stability and the flexibility of the MPD was evaluated. METHODS: Ten embalmed cadaveric specimens were loaded with pure A-P translation force and the A-P translational distances were measured. Each specimen was tested for the following 4 models, respectively: Intact (control), the Dens-removed, the MPD instrumented, and a Rod fixation system instrumented. Fifteen specimens were loaded with pure moments (up to 1.5 Nm), and the C1-C2 range of motion (ROM) was measured for flexion, extension, lateral bending, and axial rotation using a stereophotogrammetry motion analysis system. RESULTS: Mean A-P translational distances were 4.26 mm in Intact, 13.1 in the Dens-removed, 5.42 in the MPD, and 2.58 in the Rod fixation. The distance values with the MPD had no significant difference compared with Intact. Mean C1-C2 ROM of Intact, the MPD, and the Rod fixation at 1.5 Nm were: 14.7, 6.96, and 2.11 degrees in flexion, 6.46, 4.72, and 2.84 degrees in extension, 3.29, 4.02, and 1.01 degrees in right lateral bending, 4.92, 4.58, and 1.84 degrees in left lateral bending, 26.4, 15.4, and 1.16 degrees in right axial rotation, and 25.6, 14.3, and 1.21 degrees in left axial rotation, respectively. CONCLUSIONS: The MPD restricted the A-P instability of the C1-C2 complex. In flexion, extension, and axial rotation, the C1-C2 ROM of the MPD was about 50% of the ROM in Intact, whereas equivalent to Intact in lateral bending.

New Grading System for Cervical Paraspinal Soft Tissue Damage After Traumatic Cervical Spinal Cord Injury Without Major Fracture Based on the Short-T1 Inversion Recovery Mid-Sagittal MRI for Prediction of Neurological Improvements: The STIR-MRI Grade.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop a grading method for cervical paraspinal soft tissue damage after cervical spinal cord injury (CSCI) without major fracture based on the short T1 inversion recovery (STIR) mid-sagittal magnetic resonance image (MRI) for prediction of neurological improvements. METHODS: This study included 34 patients with CSCI without major fracture, treated conservatively for at least 1 year and graded using the STIR-MRI Grade. This system consists of anterior grades; A0: no high-intensity area (HIA), A1: linear HIA, and A2: fusiform HIA, and posterior grades; P0: no HIA, P1: HIA not exceeding the nuchal ligament, and P2: HIA exceeding the nuchal ligament, within 24 hours postinjury. The American Spinal Injury Association impairment scale (AIS) and the Japanese Orthopedic Association (JOA) scores were examined. RESULTS: Anterior grades were not significantly correlated with the AIS and JOA score. At both injury and final follow-up, the AIS in P2 patients was significantly more severe (P = 0.007, P = 0.015, respectively) than that in P0 patients. At the injury, the AIS in P2 patients was significantly more severe (P = 0.008) than that in P1 patients. Among P2 patients only, the JOA score at the injury (1.4 points) did not improve by the final follow-up (3.9 points). The final follow-up JOA score (3.9 points) in P2 patients was significantly lower than that (13.6 points) in P0 patients (P = 0.016). CONCLUSIONS: Grade P2 led to poor neurological outcomes. The STIR-MRI Grade is a prognostic indicator for neurological improvements past-CSCI.

Prevalence of Cervical Canal Stenosis in Patients with Femoral Fracture: A Retrospective Single-Center Study.

