Pharmacogenetic inhibition of lumbosacral sensory neurons alleviates visceral hypersensitivity in a mouse model of chronic pelvic pain.

The study investigated the cellular and molecular mechanisms in the peripheral nervous system (PNS) underlying the symptoms of urologic chronic pelvic pain syndrome (UCPPS) in mice. This work also aimed to test the feasibility of reversing peripheral sensitization in vivo in alleviating UCPPS symptoms. Intravesical instillation of vascular endothelial growth factor A (VEGFA) was used to induce UCPPS-like symptoms in mice. Spontaneous voiding spot assays and manual Von Frey tests were used to evaluate the severity of lower urinary tract symptoms (LUTS) and visceral hypersensitivity in VEGFA-instilled mice. Bladder smooth muscle strip contractility recordings (BSMSC) were used to identify the potential changes in myogenic and neurogenic detrusor muscle contractility at the tissue-level. Quantitative real-time PCR (qPCR) and fluorescent immunohistochemistry were performed to compare the expression levels of VEGF receptors and nociceptors in lumbosacral dorsal root ganglia (DRG) between VEGFA-instilled mice and saline-instilled controls. To manipulate primary afferent activity, Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADD) were expressed in lumbosacral DRG neurons of TRPV1-Cre-ZGreen mice via targeted adeno-associated viral vector (AAVs) injections. A small molecule agonist of Gi-DREADD, clozapine-N-oxide (CNO), was injected into the peritoneum (i. p.) in awake animals to silence TRPV1 expressing sensory neurons in vivo during physiological and behavioral recordings of bladder function. Intravesical instillation of VEGFA in the urinary bladders increased visceral mechanical sensitivity and enhanced RTX-sensitive detrusor contractility. Sex differences were identified in the baseline detrusor contractility responses and VEGF-induced visceral hypersensitivity. VEGFA instillations in the urinary bladder led to significant increases in the mRNA and protein expression of transient receptor potential cation channel subfamily A member 1 (TRPA1) in lumbosacral DRG, whereas the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1) and VEGF receptors (VEGFR1 and VEGFR2) remained unchanged when compared to saline-instilled animals. Importantly, the VEGFA-induced visceral hypersensitivity was reversed by Gi-DREADD-mediated neuronal silencing in lumbosacral sensory neurons. Activation of bladder VEGF signaling causes sensory neural plasticity and visceral hypersensitivity in mice, confirming its role of an UCPPS biomarker as identified by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) research studies. Pharmacogenetic inhibition of lumbosacral sensory neurons in vivo completely reversed VEGFA-induced pelvic hypersensitivity in mice, suggesting the strong therapeutic potential for decreasing primary afferent activity in the treatment of pain severity in UCPPS patients.

Thoracolumbar interfascial plane block for postoperative analgesia in spine surgery: A systematic review and meta-analysis.

INTRODUCTION: Thoracolumbar interfascial plane (TLIP) block has been discussed widely in spine surgery. The aim of our study is to evaluate analgesic efficacy and safety of TLIP block in spine surgery. METHOD: We performed a quantitative systematic review. Randomized controlled trials that compared TLIP block to non-block care or wound infiltration for patients undergoing spine surgery and took the pain or morphine consumption as a primary or secondary outcome were included. The primary outcome was cumulative opioid consumption during 0-24-hour. Secondary outcomes included postoperative pain intensity, rescue analgesia requirement, and adverse events. RESULT: 9 randomized controlled trials with 539 patients were included for analysis. Compared with non-block care, TLIP block was effective to decrease the opioid consumption (WMD -16.00; 95%CI -19.19, -12.81; p<0.001; I2 = 71.6%) for the first 24 hours after the surgery. TLIP block significantly reduced postoperative pain intensity at rest or movement at various time points compared with non-block care, and reduced rescue analgesia requirement ((RR 0.47; 95%CI 0.30, 0.74; p = 0.001; I2 = 0.0%) and postoperative nausea and vomiting (RR 0.58; 95%CI 0.39, 0.86; p = 0.006; I2 = 25.1%). Besides, TLIP block is superior to wound infiltration in terms of opioid consumption (WMD -17.23, 95%CI -21.62, -12.86; p<0.001; I2 = 63.8%), and the postoperative pain intensity at rest was comparable between TLIP block and wound infiltration. CONCLUSION: TLIP block improved analgesic efficacy in spine surgery compared with non-block care. Furthermore, current literature supported the TLIP block was superior to wound infiltration in terms of opioid consumption.

