Cord Substance Research Articles

Correlation between Duration of Preoperative Motor Deficit and Early Postoperative Motor Functional Recovery in Patients with Intradural Extramedullary Spinal Tumor

Intradural extramedullary (IDEM) spinal tumors are generally benign neoplasms that occur within the dura mater but outside the spinal cord substance and usually treated with surgical excision. Symptoms of these tumors may varies with duration. This study denoted correlation between duration of preoperative motor deficit and early postoperative motor functional recovery that will help eventually to do more accurate assessment, counselling of the patients about surgical outcome and prognosis of IDEM spinal tumors. This prospective interventional study was carried out in the department of Neurosurgery, Dhaka Medical College and Hospital. A total N=49 patients of IDEM spinal tumor were included after taking informed written consent. A detailed history and thorough neurological examination were carried out. Pre and postoperative neurological function and motor deficit were evaluated by Modified Medical Research Council system (MRC) muscle grading. Follow-up was done at 30th postoperative day (POD). Data were collected and analyzed by SPSS – 24. Correlation between duration of preoperative motor symptoms and postoperative MRC grading was determined using Spearman’s rank correlation coefficient. Mean age of the patiesants was 41 ± 14.08 years with male predominance (55.1%). Schwannoma was the commonest tumor (42.8%). The commonest location was dorsal spine (46.9%). Pain was present in all (100%) patients, motor weakness in (97.9%), tingling/numbness in (69.4%), sphincter disturbance in 21 patients (42.9%). The mean duration of preoperative disease symptoms was 9.79 ± 7.46 months. According to MRC motor power grade, majority (83.7%) had improved at 30th postoperative day. Median (IQR) value of MRC motor power grade at 30th postoperative day was increased to 4(3-5) from preoperative grade 3(1-3). Spearman correlation model showed that duration of preoperative motor deficit had significant negative correlation with motor functional recovery at 30th POD (rs= -0.733, p <0.001). Preoperative duration of motor deficit and early postoperative motor functional recovery is significantly interrelated in patients with IDEM spinal tumors.

Lumbar endplate microfracture injury induces Modic-like changes, intervertebral disc degeneration and spinal cord sensitization – an in vivo rat model

BACKGROUND CONTEXTEndplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics. PURPOSEEstablish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord. STUDY DESIGN/SETTINGIn vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors. METHODSEP-injury was induced in 5 month-old male Sprague-Dawley rats L4–5 and L5–6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and μCT, and spinal cord SubP. RESULTSSurgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization. CONCLUSIONSSurgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions. CLINICAL SIGNIFICANCEThis rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

THE RESULT OF SURGICAL TREATMENT OF A LONG INTRAMEDULLARY SPINAL CORD TUMOR WITH SYRINGOMYELIA

A case of hospitalization of a 31-year-old patient due to pain in the lower back and thoracic spine, extending to the anterior surface of the thigh and accompanied by a lack of movement and sensitivity in the lower extremities, impaired pelvic organ function in the form of urinary incontinence and decreased libido is presented. Magnetic resonance imaging revealed an intradural-intramedullary long tumor at the level of VTh2-VTh3-VTh4-VTh5 vertebrae, with pronounced uneven expansion of the central canal of the spinal cord - syringomyelia throughout above and below the formation, uneven atrophy of the spinal cord substance. The patient underwent surgery to remove the tumor. Postoperative pathoanatomic examination confirmed the presumed histological diagnosis - astroependymoma. In the postoperative period, there was a partial recovery of motor and complete restoration of sensitive limb functions, regression of neurological deficit. On a repeated MRI gram 1 month after the operation, a total regression of syringomyelia above and below the levels of the removed tumor was determined.