Introduction: Cervical spine surgery reduces falls and subsequent femoral fractures. Nonetheless, current evidence on the prevalence of cervical cord compression (CCC) and increased signal intensity (ISI) in patients with femoral fractures is limited. We aimed to determine the prevalence of CCC and ISI and characterize the physical status and imaging findings using cervical spine magnetic resonance imaging (MRI) and brain computed tomography (CT) in patients with femoral fractures. Methods: This study included 173 patients (140 women, 33 men) with femoral fractures caused by falling, who underwent both cervical spine MRI and brain CT. CCC cases classified as grade 2 (compression of less than one-third of the spinal cord) or higher were investigated. The ISI of the severely affected intervertebral disc level was evaluated using T2-weighted MRI. Hand grip strength and myelopathic signs were also evaluated. Data analysis was performed using the χ2 test, Fisher's exact test, and Student's t-test. Results: Among the 173 patients, 83 (48.0%) had CCC, 29 (16.8%) had ISI, and 68 (39.3%) had abnormal brain CT findings. There was no ISI in patients in the non-CCC group. The patients' average age in the CCC group was significantly higher than that in the non-CCC group. There was no significant difference in the proportion of myelopathic sign and abnormal brain CT findings between the CCC and non-CCC groups or between the ISI and non-ISI groups. Bilateral hand grip strength was significantly negatively correlated with the stenosis rate (right, p=0.047; left, p=0.0018). Conclusions: In conclusion, our study showed that patients with femoral fractures had a high frequency of cervical canal stenosis and intracranial lesions using cervical spine MRI and brain CT.

The effect of disruption of the repaired nuchal ligament on clinical outcomes after posterior cervical spine surgery: A retrospective comparative study.

OBJECTIVE: This study aimed to investigate whether disruption of the repaired nuchal ligament (NL) affects clinical outcomes following posterior cervical spine surgery. METHODS: This retrospective study included 101 patients (65 males, 36 females) who underwent posterior cervical spine surgery, 69 of whom received laminoplasty (LP), and 32 posterior decompression and fusion (PDF). The NL was split during the surgical approach and repaired at the time of wound closure. The frequency and spinal levels of NL disruption at one month, six months, and one year postoperatively were evaluated on mid-sagittal and axial magnetic resonance images. Postoperative axial symptoms, Neck Disability Index, T1 slope, flexion and extension angle, C2-C7 lordotic angle, and decrease rate of C2-C7 range of motion (ROM) were examined at six months and/or one year postoperatively. Based on the NL disruption levels, the patients were divided into the upper group (C2-C5), lower group (C6-T1), and non-disruption group. RESULTS: Although the lower group contained patients with NL disruption (10%) after LP at final follow-up, all PDF patients belonged to the non-disruption group. For the LP patients, the postoperative axial symptoms, Neck Disability Index, T1 slope, flexion and extension angle, and C2-C7 lordotic angle did not significantly differ between the lower and non-disruption groups; however, the rate of C2-C7 ROM decrease in the lower group (48%) was considerably larger than that in the non-disruption group (33%) after LP. CONCLUSION: Evidence from this study has shown that postoperative disruption of the repaired NL has no significant effect on postoperative axial symptoms and C2-C7 alignment, but it can affect the rate of decrease in C2-C7 ROM after LP. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

TRPV1 gene deficiency attenuates miniature EPSC potentiation induced by mannitol and angiotensin II in supraoptic magnocellular neurons.

The release of arginine vasopressin (AVP) from the magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) is crucial for body fluid homeostasis. The MNC activity is modulated by synaptic inputs and humoral factors. A recent study demonstrated that an N-terminal splice variant of the transient receptor potential vanilloid type 1 (TRPV1) is essential for osmosensory transduction in the SON. In the present study, we examined the effects of mannitol and angiotensin II on miniature EPSCs (mEPSCs) in the supraoptic MNCs using whole-cell patch-clamp recording in in vitro slice preparation. Mannitol (60 mm) and angiotensin II (0.1 microm) increased the frequency of mEPSCs without affecting the amplitude. These effects were attenuated by pre-exposure to a nonspecific TRPV channel blocker, ruthenium red (10 microm) and enhanced by pre-exposure to cannabinoid type1 receptor antagonist, AM251 (2 microm). Mannitol-induced potentiation of mEPSCs was not attenuated by angiotensin II receptor antagonist, losartan (10 microm), indicating independent pathways of mannitol and angiotensin II to the TRPV channels. The potentiation of mEPSCs by mannitol was not mimicked by a TRPV1 agonist, capsaicin, and also not attenuated by TRPV1 blockers, capsazepine (10 microm). PKC was involved in angiotensin II-induced potentiation of mEPSCs. The effects of mannitol and angiotensin II on the supraoptic MNCs in trpv1 knock-out mice were significantly attenuated compared with those in wild-type mice counterparts. The results suggest that hyperosmotic stimulation and angiotensin II independently modulate mEPSCs through capsaicin-insensitive TRPV1 channel in the presynaptic terminals of the SON.