Lumbar medial branch cryoneurolysis under ultrasound guidance: initial report of five cases.

AIMS: To assess the feasibility and preliminary results of ultrasound guided medial branch cryoneurolysis in the management of facet joint syndrome. MATERIAL AND METHODS: Between March 2017 and August 2017, a total of 20 patients underwent medial branch blocks, 12 of which were positive. Five patients chose to participate in the study and 8 medial branch cryoneurolysis were performed. The primary endpoint of the study was the feasibility of the procedure. The secondary endpoint was the efficacy on pain assessed over the following year after the procedure. RESULTS: Technical feasibility of cryoneurolysis under ultrasound guidance was 100%. Accurate needle positioning at the accurate target in the angle between the posterior aspect of the transverse process and the lateral aspect of the facet joint was achieved in all cases. Needle progression could be depicted with US guidance in all cases. Mean pre-procedural Visual Analogue Scale and Oswestry disability Index scores were 6.8 (range 5-8) and 20.6 (range 12- 31), respectively. Follow up showed a decrease of Visual Analogue Scale score at one month (1.75, range 0-7), and at three months (1.75 range 0-3), Mean self-reported improvement at 6 months was 76% (60- 100%) and 77% at 12 months (50-100%). We report one case of failure at one month. No complications were noted during or after the procedure. CONCLUSION: Our findings suggest that ultrasound is a valid imaging modality to perform lumbar medial branch cryoneurolysis. Initial results show that cryoneurolysis under ultrasound guidance appears as a safe and effective procedure in patients suffering for facet joint pain.

Optical recording reveals topological distribution of functionally classified colorectal afferent neurons in intact lumbosacral DRG.

Neuromodulation as a non-drug alternative for managing visceral pain in irritable bowel syndrome (IBS) may target sensitized afferents of distal colon and rectum (colorectum), especially their somata in the dorsal root ganglion (DRG). Developing selective DRG stimulation to manage visceral pain requires knowledge of the topological distribution of colorectal afferent somata which are sparsely distributed in the DRG. Here, we implemented GCaMP6f to conduct high-throughput optical recordings of colorectal afferent activities in lumbosacral DRG, that is, optical electrophysiology. Using a mouse ex vivo preparation with distal colorectum and L5-S1 DRG in continuity, we recorded 791 colorectal afferents' responses to graded colorectal distension (15, 30, 40, and 60 mmHg) and/or luminal shear flow (20-30 mL/min), then functionally classified them into four mechanosensitive classes, and determined the topological distribution of their somata in the DRG. Of the 791 colorectal afferents, 90.8% were in the L6 DRG, 8.3% in the S1 DRG, and only 0.9% in the L5 DRG. L6 afferents had all four classes: 29% mucosal, 18.4% muscular-mucosal, 34% low-threshold (LT) muscular, and 18.2% high-threshold (HT) muscular afferents. S1 afferents only had three classes: 19.7% mucosal, 34.8% LT muscular, and 45.5% HT muscular afferents. All seven L5 afferents were HT muscular. In L6 DRG, somata of HT muscular afferents were clustered in the caudal region whereas somata of the other classes did not cluster in specific regions. Outcomes of this study can directly inform the design and improvement of next-generation neuromodulation devices that target the DRG to alleviate visceral pain in IBS patients.

Extradural Characteristics of the Origins of Lumbosacral Nerve Roots.

