Spinal Nerve Research Articles

Combined antiallodynic effects of Neurotropin®–tramadol and Neurotropin®–mirogabalin in rats with L5-spinal nerve ligation

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50–200 NU/kg, p.o.), tramadol (7.5–60 mg/kg, p.o.), and mirogabalin (3–30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100–400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30–100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100–400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10–100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin–tramadol or Neurotropin–mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

Harmonization of Longitudinal Diffusion Tensor Imaging Data of the Pediatric Cervical and Thoracic Spinal Cord at 3T Using Longitudinal ComBat.

Diffusion tensor imaging (DTI) of the spinal cord has been extensively used to identify biomarkers for spinal cord pathology. Previously, the longitudinal ComBat (longComBat) technique was examined to reduce scanner effects in multi-site, multi-scanner spinal cord DTI data. This study aimed to assess its effectiveness on longitudinal scans using a single-scanner pediatric dataset, including healthy and spinal cord injury (SCI) subjects. Two identical datasets were collected from 42 healthy and 27 SCI subjects with a 2-hour interval between scans on a 3T Siemens MRI scanner. Axial DTI images of the entire cervical and thoracic spinal cord were obtained, and various average diffusion tensor metrics (FA, MD, RD, & AD) were measured at each vertebral level. Pearson correlation and intraclass correlation coefficients were used to evaluate inter- and intra-subject agreement pre- and post-harmonization. Minimal improvement in agreement was observed with the mean square residual (MSR) model, while the restricted maximum likelihood estimator (REML) model showed reduced intra-subject agreement in all the tensor metrics. The significant variability between longitudinal DTI scans within a single scanner was likely due to physiological motion rather than scanner effects. Post-harmonization using the longComBat MSR model showed limited improvement in agreement.

Rat Model of Neuropathic Pain Induced by Spinal Nerve Ligation: A New Approach via an Oblique Lateral Incision.

The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach. 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1β in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation. Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1β were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups. This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma.

Erector spinae plane infiltration and anterior rami of spinal nerve: a cadaveric study

BackgroundThe erector spinae plane block (ESP block) is frequently employed for thoracic, abdominal, and spinal surgeries, yet its precise mechanism of action remains a subject of debate. While initially postulated...

The Outcome of Spinal Accessory Nerve Transfer to the Musculocutaneous Nerve in Birth Brachial Plexus Palsy

Patients with brachial plexus birth injury with limited intraplexal donors require the use of extraplexal donors. Concern regarding the potential for respiratory problems resulting from the harvest of intercostal nerves or the phrenic nerve suggests the need for other options. Transfer of the spinal accessory nerve (SAN) is one option for restoring elbow flexion in adult patients; however, there are few reports of the results of this transfer in brachial plexus birth injury. This study aimed to report the result of SAN transfer to the musculocutaneous nerve (MCN) in brachial plexus birth injury. Patients who had undergone SAN to MCN nerve transfer were included in thisstudy. Patients were classified according to Narakas classification. The chart was reviewed for the time for recovery of elbow flexion according to the Active Movement Scale(AMS). Eleven patients underwent SAN to MCN transfers with interpositional sural nerve grafts. Mean birthweight was 4,070 grams (range: 3,300-4,670). Mean time to operation was 6.5 months (range: 4-10). Of the 11 patients, two were of Narakas type 3, whereas the others were of type 4. One patient did not recover elbow flexion and underwent later tendon transfer, whereas the other 10 patients reached AMS grade M6 recovery. The median time for AMS grade M1 elbow flexion recovery was eight months (interquartile range: 6.2-8.8) and for AMS grade M5 was 26 months (interquartile range: 14.2-36.5). Spinal accessory nerve to MCN transfer with an interposition nerve graft is a viable option for restoring elbow flexion. However, long-term outcomes of this procedure have yet to be fully demonstrated. Case series IV.