Vincristine increased spinal cord substance P levels in a peripheral neuropathy rat model

Chemotherapy-induced peripheral neuropathy has an important impact on the quality of life of cancer patients. Vincristine-induced neuropathy is a major dose-limiting side effect. Symptoms of peripheral neuropathy are spontaneous pain, allodynia, and hyperalgesia. To analyze the contribution of substance P to the development of vincristine-induced mechanical allodynia/hyperalgesia, substance P levels in the rat spinal dorsal horn were analyzed after vincristine treatment. Mechanical allodynia/hyperalgesia was tested with the von Frey filaments 14 days after intraperitoneal (i.p.) administration of vincristine 0.1 mg/kg/day in rats. Vincristine-induced mechanical allodynia/hyperalgesia after day 14 was significantly inhibited by the neurokinin 1 receptor antagonist, aprepitant (20 mg/kg, s.c.). Immunohistochemistry showed that vincristine treatment significantly increased substance P expression (30.3% ± 2.4%) compared to saline treatment in the superficial layers of the spinal dorsal horn. Moreover, vincristine treatment significantly increased the substance P level in the spinal cord. These results suggest that vincristine treatment increases substance P in the spinal dorsal horn, and that aprepitant attenuates mechanical allodynia/hyperalgesia in vincristine-induced neuropathic rats.

Unilateral Epidural Targeting of Resiniferatoxin Induces Bilateral Neurolysis of Spinal Nociceptive Afferents.

This study modeled image-guided epidural drug delivery to test whether intraprocedural distribution of pre-injected contrast reliably predicts the neuroanatomical reach of resiniferatoxin-mediated nociceptive neurolysis. Swine (N = 12) received unilateral L4-S2 computed tomography fluoroscopy injections by a blinded neuroradiologist; 0.25 mL of contrast was pre-injected to confirm dorsal periganglionic targeting, followed by a 0.5-mL injection of 5 µg of resiniferatoxin/Tween80 or vehicle control. Epidural contrast distribution was graded according to maximum medial excursion. Spinal cord substance P immunostaining quantified the magnitude and anatomical range of resiniferatoxin activity. Periganglionic injection was well tolerated by all animals without development of neurological deficits or other complications. Swine were a suitable model of human clinical spinal intervention. The transforaminal approach was used at all L4 and 50% of L5 segments; the remaining segments were approached by the interlaminar route. All injections were successful with unilateral contrast distribution for all resiniferatoxin injections (N = 28). Immunohistochemistry showed bilateral ablation of substance P+ fibers entering the spinal cord of all resiniferatoxin-treated segments. The intensity of substance P immunostaining in treated segments fell below the lower 99% confidence interval of controls, defining the knockout phenotype. Substance P knockout occurred over a narrow range and was uncorrelated to the anatomical distribution of pre-injected contrast. Periganglionic resiniferatoxin/Tween80 induced bilateral ablation of spinal cord substance P despite exclusively unilateral targeting. These data suggest that the location of pre-injected contrast is an imperfect surrogate for the neuroanatomical range of drugs delivered to the dorsal epidural compartment that may fail to predict contralateral drug effects.

Experience medical rehabilitation of the patient after a comprehensive treatment of medulloblastoma of cerebellum with metastases in the shell and the substance of the spinal cord

The article describes the experience of medical rehabilitation of patients after a complex treatment of cerebellar medulloblastoma with metastases in the spinal cord membranes and substance. Substantiates the role of medical rehabilitation funds in correcting the effects of the disease, and cancer treatment, the essence of which is determined by the damage to the structure and function of various organs and systems. The most common effects of the three-treating medulloblastoma are postoperative deficits: ataxia and paresis; radiation myelopathy, polyneuropathy chemotherapy-induced, deformations of the skeletal system, reduced functional performance and adaptation. Actualized value of interdisciplinary interaction: oncologists, pediatricians, neurologists, orthopedists, medical rehabilitation specialists; phasing and integrated use of all available methods of rehabilitation. Presented personalized rehabilitation program to study techniques of individual lessons therapeutic exercises, therapeutic swimming, gidrokinezioterapii, procedures, motor praxis, training paretic muscles of the selected feedback, massage. It is shown that multimodal rehabilitation treatment of patients at high risk of being in remission, is effective in its action in assessing both subjective: improvement of health, emotional tone, sleep, increased appetite, and objective data: normalization of body weight, improving coordination and increasing the range of motion, increase muscle strength, strength endurance muscle corset. Currently, medical rehabilitation is an essential component of cancer patients routing.

Plasma pharmacokinetics and tissue and brain distribution of cisplatin in musk shrews.