BACKGROUND AND STUDY AIMS: A great number of unsuccessful intervertebral herniated disk surgeries in the lumbosacral region have highlighted the importance of a comprehensive knowledge of the different types of nerve root anomalies. That knowledge gained by anatomical studies (and intraoperative findings) might contribute to better results. In our study we focused on intraspinal extradural lumbosacral nerve root anomalies and their possible role in radiculopathy. MATERIAL AND METHODS: The study was performed on 43 cadavers within 24 hours after death (32 men and 11 women). Bodies were dissected in the prone position, and a laminectomy exposed the entire spinal canal for the bilateral examination of each spinal nerve root from its origin to its exit through the intervertebral foramen or sacral hiatus. Uncommon extradural features in the lumbosacral region were pursued and documented. The spinal dural sac was also opened, aimed at recognizing the normotyped, prefixed, or postfixed type of plexus. RESULTS: A total of 20.93% of anomalies of extradural lumbosacral nerve root origins were observed, with the normotyped plexus prevailing. We observed atypical spacing of exits of lumbosacral roots (four cases), two roots leaving one intervertebral foramen (one case), extradural anastomoses (two cases), and missing extradural nerve root courses (two cases). The results were differentiated according to the normotyped, prefixed, or postfixed plexus type. CONCLUSION: Results of similar studies dealing with anomalies of lumbosacral nerve roots were aimed at improving the results of herniated disk surgeries because ∼ 10% of misdiagnoses are related to ignorance of anatomical variability. Our observations may help explain the differences between the clinical picture and generally accepted anatomical standards.

Quadratus lumborum block: are we aware of its side effects? A report of 2 cases / Bloqueio do quadrado lombar: estamos cientes de seus efeitos colaterais? Relato de dois casos

Abstract Background and objectives The quadratus lumborum block was initially described in 2007 and aims at blocking the same nerves as the ones involved on the Transverse Abdominis Plane block, while accomplishing some visceral enervation as well due to closer proximity with the neuroaxis and sympathetic trunk. Given its versatility, we have successfully used it in a wide range of procedures. We report two cases where we believe the dispersion of local anesthetic is likely to have led to a previously undescribed complication. Clinical reports We report two cases in which we performed a quadratus lumborum type II block and general anesthesia for total gastrectomy and right hemicolectomy. There were no noteworthy events while performing the block and inducing general anesthesia, but within 30-40 min serious hypotension and tachycardia were noted. As other motives for hypotension were ruled out, the event was interpreted as block-induced sympatholysis due to cephalad dispersion of the local anesthetic to the paravertebral and epidural space, and successfully managed with ephedrine and increase of the crystalloid infusion rate. Conclusions The quadratus Lumborum block is safe to execute and provides effective abdominal wall and visceral analgesia. However, the possibility of eliciting undesired episodes should prompt caution when performing this block and practitioners should thereafter remain vigilant. Questions regarding ideal dosing, volumes, timing of block and pertinence of catheters remain to be answered.

Resumo Justificativa e objetivos O bloqueio do quadrado lombar foi primeiramente descrito em 2007 e tem como objetivo o bloqueio dos mesmos nervos envolvidos no bloqueio do plano transverso abdominal, ao atingir algumas inervações viscerais, bem como devido à maior proximidade com o neuroeixo e cadeia simpática. Dada a sua versatilidade, temos usado esse bloqueio com sucesso em uma grande variedade de procedimentos. Relatamos dois casos nos quais acreditamos que a dispersão do anestésico local pode ter levado a uma complicação não descrita previamente. Relatos clínicos Relatamos dois casos nos quais realizamos o bloqueio do quadrado lombar tipo II e anestesia geral para gastrectomia total e hemicolectomia direita. Não houve eventos notáveis durante o bloqueio e a indução da anestesia geral, mas, dentro de 30 a 40 minutos, observamos grave hipotensão e taquicardia. Como outros motivos para a hipotensão foram descartados, o evento foi interpretado como simpatólise induzida pelo bloqueio devido à dispersão cefálica do anestésico local para os espaços paravertebral e epidural e tratado com sucesso com efedrina e aumento da taxa de infusão de cristaloides. Conclusões O bloqueio do quadrado lombar oferece segurança na execução e fornece analgesia eficaz à parede abdominal e vísceras. Porém, a possibilidade de provocar episódios indesejáveis requer cautela em sua execução e, por conseguinte, os médicos precisam estar atentos. As questões relacionadas à dosagem ideal, aos volumes, ao tempo de bloqueio e à pertinência dos cateteres permanecem indefinidas.