The tramadol metabolite O-desmethyl tramadol inhibits substance P-receptor functions expressed in Xenopus oocytes.

Tramadol has been widely used as analgesic. O-Desmethyl tramadol (ODT) is one of the main metabolites of tramadol, having much greater analgesic potency than tramadol itself. Substance P receptors (SPR) are well known to modulate nociceptive transmission within the spinal cord. In this study, we investigated the effects of ODT on SPR expressed in Xenopus oocytes by examining SP-induced Ca(2+)-activated Cl(-) currents. ODT inhibited the SPR-induced Cl(-) currents at pharmacologically relevant concentrations. The protein kinase C (PKC) inhibitor bisindolylmaleimide I did not abolish the inhibitory effects of ODT on SP-induced Ca(2+)-activated Cl(-) currents. The results suggest that the tramadol metabolite ODT inhibits the SPR functions, which may be independent of activation of PKC-mediated pathways.

Sevoflurane inhibits the µ-opioid receptor function expressed in Xenopus oocytes.

Sevoflurane is widely used for anesthesia, and is commonly used together with opioids in clinical practice. However, the effects of sevoflurane on µ-opioid receptor (µOR) functions is still unclear. In this study, the effects of sevoflurane on µOR functions were analyzed by using Xenopus oocytes expressing a µOR fused to chimeric Gα protein G(qi5) (µOR-G(qi5)). Sevoflurane by itself did not elicit any currents in oocytes expressing µOR-G(qi5), whereas sevoflurane inhibited the [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO)-induced Cl(-) currents at clinically used concentrations. Sevoflurane did not affect the Cl(-) currents induced by AlF(4)(-), which directly led to activation of G proteins. The inhibitory effects of sevoflurane on the DAMGO-induced currents were not observed in oocytes pretreated with the protein kinase C (PKC) inhibitor GF109203X. These findings suggest that sevoflurane would inhibit µOR function. Further, the mechanism of inhibition by sevoflurane would be mediated by PKC.

Perioperative cardiopulmonary complications after cervical spine surgery in the prone position: the relationship between age and preoperative testing.

BACKGROUND: Cardiac arrest during spine surgery in the prone position is difficult to manage as poor access makes cardiopulmonary resuscitation and defibrillation difficult. Advanced age is the maximal risk factor for cardiac arrest. Therefore, we wanted to determine the relationship between age and cardiac risk factors/pre-operating tests for cervical spine surgery in the prone position. METHODS: The inclusion criteria for this study specified 88 patients scheduled should undergo cervical spine surgery in the prone position. The patients were divided into two groups: Paients in group A (50 patients) were aged 69 and under, Group B (38 patients) 70 and above. All patients responded to a medical interview about eight cardiac risk factors including past history, chest symptoms, diabetes mellitus, hypertension, hyperlipidemia, obesity, smoking, and family history. All patients underwent physical examination and 24-h Holter ECG and echocardiography performed by two cardiologists before surgery. We analyzed relationships between cardiac risk factors and ECG/echocardiography and investigated intra- and postoperative cardiovascular complications. RESULTS: Although there were no significant differences in the number of cardiac risk factors between the two groups, the frequency of hypertension was significantly greater in Group B than in Group A. The frequency of abnormal ECG and echocardiography findings especially was significantly greater in Group B than in Group A. In ECG and echocardiography, three patients in Group B who had no cardiac risk factors before surgery showed abnormal findings, and one of the three patients had the amalgamation of arrhythmia after the operation. Also, in Group B, cardiovascular complications occurred in one case during operation. CONCLUSION: These results suggested that patients aged 70 and above should undergo ECG and echocardiography examination before cervical spine surgery in the prone position whether they have cardiac risk factors or not . A prospective, randomized multi-center study with a larger patient sample is warranted to ultimately demonstrate how patients should be tested before spine surgery in the prone position.