Cisplatin induces nausea and emesis, even with antiemetic supportive care. To assess platinum exposure, which could activate nausea and emesis, we quantitated platinum in the brain and various organs, and hindbrain and spinal cord substance P, a key neuropeptide for the neuronal signaling of nausea and emesis. Musk shrews, a model species for nausea and emesis research, were dosed intraperitoneally with 20 mg/kg cisplatin and euthanized at up to 72 h after injection. Concentrations of platinum were quantitated in plasma ultrafiltrate, plasma, lung, kidney, combined forebrain and midbrain, hindbrain, and spinal cord by flameless atomic absorption spectrometry. Hindbrains and spinal cords were analyzed for substance P by immunohistochemistry after injection of 20 or 30 mg/kg. Plasma ultrafilterable platinum concentrations decreased rapidly till 60 min after dosing and then more slowly by 24 h. The concentrations of total platinum in both the fore- and midbrain and the hindbrain were similar at all time points and were at least 20-fold lower than plasma total platinum concentrations. There were no significant changes in substance P immunoreactivity after cisplatin dosing. Histology revealed damage to the renal cortex by 72 h after injection of cisplatin. This is the first study to examine platinum concentrations in musk shrews after administration of cisplatin and delineate substance P immunohistochemical staining in the hindbrain and spinal cord of this species. The platinum concentrations detected in the brain could potentially contribute to the neurological side effects of cisplatin, such as nausea and emesis.

The interaction of force and repetition on musculoskeletal and neural tissue responses and sensorimotor behavior in a rat model of work-related musculoskeletal disorders

BackgroundWe examined the relationship of musculoskeletal risk factors underlying force and repetition on tissue responses in an operant rat model of repetitive reaching and pulling, and if force x repetition interactions were present, indicative of a fatigue failure process. We examined exposure-dependent changes in biochemical, morphological and sensorimotor responses occurring with repeated performance of a handle-pulling task for 12 weeks at one of four repetition and force levels: 1) low repetition with low force, 2) high repetition with low force, 3) low repetition with high force, and 4) high repetition with high force (HRHF).MethodsRats underwent initial training for 4–6 weeks, and then performed one of the tasks for 12 weeks, 2 hours/day, 3 days/week. Reflexive grip strength and sensitivity to touch were assayed as functional outcomes. Flexor digitorum muscles and tendons, forelimb bones, and serum were assayed using ELISA for indicators of inflammation, tissue stress and repair, and bone turnover. Histomorphometry was used to assay macrophage infiltration of tissues, spinal cord substance P changes, and tissue adaptative or degradative changes. MicroCT was used to assay bones for changes in bone quality.ResultsSeveral force x repetition interactions were observed for: muscle IL-1alpha and bone IL-1beta; serum TNFalpha, IL-1alpha, and IL-1beta; muscle HSP72, a tissue stress and repair protein; histomorphological evidence of tendon and cartilage degradation; serum biomarkers of bone degradation (CTXI) and bone formation (osteocalcin); and morphological evidence of bone adaptation versus resorption. In most cases, performance of the HRHF task induced the greatest tissue degenerative changes, while performance of moderate level tasks induced bone adaptation and a suggestion of muscle adaptation. Both high force tasks induced median nerve macrophage infiltration, spinal cord sensitization (increased substance P), grip strength declines and forepaw mechanical allodynia by task week 12.ConclusionsAlthough not consistent in all tissues, we found several significant interactions between the critical musculoskeletal risk factors of force and repetition, consistent with a fatigue failure process in musculoskeletal tissues. Prolonged performance of HRHF tasks exhibited significantly increased risk for musculoskeletal disorders, while performance of moderate level tasks exhibited adaptation to task demands.