Morphologic Evaluation of Lumbosacral Nerve Roots in the Vertebral Foramen: Measurement of Local Pressure of the Intervertebral Foramen.

STUDY DESIGN: The prospective cohort study. OBJECTIVE OF THE STUDY: The objective was to evaluate the relationships between local pressure changes of the intervertebral foramen during lumbar spine extension and lumbar foraminal morphology. SUMMARY OF BACKGROUND DATA: The physiological states of lumbosacral nerve roots in the vertebral foramen remain controversial. METHODS: We evaluated 56 lumbosacral vertebral foramens in 21 patients with L4-degenerative spondylolisthesis. All patients underwent L4-5 posterolateral fusion (PLF). The local pressure of the intervertebral foramen was measured intraoperatively, and measurement was performed before and after L4-5 PLF. We defined the changes in the ratio of local pressure between lumbar flexion to extension as percent pressure. The sagittal angular motion, distance between the inferior cortex of the cranial pedicle and superior cortex of the caudal pedicle, posterosuperior margin of the superior vertebral body and superior articular facet, posteroinferior edge of the superior vertebral body and inferior articular facet, and the intervertebral disc height were measured using preoperative functional plain radiographs and CT images. RESULTS: The average local pressure of the intervertebral foramen significantly increased during lumbar extension. However, the L4-5 vertebral foraminal pressure after PLF were nearly identical. There was no significant correlation between percent pressure and lumbar range of motion. Furthermore, there were no significant correlations between percent pressure and each morphologic parameter of the lumbar foramen. CONCLUSIONS: There were no significant relationships between the lumbar foraminal morphology and intervertebral foraminal pressure changes during lumbar extension, and L4-5 vertebral foraminal pressure was not affected by the lumbar posture after L4-5 posterior fusion. On the basis of the results, the external dynamic stresses on the nerve roots in the vertebral foramen might be improved by lumbar posterior fusion using instrumentation without direct decompression of the vertebral foramen.

[The effects of sacral nerve root electrostimulation on the colon function and its mechanisms in a rat model of spinal cord injury].

OBJECTIVE: To study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI). METHODS: One hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8). RESULTS: In SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP.

Compression of Root Level in a Patient with Hereditary Neuropathy with Liability to Pressure Palsy Diagnosed by Magnetic Resonance Imaging.

Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by acute, painless, and recurrent mononeuropathies that are secondary to compression or minor trauma. This case is the first to report an intraspinal compression of the radicular nerve by schwannoma in a patient with HNPP. A 66-year-old woman developed left foot drop and paresthesia of the lateral aspects of left distal lower leg. An electromyography showed left L5 radiculopathy and severe peripheral polyneuropathy. A lumbosacral magnetic resonance imaging revealed a radicular nerve in the intradural and extramedullary space being compressed by schwannoma. She previously had symptoms of foot drop several years ago, and HNPP was confirmed by peripheral myelin protein 22 deletion. She was surgically treated for L5 radiculopathy, which might have been caused by a traction of the nerve root by schwannoma at the intradural and extramedullary space. After surgical treatment, her symptoms of foot drop had improved from zero grade to IV+ grade within 4 weeks. The occurrence of HNPP and schwannoma in the same patient may be coincidental, but it is tempting to speculate that they share a common genetic basis. Therefore, for patients with HNPP, it is important to consider not only an electrophysiologic study but also a magnetic resonance imaging to locate the exact pathologic site.

Effects of sacral nerve stimulation on postpartum urinary retention-related changes in rat bladder.