Anti-sulfatide antibody associated GBS with headache and abdominal pain: a case report

BackgroundGuillain‒Barre syndrome (GBS) is an acute inflammatory peripheral neuropathy caused by autoimmunity. Gangliosides and sulfatides are important components of peripheral nerves. Anti-sulfatide antibody-mediated complement is associated with acute sensorimotor peripheral neuropathy in GBS, which is characterized by pain and paresthesias.Case presentationThe child was a 7-year-old girl with headache and abdominal pain, followed by limb numbness and pain. Cranial imaging showed ventricular dilatation, peripheral nerve function conduction examination showed polyradiculopathy, and cerebrospinal fluid tests showed normal cell counts but elevated protein levels, all of which led to the diagnosis of GBS. After treatment with intravenous immunoglobulin (400 mg/kg × 5 days), the symptoms did not improve, and muscle strength progressively worsened, accompanied by paroxysmal complexion flushing, heart rate fluctuation, hyperhidrosis, and a progressive increase in cerebrospinal fluid protein (up to 3780.1 mg/L). On the basis of these findings combined with serum anti-sulfatide IgM positivity, anti-sulfatide antibody-related GBS was considered, and treatment with low-dose prednisolone (1 mg/kg/d) led to symptom improvement.ConclusionsAnti-sulfatide antibody-associated GBS is associated with small fiber peripheral neuropathy. The main manifestations are pain, paresthesias and autonomic dysfunction. In addition to the dysfunction of spinal nerve root absorption caused by increased cerebrospinal fluid protein, autonomic dysfunction may be involved in pain. When the therapeutic effect of immunoglobulin is not satisfactory, a low dose and short course of corticosteroids can be considered, and the prognosis is good.

CTSD upregulation as a key driver of spinal ligament abnormalities in spinal stenosis

Spinal stenosis (SS) is frequently caused by spinal ligament abnormalities, such as ossification and hypertrophy, which narrow the spinal canal and compress the spinal cord or nerve roots, leading to myelopathy or sciatic symptoms; however, the underlying pathological mechanism is poorly understood, hampering the development of effective nonsurgical treatments. Our study aims to investigate the role of co-expression hub genes in patients with spinal ligament ossification and hypertrophy. To achieve this, we conducted an integrated analysis by combining RNA-seq data of ossification of the posterior longitudinal ligament (OPLL) and microarray profiles of hypertrophy of the ligamentum flavum (HLF), consistently pinpointing CTSD as an upregulated hub gene in both OPLL and HLF. Subsequent RT-qPCR and IHC assessments confirmed the heightened expression of CTSD in human OPLL, ossification of the ligamentum flavum (OLF), and HLF samples. We observed an increase in CTSD expression in human PLL and LF primary cells during osteogenic differentiation, as indicated by western blotting (WB). To assess CTSD's impact on osteogenic differentiation, we manipulated its expression levels in human PLL and LF primary cells using siRNAs and lentivirus, as demonstrated by WB, ALP staining, and ARS. Our findings showed that suppressing CTSD hindered the osteogenic differentiation potential of PLL and LF cells, while overexpressing CTSD activated osteogenic differentiation. These findings identify CTSD as a potential therapeutic target for treating spinal stenosis associated with spinal ligament abnormalities.

Upper cervical spine syndrome: A new perspective

Headaches are widespread in Western Society; they affect approximately 50% of the adult population in the United States. Headaches can present with a variety of clinical and regional symptoms. Although a headache disorder classification system exists, clinical experience has identified various overlapping causes for headaches. It remains clinically challenging to identify the exact etiology causing headaches. For example, the underlying mechanism of cervicogenic headaches remains elusive, but the upper cervical spine plays a key role. Abnormal upper cervical movement patterns, in combination with muscular dysfunctions, are a possible contributing factor to headaches. The upper vertebral spinal nerves C0-C3 have been correlated with cervicogenic headaches. It has been established that biomechanical dysfunction of the upper cervical spine can contribute to neck pain. The atlas plays a key role in the biomechanical dysfunction in the upper cervical spine. Previously, it has been identified that the relative position of the atlas to the axis correlates with headaches. Additionally, it has been demonstrated that an extended contraction of the homolateral obliquus capitis inferior muscles can result in positional default rotation of the atlas. As managing headaches remains multimodal and challenging, there is enough evidence to support the inclusion of the upper cervical spine to normalize joint position, joint mobility, muscle tonicity, and upright positioning. When recognizing the “upper cervical syndrome” and addressing the functioning of the atlas, clinical outcomes will improve for those treating patients with headaches.