Extension MRI is clinically useful in cervical myelopathy

Cervical spine MRI with the neck in extension has been well described over the last 10 years, but its clinical value remains unknown. We performed extension imaging in 60 patients in whom the initial neutral study showed borderline cord compression. Images were assessed using a previously validated grading system for cord compression. Multiple linear and area measurements were also obtained. Images were scored blindly and randomly. Inter- and intra-rater variability were determined in a subset of 20 cases. Independent clinical assessment utilised the Ranwat criteria. For most parameters inter/intra-observer variance of kappa/ICC > 0.6 was highly satisfactory. Standard MR was poor at discriminating between patients with and without myelopathy (ROC analysis, area under the curve (AUC), 0.52). This was considerably improved with extension imaging (AUC, 0.60), or by using the change in compression score between neutral and extension studies. Most measurements were not helpful; however, the ratio of cord area/CSF area at the level of maximum compression on extended images was the best discriminator (AUC, 0.71), as well as the presence of T2 change in cord substance (AUC, 0.68). This is the first study to demonstrate added clinical value utilising extension MRI. In this cohort of difficult patients, when there was no T2 signal change in the cord, the presence of clinical myelopathy could only be predicted by utilising the data from extension imaging.

The effect of epidural morphine sponge in postoperative pain control after Microdiscectomy

Opiates such as morphine are one of the most effective classes of medication prescribed to treat both acute and chronic pain.They act to suppress pain through mu-receptor activation on primary afferent nerve fibers, dorsal horn neurons and supraspinal pain center neorons. When morphine is administered epidurally, it diffuses to the cord substance, producing analgesia [1],The aim of this study was to check the efficacy of this method for controling postoperative lumbar pain after microdiscectomy. In a randomized clinical trial, numbers of 100 patients were included into two equal groups due to low back radicular pain and underwent microdiscectomy. In study group, an absorbable gelatin sponge (Gelfoam) is contoured to the epidural space, placed in methylprednisolone acetate (40-80 mg), and then injected with 2 mg/ml morphine and control group received an absorbable gelatin, placed in methylprednisolone acetate (40-80 mg) and were injected with normal saline (5mL) as a placebo. The main outcome to be compared between trial and placebo groups were: Patient comfort rate in recovery room and ward, amount of analgesics used, postoperative ambulation time, post operative hospitalization days. The restlessness and agitation during recovery in study group was lower than control group. Mean systolic blood pressure increment was lower in morphine group. Only 6% of patients in study group compared to 98% in placebo group had either moderate or severe pain six hours after operation. Mean morphine dose used for study group was 10.75 mg compared to 21.4 mg among control group patients (P < 0.0001). Mean ambulation time was 2 days among study group patients compared to 2.6 days in control group. Mean hospitalization length was 4.7 and 7 days in study and control group respectively. By means of the technique assigned to the patient (an epidural morphine sponge) during Lumbar microdiscectomy the results were: Better controlled postoperative pain, early ambulation of patients and decreased hospitalization length.

Pro: It Is Safe to Proceed With Thoracoabdominal Aortic Aneurysm Surgery After Encountering a Bloody Tap During Cerebrospinal Fluid Catheter Placement