OBJECTIVE: To examine the effect of sacral nerve stimulation (SNS) on the urodynamic function and molecular structure of bladders in rats following acute urinary retention (AUR) after parturition. MATERIAL AND METHODS: Thirty primiparous rats were divided into three groups: postpartum, postpartum+AUR, and postpartum+AUR+SNS. AUR was achieved by clamping the distal urethra of a rat for 60 minutes. The postpartum+AUR+SNS group received electrical stimulation 60 minutes daily for 3 days after AUR. In addition to cystometric studies and external urethral sphincter electromyography, the expression of caveolins and nerve growth factor (NGF) and caveolae number in bladder muscle were analyzed. RESULTS: The postpartum+AUR group has significantly greater residual volume than the postpartum group, but the residual volume decreased significantly after SNS treatment. The postpartum+AUR group had significantly lower peak voiding pressure, a longer bursting period and lower amplitude of electromyograms of external urethral sphincter activity than the postpartum and postpartum+AUR+SNS groups. The postpartum+AUR rats had higher NGF expression, lower caveolin-1 expression, and fewer caveolae in bladder muscle compared with the postpartum rats. Conversely, the caveolin-1 expression and caveolae number increased, and the NGF expression decreased after SNS treatment. CONCLUSION: Bladder dysfunction after parturition in a rat model caused by AUR may be restored to the non-AUR structural and functional level after SNS treatment.

Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.

BACKGROUND: Symptom of herpes zoster is sometimes difficult to distinguish from sciatica induced by spinal diseases, including lumbar disc herniation and spinal canal stenosis. Here we report a case of sciatica mimicking lumbar canal stenosis. CASE PRESENTATION: A 74-year-old Chinese male patient visited our hospital for left-sided sciatic pain upon standing or walking for 5 min of approximately 1 month's duration. At the first visit to our hospital, there were no skin lesions. A magnetic resonance imaging showed spinal canal stenosis between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with sciatica induced by spinal canal stenosis. We considered decompression surgery for the stenosis of 4th and 5th lumbar spine because conservative therapy failed to relieve the patient's symptom. At that time, the patient complained of a skin rash involving his left foot for several days. A vesicular rash and erythema were observed on the dorsal and plantar surfaces of the great toe and lateral malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar spinal nerve area based on clinical findings, including the characteristics of the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti-inflammatory drugs. After 1 week of medication, the skin rash resolved and pain relief was obtained. CONCLUSION: In conclusion, spinal surgeons should keep in mind herpes zoster infection as one of the possible differential diagnoses of sciatica, even if there is no typical skin rash.

Comparison of radiation exposure during fluoroscopy-guided transforaminal epidural steroid injections at different vertebral levels.

OBJECTIVE: To estimate and compare radiation exposure during transforaminal fluoroscopy-guided epidural steroid injection (TFESI) at different vertebral levels. MATERIALS AND METHODS: Fluoroscopy-guided TFESI was performed in 181 patients. The patients were categorized into three groups according to the injected lumbosacral nerve level of L2-4, L5, or S1. Fluoroscopy time (FT) and dose area product (DAP) were recorded for all patients; correlations between FT and DAP were determined at each level, and both FT and DAP were compared between the different vertebral levels. RESULTS: The numbers of patients who received ESI at L2-4, L5, and S1 were 29, 123, and 29. Mean FT was 44 seconds at L2-4, 33.5 seconds at L5, and 37.7 seconds at S1. Mean DAP was 138.6 µGy·m(2) at L2-4, 100.6 µGy·m(2) at L5, and 72.1 µGy·m(2) at S1. FT and DAP were positively correlated in each group (p values < 0.001). FT was significantly shorter at L5 than that at L2-4 (p = 0.004) but was not significantly different between S1 and L2-4 or L5 (p values = 0.286 and 0.532, respectively). DAP was significantly smaller at L5 and S1 than that at L2-4, but L5 and S1 were not significantly different. After correcting for FT, DAP was significantly smaller at S1 than that at either L2-4 or L5 (p values = 0.001 and 0.010). CONCLUSION: The radiation dose was small during a single procedure of ESI and showed differences between different lumbosacral spine levels.

Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen.

Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR in ovariectomized rats, but its effects were normalized with 4 days of oestrogen treatment. Bilateral nanoinjection of SHU9119 into the paraventricular nucleus of the hypothalamus (PVN), to block α-melanocyte-stimulating hormone (α-MSH) type 3 and 4 receptors, decreased LSNA in leptin-treated pro-oestrus but not dioestrus rats. Unlike leptin, i.c.v. insulin infusion increased basal and baroreflex control of LSNA and HR similarly in pro-oestrus and dioestrus rats; these responses did not differ from those in male rats. We conclude that, in female rats, leptin's stimulatory effects on SNA are differentially enhanced by oestrogen, at least in part via an increase in α-MSH activity in the PVN. These data further suggest that the actions of leptin and insulin to increase the activity of various sympathetic nerves occur via different neuronal pathways or cellular mechanisms. These results may explain the poor correlation in females of SNA with adiposity, or of MAP with leptin.

Survival of neural stem cell grafts in the lesioned spinal cord is enhanced by a combination of treadmill locomotor training via insulin-like growth factor-1 signaling.

Combining cell transplantation with activity-based rehabilitation is a promising therapeutic approach for spinal cord repair. The present study was designed to investigate potential interactions between the transplantation (TP) of neural stem cells (NSCs) obtained at embryonic day 14 and treadmill training (TMT) in promoting locomotor recovery and structural repair in rat contusive injury model. Combination of TMT with NSC TP at 1 week after injury synergistically improved locomotor function. We report here that combining TMT increased the survival of grafted NSCs by >3-fold and >5-fold at 3 and 9 weeks after injury, respectively. The number of surviving NSCs was significantly correlated with the extent of locomotor recovery. NSCs grafted into the injured spinal cord were under cellular stresses induced by reactive nitrogen or oxygen species, which were markedly attenuated by TMT. TMT increased the concentration of insulin-like growth factor-1 (IGF-1) in the CSF. Intrathecal infusion of neutralizing IGF-1 antibodies, but not antibodies against either BDNF or Neurotrophin-3 (NT-3), abolished the enhanced survival of NSC grafts by TMT. The combination of TP and TMT also resulted in tissue sparing, increased myelination, and restoration of serotonergic fiber innervation to the lumbar spinal cord to a larger extent than that induced by either TP or TMT alone. Therefore, we have discovered unanticipated beneficial effects of TMT in modulating the survival of grafted NSCs via IGF-1. Our study identifies a novel neurobiological basis for complementing NSC-based spinal cord repair with activity-based neurorehabilitative approaches.

Photoplethysmographic signals to predict the success of lumbar sympathetic blockade for lower extremity pain.

OBJECTIVE: A prospective, observational study to investigate how photoplethysmography (PPG) signals change during lumbar sympathetic blockade (LSB), and whether these changes can predict sympathetically mediated pain (SMP). METHODS: Patients with unilateral lower extremity pain and self-reported cold hyperalgesia underwent LSB. Bilateral temperature and PPG signals (AC and DC) were recorded. Power spectrum analysis (PSA) was performed. RESULTS: Of the total patient cohort (n = 38), eight patients (22.1%) had excellent pain-relief after LSB and were determined to have SMP. In all patients, the PPG AC signal changed immediately after drug administration, before any temperature change. DC signals decreased slowly in a linear fashion. PSA of DC signals showed significantly lower low-frequency/high-frequency (LF/HF) ratios in the SMP group than the sympathetically independent pain group, both before and after LSB. A cut-off value of 2.92 for LF/HF resulted in sensitivity, specificity and positive predictive values for SMP of 75.0%, 76.7% and 3.21 [1.5, 6.9], respectively. CONCLUSIONS: PPG may be used as an early indicator of a successful LSB and could also be helpful in diagnosing SMP.

Nerve injury and recovery after lateral lumbar interbody fusion with and without bone morphogenetic protein-2 augmentation: a cohort-controlled study.