Analgesic Effect of SKI306X on Chronic Postischemic Pain and Spinal Nerve Ligation-Induced Neuropathic Pain in Mice.

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

Spinal Accessory Nerve to Suprascapular Nerve Transfer by Dorsal Approach for Shoulder Reanimation in Cases of Brachial Plexus Injuries: Surgical Technique

Spinal Accessory Nerve to Suprascapular Nerve Transfer by Dorsal Approach for Shoulder Reanimation in Cases of Brachial Plexus Injuries: Surgical Technique

The Efficacy of a Multidisciplinary Approach and Diagnostic-Therapeutic Algorithm for Vertebral Metastases with Spinal Cord Compression.

Background and Objectives: Metastatic spinal cord compression represents a substantial risk to patients, given its potential for spinal cord and/or nerve root compression, which can result in severe morbidity. This study aims to evaluate the effectiveness of a diagnostic-therapeutic algorithm developed at our hospital to mitigate the devastating consequences of spinal cord compression in patients with vertebral metastases. Materials and Methods: The algorithm, implemented in our practice in January 2022, is based on collective clinical experience and involves collaboration between emergency room physicians, oncologists, spine surgeons, neuroradiologists, radiation oncologists, and oncologists. To minimize potential confounding effects from the COVID-19 pandemic, data from the years 2019 and 2021 (pre-protocol) were collected and compared with data from the years 2022 and 2023 (post-protocol), excluding the year 2020. Results: From January 2022 to December 2023, 488 oncological patients were assessed, with 45 presenting with urgency due to suspected spinal cord compression. Out of these, 44 patients underwent surgical procedures, with 25 performed in emergency settings and 19 cases in elective settings. Comparatively, in 2019 and 2021, 419 oncological patients were evaluated, with 28 presenting with urgency for suspected spinal cord compression. Of these, 17 underwent surgical procedures, with 10 performed in emergency scenarios and 7 in elective scenarios. Comparing the pre-protocol period (years 2019 and 2021) to the post-protocol period (years 2022 and 2023), intrahospital consultations (commonly patients neurologically compromised) for spine metastasis decreased (105 vs. 82), while outpatient consultations increased remarkably (59 vs. 124). Discussion: Accurate interpretation of symptoms within the context of metastatic involvement is crucial for patients with a history of malignancy, whether presenting in the emergency room or oncology department. Even in the absence of a cancer history, careful interpretation of pain characteristics and clinical signs is crucial for diagnosing vertebral metastasis with incipient or current spinal cord compression. Early surgical or radiation intervention is emphasized as it provides the best chance to prevent deficits or improve neurological status. Preliminary findings suggest a notable increase in both the number of patients diagnosed with suspected spinal cord compression and the proportion undergoing surgical intervention following the implementation of the multidisciplinary protocol. The reduced number of intrahospital consultations (commonly patients neurologically compromised) and the increased number of visits of outpatients with vertebral metastases indicate a heightened awareness of the issue, leading to earlier identification and intervention before neurological worsening necessitating hospitalization. Conclusions: A comprehensive treatment planning approach is essential, and our multidisciplinary algorithm is a valuable tool for optimizing patient outcomes. The protocol shows potential in improving timely management of spinal cord compression in oncological patients. Further analysis of the factors driving these changes is warranted. Limitations: This study has limitations, including potential biases from the retrospective nature of data collection and the exclusion of 2020 data due to COVID-19 impact. To enhance the robustness of our results, long-term studies are required. Moreover, the single-center study design may limit the validity of the findings. Further multicenter studies would be beneficial for validating our results and exploring underlying factors in detail.