Effects of sevoflurane on voltage-gated sodium channel Na(v)1.8, Na(v)1.7, and Na(v)1.4 expressed in Xenopus oocytes.

Sevoflurane is widely used as a volatile anesthetic in clinical practice. However, its mechanism is still unclear. Recently, it has been reported that voltage-gated sodium channels have important roles in anesthetic mechanisms. Much attention has been paid to the effects of sevoflurane on voltage-dependent sodium channels. To elucidate this, we examined the effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 expressed in Xenopus oocytes. The effects of sevoflurane on Na(v) 1.8, Na(v) 1.4, and Na(v) 1.7 sodium channels were studied by an electrophysiology method using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Sevoflurane at 1.0 mM inhibited the voltage-gated sodium channels Na(v)1.8, Na(v)1.4, and Na(v)1.7, but sevoflurane (0.5 mM) had little effect. This inhibitory effect of 1 mM sevoflurane was completely abolished by pretreatment with protein kinase C (PKC) inhibitor, bisindolylmaleimide I. Sevoflurane appears to have inhibitory effects on Na(v)1.8, Na(v)1.4, and Na(v) 1.7 by PKC pathways. However, these sodium channels might not be related to the clinical anesthetic effects of sevoflurane.

Critical points and effectiveness of prophylactic C4/5 foraminotomy to prevent C5 palsy after posterior cervical spine surgery.

OBJECTIVE: The aim of this study was to clarify the cut-off values of the spinal canal parameters as risk factors for C5 palsy after posterior cervical spine surgery with and without foraminotomy. METHODS: One hundred three consecutive patients (67 males, 36 females; mean age = 66 years, age range = 27-87 years) with cervical myelopathy who underwent posterior cervical spine surgery at our institution were retrospectively reviewed and included in the study. The first consecutive 69 patients who underwent posterior cervical spine surgery with prophylactic bilateral C4/5 foraminotomy were designated as the F (+) group. The subsequent 34 consecutive patients who underwent posterior cervical spine surgery without prophylactic bilateral C4/5 foraminotomy were designated as the F (-) group. All patients were then divided into four subgroups. In the F (+) group, patients with C5 palsy were designated as the F (+) P (+) subgroup (n = 13), while those without C5 palsy were designated as the F (+) P (-) subgroup (n = 56). In the F (-) group, patients with C5 palsy were designated as the F (-) P (+) subgroup (n = 5), while those without C5 palsy were designated as the F (-)P(-) subgroup (n = 29). Receiver operating characteristic curves were used to investigate the cut-off values of the spinal canal parameters for the development of postoperative C5 palsy. The assessed spinal parameters were the gutter positions (GP), laminar inclination angles (LIA), and postoperative cross-sectional areas (CSA) of the dural sac. The risk ratios (RR) of the spinal canal parameters as risk factors for C5 palsy were evaluated. RESULTS: The incidence of C5 palsy was similar between the F (+) group (18.8%) and the F (-) group (14.7%). The cut-off values for each spinal canal parameter in the F (+) group (GP: 0.82-0.84, LIA: 58.9-62.4°, and CSA: 189.5-200 mm2 ) were similar to those in the F (-) group (0.81-0.89, 61.7-62.5°, and 197.5-199.5 mm2, respectively). In the RR results for C5 palsy, the LIA was highest in both groups. The F (+) P (-) subgroup had significantly larger mean CSA at C4/5 and C5/6 (202.3 mm2 and 200.9 mm2, respectively) than the F (-)P(-) subgroup (177.3 mm2 and 178.9 mm2, respectively) (P = 0.0181 and P = 0.0277, respectively). Prophylactic C4/5 foraminotomy did not specifically prevent postoperative C5 palsy due to foraminal stenosis at C4/5. CONCLUSION: C4/5 foraminotomy should not be recommended for avoidance of C5 palsy. Although the bony spinal parameters were similar between the F (+) and F (-) groups, the CSA in the F (+) group was significantly than that in the F (-) group in the patients without C5 palsy.