BACKGROUND CONTEXT: Despite common use of intraoperative electrophysiologic neuromonitoring, injuries to the lumbar plexus during lateral lumbar interbody fusion (LLIF) have been reported. Emerging data suggest that recombinant human bone morphogenetic protein-2 (rhBMP-2) use during an anterior or transforaminal lumbar interbody fusion may be associated with an increased risk of neurological deficit. Clinical data on the sequelae of rhBMP-2 implantation in close proximity to the lumbosacral plexus during LLIF remains to be understood. PURPOSE: The purpose of this study was to compare the incidence of neurologic deficits and pain in patients undergoing LLIF with and without rhBMP-2. STUDY DESIGN/SETTING: Retrospective outcome analysis in controlled cohorts undergoing the lateral exposure technique for LLIF with and without rhBMP-2. METHODS: The electronic medical records of patients undergoing LLIF with and without supplemental posterior fusion for degenerative spinal conditions were retrospectively reviewed over a 6-year period. Patients with previous lumbar spine surgery or follow-up of less than 6 months were excluded. Patients were divided into 2 groups, Group 1 (rhBMP-2 use; n=72) and Group 2 (autograft/allograft use; n=72), and were matched according to the age at the time of surgery, gender, weight, body mass index, side of approach, total number of treated spinal segments, use of supplemental posterior fusion, and length of follow-up. RESULTS: Immediately after surgery, a sensory deficit was recorded in 33 patients in Group 1 and 35 patients in Group 2 (odds ratio [OR] 0.895; 90% confidence interval [CI] 0.516-1.550; p=.739). At last follow-up, a persistent sensory deficit was identified in 29 patients whose LLIF procedure was supplemented by rhBMP-2 and 20 patients in whom autograft/allograft was used (OR 1.754; 90% CI 0.976-3.151; p=.115). A motor deficit was recorded in 37 patients immediately after the rhBMP-2 procedure and 28 patients treated with autograft/allograft (OR 1.661; 90% CI 0.953-2.895; p=.133). A persistent motor deficit was recorded in 35 and 17 patients in Groups 1 and 2, respectively, at last follow-up (OR 3.060; 90% CI 1.681-5.571; p=.002). During the first postoperative examination, 37 patients in Group 1 and 25 patients in Group 2 complained of anterior thigh or groin pain (OR 1.987; 90% CI 1.133-3.488; p=.045). At last follow-up, there was a significantly higher number of patients in Group 1 who complained of persistent anterior thigh or groin pain than Group 2 (8 vs. 0 patients) (OR 16.470; 90% CI 1.477-183.700; p=.006). CONCLUSIONS: Our results provide evidence of an increased rate of postoperative neurologic deficit and anterior thigh/groin pain after LLIF using rhBMP-2, when compared with matched controls without rhBMP-2 exposure. This study suggests a potential direct deleterious effect of rhBMP-2 on the lumbosacral plexus.

Recovery of sensory and supraspinal control of leg movement in people with chronic paraplegia: a case series.

OBJECTIVE: To report on unexpected findings in 4 patients with chronic paraplegia who underwent the laparoscopic implantation of neuroprosthesis procedure in the pelvic lumbosacral nerves. DESIGN: Observational case series. SETTING: Tertiary referral unit specialized in advanced gynecological surgery and neuropelveology. PARTICIPANTS: Three patients with incomplete American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade B (n=2) and AIS grade C (n=1) spinal cord injury (SCI) and 1 patient with flaccid complete chronic SCI (AIS grade A) (n=1). INTERVENTION: Functional electrical stimulation (FES)-assisted locomotor training and continuous low-frequency pelvic-lumbosacral neuromodulation. MAIN OUTCOME MEASURES: Change in ASIA Lower Extremity Motor Scores, ASIA sensory scores for light touch and pinprick sensation, and Walking Index for Spinal Cord Injury scores. RESULTS: All 4 patients developed progressive recovery of some sensory and voluntary motor functions below the lesions. Three are currently capable of voluntary weight-bearing standing and walking a few meters with a walker without FES. The first patient with the longest follow-up is even capable of electrically assisted standing/walking with 2 crutches without braces or assistance for a distance of about 900 meters, and of weight-bearing standing and walking for 30 meters with a walker without stimulation. CONCLUSIONS: We report unexpected sensory and locomotor recovery in 4 people with paraplegia with SCI. Our findings suggest that FES-assisted locomotor training with continuous low-frequency pelvic nerve stimulation in patients with SCI may induce changes that affect the central pattern generator and allow supra- and infraspinal inputs to engage residual spinal pathways.