(082) DELAYED ORGASM CAN RESULT FROM LUMBOSACRAL DISC DISEASE DISRUPTING GENITAL SENSORY TRANSMISSION IN THE CAUDA EQUINA: A REVIEW

Abstract Introduction Delayed orgasm may be considered an unwanted, atypically long latency during most genital/sexual activity despite sexual stimulation, causing significant distress to the individual and/or partner, persisting for at least 6 months. Delayed orgasm is reported to affect 6.9% of women. It is associated with negative effects on sexual function, sexual satisfaction, and relationship satisfaction. Pharmacologic, endocrinologic, and neurobiological pathophysiological factors have been identified as possible etiologies of delayed orgasm, but an under-researched etiology is lumbosacral disc disease, specifically lumbosacral annular tear-induced sacral radiculopathy. The pelvic, pudendal, and sciatic nerves all merge at the S2-4 foramina where they coalesce to form the S2-4 nerve roots. These sacral spinal nerve roots (S2-4) ascend to the first synapse in the conus medullaris. During their ascent, they can be irritated mechanically by impingement/compression or chemically by exposure to the extruded nucleus pulposus from lumbosacral annular tears, and thereby disrupt genital sensory transmission with resultant delayed orgasm. The new evidence that delayed orgasm can be successfully treated by endoscopic spine surgery supports the association of delayed orgasm with sacral radiculopathy. There is still a paucity of research regarding delayed orgasm from lumbosacral disc disease. Objective To review the existing literature concerning the contribution of lumbosacral disc disease to delayed orgasm. Methods A literature search on delayed orgasm, its impacts and possible etiologies was performed. The following keywords were searched on Pubmed individually and in combination, related to the association between delayed orgasm and lumbosacral disc disease: delayed orgasm, delayed ejaculation, sexual dysfunction, anorgasmia, and persistent genital arousal disorder. Current definitions were compiled, and overall epidemiology, anatomy, and biopsychosocial factors of delayed orgasm were explored. Results There are a number of publications (n = 19) demonstrating the development of sexual dysfunction after damage to the sacral spinal nerve roots. Furthermore, several studies (n = 4) and case reports (n = 1) have demonstrated that treating lumbosacral disc disease reduces sexual dysfunction including improvement in delayed or reduced ejaculation. While delayed ejaculation encompasses the experience of delayed orgasm for some individuals, the literature fails to address delayed orgasm comprehensively in relation to lumbosacral disc disease, and thus fails to address treatment of lumbosacral disc disease and subsequent resolution of delayed orgasm. People with vulvas are particularly underrepresented in the literature studying the connection between lumbosacral disc disease and delayed orgasm. Conclusions While lumbosacral disc disease has many side effects that may impede daily function, sexual side effects can further detract from one’s personal life and relationship satisfaction. Thus, improving clinician awareness of sexual side effects, particularly delayed orgasm, can help improve treatment for individuals especially as they age. Further research is needed to strengthen the understanding of the effect of sacral radiculopathy on delayed orgasm as well as other sexual dysfunctions. Disclosure No.

The effect of preemptive retrolaminar block on lumbar spinal decompression surgery.

Spinal decompression surgery causes severe pain. Retrolaminar block (RLB) is block, which is done by infiltration of local anesthetic to block spinal nerves between the lamina and superior costotransversospinalis muscle. The primary aim of this study is to evaluate the effectiveness of RLB on postoperative analgesia in patients undergoing spinal surgery. Secondary aims are effects on additional anesthetic and analgesic consumption. The sixty (60) patients who underwent lumbar spinal surgery between May 2020 and May 2021 under general anesthesia with or without applied preemptive RLB for postoperative analgesia were included in this prospective observational study. Group I received ultrasound-guided preemptive RLB. In Group II, no intervention was performed. Postoperative VAS scores were compared in groups as primary outcome, perioperative additional anesthetic and analgesic needs were compared as secondary outcome. There was a significant difference between the groups in favor of the RLB group in terms of postoperative VAS scores at rest [1.33 (0.33-3.509)] and movement [2.40 (1.20-4.00)] (p < 0.001). Perioperative sevoflurane consumption was significantly low in block group (p < 0.001). Postoperative tramadol consumption was lower in Group I compared with Group II [Group 1: 200 (100-300); Group 2: 37.5 (0-200); p < 0.001]. Preemptive RLB may be used to reduce patients' pain in lumbar decompression surgery as well as to be part of a multimodal analgesia and anesthesia regimen to reduce anesthetic and analgesic drug consumption. Trial registration numberClinicalTrials.gov (No. NCT04209907).