URING THE PAST 20 years, major advances in the intraoperative management of patients undergoing thoracoabdominal aortic aneurysm (TAAA) surgery have substantially reduced postoperative primary morbidity and mortality. At present, mortality rates after TAAA repair are estimated to be 5% to 10%, neurologic deficits 3% to 10%, renal failure 8% to 29%, and pulmonary complications 30% to 40%.1-4 Among the most feared complications of thoracic aortic aneurysm (TAA) and TAAA surgery are paraparesis and paraplegia, which are estimated to occur in 6% to 10% of patients who undergo TAA or TAAA repair. 5,6 Patients with these complications have a 20% greater risk of mortality than do patients without postoperative paraparesis or paraplegia. These patients, who are usually older, require intensive rehabilitation. A patient’s risk of postoperative paraparesis and paraplegia is determined by aneurysmal extent, acute dissection, cross-clamp time, preoperative renal dysfunction, previous aortic surgery, diabetes, and rupture.7 Improvements in TAAA repair procedures, including reduced cross-clamp time, distal aortic perfusion, and reattachment of intercostal arteries, have minimized critical ischemic times. Adjuncts such as cerebrospinal fluid (CSF) drainage, spinal cord monitoring, atrial femoral bypass, regional and systemic cooling, intrathecal papaverine, intraoperative use of naloxone, steroids and barbiturates, and the recognition and treatment of factors related to coagulopathy, have also been introduced. 8 The arterial circulation of the spinal cord consists of 2 interconnected sources: intrinsic and extrinsic. The intrinsic blood supply consists of a single anterior spinal artery (ASA), which courses along the ventral aspect of the cord and ultimately supplies the bulk of the cord substance through penetrating arteries, and paired posterior spinal arteries, which supply the remainder of the cord. This intrinsic circulation in turn receives its extrinsic blood supply via the radiculomedullary arteries, although the anatomic details of this supply vary among individuals. The principal extrinsic blood supply in the cervical and upper thoracic region comes from branches of the vertebral arteries; the thoracolumbar cord is supplied by intercostal and lumbar arteries, and the conus is supplied by the lateral sacral branches of the hypogastric vessels. There are 2 aspects of the spinal cord circulation that explain the risk of cord ischemia during TAAA repair. First, the diameter and continuity of the ASA vary along its length. Angiographic studies have shown that the ASA becomes extremely narrow cephalad to its anastomosis with the great radicular artery. Second, the human spinal cord is irregularly supplied by the radiculomedullary arteries because only few of them actually reach the cord substance. The thoracolumbar region is at the most risk for ischemic injury because this region is typically supplied by a single radiculomedullary artery, better known as the artery of Adamkiewicz or arteria radicularis magna. This artery has been shown to arise from T9 to T12 in about 75% of individuals. Because this area falls within the segment of the aorta that is clamped during reconstruction, clamping can compromise the blood supply to the cord. With proximal descending aortic cross-clamping, adequate spinal cord perfusion requires ASA patency, collateral circulation, and sufficient spinal cord perfusion pressure, defined as the difference between spinal artery pressure and CSF pressure. 9 During hypoxia and hypercarbia, autoregulation of spinal cord blood flow is lost and flow becomes linearly related to perfusion pressure. For this reason, adjuncts that decrease CSF pressure will increase spinal cord perfusion pressure. The rationale for using a CSF drain is based on experimental data showing that (1) CSF pressure increases during aortic clamping and (2) reducing CSF pressure improves spinal perfusion. Drenger et al 10 observed acute increases in CSF pressure immediately after applying the aortic clamp during TAAA repair. These increases were similar in patients with and without distal bypass and have been attributed to a sudden elevation of cerebral blood flow. The authors also observed a second peak

Biomehanicke karakteristike tkiva kicmene mozdine - osnov za razvoj modifikovane tehnike DREZ operacije

Mechanical properties of the spinal cord tissue--biological basis for the development of the modality of the DREZ surgery lesioning technique Succesful treatment of the chronic neurogenic pain of spinal cord and cauda equina injury origin remains a significant management problem. The mechanism of this pain phenomenon has been shown to be related to neurochemical changes that lead to the state of hypereactivity of the second order dorsal horn neurons. The DREZ surgery (Dorsal Root Entry Zone lesion), designed to destroy anatomy structures involved in pain generating thus interrupting the neurogenic pain mechanism, as a causative procedure in treating this chronic pain, has been performed by using different technical modalities: Radiofrequency (RF) coagulation technic, Laser, Ultrasound and Microsurgical DREZotomy technic. The purpose of the study was to assess the possibility for the establishment of the lesioning technic based on the natural difference in the mechanical properties between the white and gray cord substance. We experimentally deteminated mechanical properties of the human cadaveric cord white versus gray tissue for the purpose of testing possibility of selective suction of the dorsal horn gray substance as a DREZ lesioning procedure. Based on the fact of the difference in tissue elasticity between white and gray cord substance we established a new and simple DREZ surgical lesioning technique that was tested on cadaver cord. For the purpose of testing and comparing the size and shape of the DREZ lesion axchieved the DREZ surgery has been performed on cadaver cord by employing selective dorsal horn suction as a lesioning method. After the procedure cadaver cord underwent histological fixation and analysis of the DREZ lesions achieved. Our result revealed that the white cord substance with longitudinal fiber structure had four time higher dynamical viscosity than gray substance of local neuronal network structure (150 PaS versus 37.5 PaS) that provided possibility for the safe and selective suction of the gray substance of the dorsal horn. Technic includes incision of the dorsolateral sulcus according to Sindous Microsurgical DREZotomy technic than suction under visual control of the dorsal horn gray matter using succer adopted from the lumbar puncture nidle. Operative experimental testing and hystological analysis confirmed expected size and shape of the DREZ lesion performed by dorsal horn suction as DREZ lesioning technique. The utility, selectivity and safety of this technic has been provided by the natural mechanical properties of the cord tissue itself. Application of the Dorsal horn suction as a DREZ lesioning in humans confirmed this technic as a safe and reliable DREZ lesioning method.