Nucleus tractus solitarii A(2a) adenosine receptors inhibit cardiopulmonary chemoreflex control of sympathetic outputs.

Previously we have shown that stimulation of inhibitory A1 adenosine receptors located in the nucleus tractus solitarii (NTS) attenuates cardiopulmonary chemoreflex (CCR) evoked inhibition of renal, adrenal and lumbar sympathetic nerve activity and reflex decreases in arterial pressure and heart rate. Activation of facilitatory A2a adenosine receptors, which dominate over A1 receptors in the NTS, contrastingly alters baseline activity of regional sympathetic outputs: it decreases renal, increases adrenal and does not change lumbar nerve activity. Considering that NTS A2a receptors may facilitate release of inhibitory transmitters we hypothesized that A2a receptors will act in concert with A1 receptors differentially inhibiting regional sympathetic CCR responses (adrenal>lumbar>renal). In urethane/chloralose anesthetized rats (n=38) we compared regional sympathetic responses evoked by stimulation of the CCR with right atrial injections of serotonin 5HT3 receptor agonist, phenylbiguanide, (1-8µg/kg) before and after selective stimulation, blockade or combined blockade and stimulation of NTS A2a adenosine receptors (microinjections into the NTS of CGS-21680 0.2-20pmol/50nl, ZM-241385 40pmol/100nl or ZM-241385+CGS-21680, respectively). We found that stimulation of A2a adenosine receptors uniformly inhibited the regional sympathetic and hemodynamic reflex responses and this effect was abolished by the selective blockade of NTS A2a receptors. This indicates that A2a receptor triggered inhibition of CCR responses and the contrasting shifts in baseline sympathetic activity are mediated via different mechanisms. These data implicate that stimulation of NTS A2a receptors triggers unknown inhibitory mechanism(s) which in turn inhibit transmission in the CCR pathway when adenosine is released into the NTS during severe hypotension.

Multifidus innervation and muscle assessment post-spinal surgery.

PURPOSE: Assessment of the integrity of the multifidus muscles and corresponding nerve roots, post-open (OSS) versus minimally invasive spinal surgery (MISS) for lumbar spine fractures. METHODS: We investigated the first six patients undergoing MISS in our institution and age- and sex-matched them with 6 random patients who previously had OSS. All had a similar lumbar fracture configuration without evidence of spinal cord injury. All were assessed using ultrasound muscle quantification and electromyographic studies at a minimum of 6 months post-operatively. Mean cross-sectional area (CSA) was measured at sequential levels within and adjacent to the operative field. Concentric needle electromyography was performed at instrumented and adjacent non-instrumented levels in each patient. RESULTS: Mean CSA across all lumbar multifidus muscles was 4.29 cm(2) in the MISS group, 2.26 cm(2) for OSS (p = 0.08). At the instrumented levels, mean CSA was 4.21 cm(2) for MISS and 2.03 cm(2) for OSS (p = 0.12). At non-instrumented adjacent levels, mean CSA was 4.46 cm(2) in the MISS group, 2.87 cm(2) for OSS (p = 0.05). Electromyography at non-instrumented adjacent levels demonstrated nerve function within normal limits in 5/6 levels in the MISS group compared to 1/6 levels in the OSS (p = 0.03). Instrumented levels demonstrated nerve function within normal limits in 5/12 levels in the MISS group compared with 4/12 in the OSS group, including moderate-severe denervation at 5 levels in the OSS group (p = 0.15). CONCLUSIONS: Posterior instrumented MISS demonstrates a significantly superior preservation of the medial branch of the posterior ramus of the spinal nerve and less muscle atrophy, particularly at adjacent levels when compared to OSS.