Strategies and safety simulations for ultrasonic cervical spinal cord neuromodulation

Objective. Focused ultrasound spinal cord neuromodulation has been demonstrated in small animals. However, most of the tested neuromodulatory exposures are similar in intensity and exposure duration to the reported small animal threshold for possible spinal cord damage. All efforts must be made to minimize the risk and assure the safety of potential human studies, while maximizing potential treatment efficacy. This requires an understanding of ultrasound propagation and heat deposition within the human spine. Approach. Combined acoustic and thermal modelling was used to assess the pressure and heat distributions produced by a 500 kHz source focused to the C5/C6 level via two approaches (a) the posterior acoustic window between vertebral posterior arches, and (b) the lateral intervertebral foramen from which the C6 spinal nerve exits. Pulse trains of fifty 0.1 s pulses (pulse repetition frequency: 0.33 Hz, free-field spatial peak pulse-averaged intensity: 10 W cm−2) were simulated for four subjects and for ±10 mm translational and ±10∘ rotational source positioning errors. Main results. Target pressures ranged between 20%–70% of free-field spatial peak pressures with the posterior approach, and 20%–100% with the lateral approach. When the posterior source was optimally positioned, peak spine heating values were below 1 ∘C, but source mispositioning resulted in bone heating up to 4 ∘C. Heating with the lateral approach did not exceed 2 ∘C within the mispositioning range. There were substantial inter-subject differences in target pressures and peak heating values. Target pressure varied three to four-fold between subjects, depending on approach, while peak heating varied approximately two-fold between subjects. This results in a nearly ten-fold range between subjects in the target pressure achieved per degree of maximum heating. Significance. This study highlights the utility of trans-spine ultrasound simulation software and need for precise source-anatomy positioning to assure the subject-specific safety and efficacy of focused ultrasound spinal cord therapies.

Description and Evaluation of Dye and Contrast Media Distribution of Ultrasound-Guided Rectus Sheath Block in Cat Cadavers.

The rectus sheath block is an ultrasound-guided anaesthetic technique which aims to provide analgesia to the abdominal midline. This study aimed to assess the distribution of 0.4 mL kg-1 of a mixture of methylene blue and iopromide injected into each hemiabdomen in the internal rectus sheath in cat cadavers. We hypothesise that this technique would be feasible and would cover the rami ventrales of the last thoracic and the first lumbar spinal nerves. The study was divided into two phases. Phase 1 aimed to study the anatomical structures of the ventral abdominal wall (four cats were dissected). Phase 2 (ten cadavers) consisted of an ultrasound-guided injection of the mixture mentioned above and the assessment of its distribution by computed tomography and anatomical dissection. The results showed the staining of the cranioventral abdominal wall with a craniocaudal spread of four (three to eight) vertebral bodies. Methylene blue stained three (one to four) rami ventrales, affecting T10 (60%), T11 (100%), T12 (90%), T13 (50%) and L1 (5%). Based on these results, it could be stated that this technique could supply anaesthesia to the midline of the abdominal midline cranial to the umbilicus in clinical patients, but it may not be able to provide anaesthesia to the middle and caudal midline abdominal region.

Intraoperative Spinal Accessory Nerve Monitoring During Neck Dissection Surgery as a Predictor for Shoulder Dysfunction

Intraoperative Spinal Accessory Nerve Monitoring During Neck Dissection Surgery as a Predictor for Shoulder Dysfunction

ScnML models single-cell transcriptome to predict spinal cord neuronal cell status.