A neutrophil elastase inhibitor (ONO-5046) reduces neurologic damage after spinal cord injury in rats.

In view of a cytoprotective effect of elastase inhibitor on chemokine-mediated tissue injury, we examined the neuroprotective effect of ONO-5046, a specific inhibitor of neutrophil elastase, in rats with spinal cord injury. Standardized spinal cord compression markedly increased cytokine-induced neutrophil chemo-attractant (CINC)-1 mRNA and protein. Their increases correlated with neurologic severity of injured rats. Immunohistochemically, CINC-1 protein was detected sequentially in vascular endothelial cells at 4 h, in perivascular neutrophils at 8 h, and in neutrophils infiltrating into cord substance at 12 h. Pretreatment with ONO-5046 (50 mg/kg) markedly ameliorated motor disturbance in injured rats, and reduced CINC-1 protein and mRNA expression. ONO-5046 also significantly reduced the increase of neutrophil accumulation or infiltration estimated by myeloperoxidase activity, and the extent of vascular permeability by Evans blue extravasation in the injured cord segment in comparison to control animals receiving vehicle. These results suggest that CINC-1 contributed to inflammation in rat spinal cord injury and ONO-5046 attenuated neurologic damage partly by blocking CINC-1 production of the chemoattractant, preventing neutrophil activation and vascular endothelial cell injury.

Spontaneous Herniation of the Thoracic Spinal Cord: A Case Report

Spontaneous herniation of the spinal cord is a rare disease entity in which spinal cord substance is herniated through a previously uninjured and/or untouched dura. It is a cause of myelopathy that is treatable but difficult to diagnose. We report the CT and MR findings of a case of spontaneous thoracic spinal cord herniation manifesting as ventrolateral protrusion of thoracic spinal cord through a dural defect.

Vascular Anatomy of the Spinal Cord and Classification of Spinal Arteriovenous Malformations

The arterial and venous anatomy of the spinal cord was described in terms of extrinsic and intrinsic contribution to the cord substance. Based upon anatomical location of an arteriovenous shunt, spinal arteriovenous malformations (AVMs) were classified into intramedullary AVM, perimedullary arteriovenous fistula (AVF) and dural AVF. This simple classification seems practical from the standpoint of endovascular and surgical treatments since it reflects anatomical differences in the shunt location, which is the target in either approach.

Invited commentary

Invited commentary

NK 3 receptor blockade prevents hyperalgesia and the associated spinal cord substance P release in monoarthritic rats

Previous studies in vitro have shown that NK 3 receptors exist on primary afferent terminals in rat spinal cord and mediate potentiation of the depolarisation-evoked substance P (SP) release. In the present study we have investigated the role of the NK 3 receptor-mediated SP release system in a model of inflammatory pain. Monoarthritis was induced in rats by unilateral injection of complete Freund's adjuvant (CFA); withdrawal latencies to a thermal stimulus were subsequently measured at various times following CFA. The CFA-treated paw displayed hyperalgesia as early as 4 h after CFA injection and hyperalgesia was maintained until day 4 but had disappeared by day 21. The thermal hyperalgesia was associated with an increase in basal SP release from spinal cord synaptosomes. The possible involvement of endogenous neurokinin B acting at NK 3 receptors was tested by using SB 223412-A [(S)-(−)- N-(α-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide hydrochloride], a novel, potent ( K i=30 nM) and selective ( K i>10 000 nM for NK 1 and NK 2 receptors), non-peptidic NK 3 receptor antagonist. In vitro SB 223412-A antagonised the potentiation of SP release produced by senktide in spinal cord synaptosomes. Administered systemically to monoarthritic rats (50 mg/kg, p.o., b.i.d., for 4 days), the NK 3 receptor antagonist SB 223412-A significantly reduced thermal hyperalgesia and normalised the basal release of SP from spinal cord synaptosomes. The data suggest that neurokinin B acting at NK 3 receptors that mediate SP release within the spinal cord play a role in inflammation. These NK 3 receptors may represent, therefore, appropriate targets in the therapy of inflammatory pain.