Injuries to the spinal cord nervous system often result in permanent loss of sensory, motor, and autonomic functions. Accurately identifying the cellular state of spinal cord nerves is extremely important and could facilitate the development of new therapeutic and rehabilitative strategies. Existing experimental techniques for identifying the development of spinal cord nerves are both labor-intensive and costly. In this study, we developed a machine learning predictor, ScnML, for predicting subpopulations of spinal cord nerve cells as well as identifying marker genes. The prediction performance of ScnML was evaluated on the training dataset with an accuracy of 94.33%. Based on XGBoost, ScnML on the test dataset achieved 94.08% 94.24%, 94.26%, and 94.24% accuracies with precision, recall, and F1-measure scores, respectively. Importantly, ScnML identified new significant genes through model interpretation and biological landscape analysis. ScnML can be a powerful tool for predicting the status of spinal cord neuronal cells, revealing potential specific biomarkers quickly and efficiently, and providing crucial insights for precision medicine and rehabilitation recovery.

Modelling of impulse activity of afferent fibers of antagonist muscles during transcutaneous electrical stimulation of the spinal cord during walking

The article describes the results of studies on the impulse activity of various groups of afferent fibers and EMG patterns of lower leg antagonist muscles when walking without, during and after transcutaneous electrical stimulation of the dorsal roots of the lower thoracic spinal cord of a person. Using a mathematical model based on the prediction of the triggering of muscle spindles, variability in the manifestation of impulse activity of various afferents tibialis anterior muscle (TA) and gastrocnemius medialis muscle (GM) when walking under different experimental conditions is shown. It was found that walking on a movable treadmill tape in the absence of spinal cord stimulation was accompanied by strong impulse activity of afferents I (Ia and Ib) and II groups GM, increased excitability of its motorneuron pool and weakening of afferent activity and excitability of TA. On the contrary, electrical stimulation of the spinal cord during walking caused strong impulsive activity of group II TA afferents and moderate — GM, while the activity of Ia fibers TA and GM decreased to moderate impulsivity, Ib afferents of the same muscles had the weakest activity, and the excitability of the GM motorneuron pool was greater than TA. During the postactivation period, walking was accompanied by increased impulses of afferent fibers of group Ib and II GM, weakening of afferent flows of Ib TA and Ia afferents GM, but along with this, afferent signals of group Ia and II to the motorneuron nucleus TA decreased to moderate impulses, and excitability of the motorneuron pool GM was higher than TA. The supposed reflex mechanisms of locomotion regulation are discussed on the basis of well-known phenomena associated with the interaction of various afferent inputs to the spinal cord neuronal apparatus in the system of lower leg antagonist muscles.

Intrathecal gastrodin alleviates allodynia in a rat spinal nerve ligation model through NLRP3 inflammasome inhibition

BackgroundGastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer’s disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats.MethodsIntrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.ResultsThe expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.ConclusionsExpression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.

Primary phenotypic features associated with caudal neck pathology in warmblood horses.

Detailed descriptions of clinical signs associated with radiological findings of the caudal cervical vertebral column are not available. Describe the clinical features associated with neck pain or stiffness, neck-related thoracic limb lameness, proprioceptive ataxia consistent with a cervicothoracic spinal cord or nerve lesion, and their frequency of occurrence compared with control horses. A total of 223 Warmblood horses. Case-control study. Controls and cases were recruited prospectively. All horses underwent predetermined lameness and neurologic examinations. The frequency of occurrence of each clinical feature was compared between cases and controls and relative risk (RR) were calculated. Ninety-six cases and 127 controls were included. Forty-seven (49%) of the cases were classified as neurologic, 31 (32.3%) had thoracic limb lameness, and 18 (18.7%) had neck stiffness or pain or both. Focal caudal cervical muscle atrophy (46, 47.9%), hypoesthesia (38, 39.6%), patchy sweating (16, 16.7%), hyperesthesia (11, 11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (58, 60.4%) were only observed in cases (P < .001). Sideways flexion of the neck was restricted in a higher proportion of cases (47/96, 49%) compared with controls (40/127, 31.8%; P = .009, RR 1.5). Hopping-type thoracic limb lameness was only observed in cases, (30, 31.6%). Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (41.9%) cases. Systematic clinical evaluation using the methods described should enable clinical differentiation between horses with caudal cervical lesions and horses with other causes of gait abnormalities.