Effects of Halothane and Methoxyflurane on Regional Brain and Spinal Cord Substance P-Like and Beta-Endorphin-Like Immunoreactivities in the Rat

Effects of acute exposure (2 hr) to either 1.5% halothane or 0.5% methoxyflurane were investigated in the Sprague Dawley rat. Pituitary (PIT) and central nervous system (CNS) substance P (SP)-like and β-endorphin (β-end)-like immunoreactivities were evaluated immediately after anesthetic exposure (2 h), after righting reflex (4 h) or 24 hr postexposure (24 h). Only halothane significantly reduced SP-like immunoreactivity in olfactory bulbs in both the 2-h and 4-h groups. Halothane elevated SP-like immunoreactivity of hippocampus at all three time periods, and in the hypothalamus at 2 h. Both anesthetics significantly depleted thalamic concentrations of SP-like immunoreactivity. Methoxyflurane anesthesia resulted in a drastic decrease in SP-like immunoreactivity in PIT at all three time periods periods, while halothane elevated PIT concentrations of this peptide at 4 h. Both anesthetics significantly decreased β-end-like immunoreactivity in the olfactory bulbs and thalami at 2, 4, and 24 h. However, halothane alone significantly elevated β-end-like immunoreactivity in the spinal cord at 24 h. Halothane significantly elevated PIT β-end-like immunoreactivity at 2 and 24 h, while methoxyflurane significantly lowered it in the 4-h group, but elevated the levels of the same in the 24-h group. Brain stem β-end immunoreactivity were significantly reduced at 2 h by both anesthetics, and at 4 h by methoxyflurane. Results indicate that halothane and methoxyflurane may differ significantly in their actions on SP and β-end secreting neurons in the CNS.

Arteriovenous Malformation of the Cervical Spinal Cord with Unusual Drainage into the Cranial Cavity

A case of arteriovenous malformation of the cervical cord 20 years in duration, studied angiographically, using computerized tomography scans and magnetic resonance images, as well as findings at autopsy are presented. The malformation was fed by the right vertebral artery, which entered a giant saccular aneurysm-like structure located subdurally on posterior spinal cord surface, and terminated there. Plenty of vessels of various diameter were found in the spinal cord substance at this level (C4-C6). Blood flow drained via a grossly enlarged vein at the anterior spinal cord fissure into cranial cavity, where varicose posterior fossa veins could be clearly seen and a single vertebral artery was present.

Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain.

Numerous studies have implicated the primary afferent derived neuropeptide, substance P, which exerts its effects via the neurokinin-1/substance P receptor, in the transmission of nociceptive messages at the level of the spinal cord. Immunocytochemical studies demonstrate that the substance P receptor is concentrated in neurons of lamina I of the superficial dorsal horn. Since alterations in the number and distribution of the receptor may underlie persistent pain conditions, we have used immunocytochemistry to study the distribution of the receptor in two very different rat models of persistent pain: chronic inflammation, which is associated with increased levels of substance P, and sciatic nerve section, which is associated with decreased levels of substance P in the dorsal horn. Inflammation was produced by unilateral hindpaw injection of complete Freund's adjuvant. We report that there is an up-regulation of substance P receptor immunoreactivity in the superficial laminae of the dorsal horn in both injury models. The increase was found at all time points studied (up to one week after induction of inflammation and up to two weeks after sciatic nerve section). The increase in substance P receptor immunoreactivity was not only present in the medial part of the dorsal horn at segment L4, which is the region of input of the afferents from the hindpaw, but also in the lateral parts of the dorsal horn, and at segments rostral (L1) and caudal (S1) to the afferent input from the hindpaw. These results indicate that the up-regulation of the receptor is not predictable merely by the change in the concentration of substance P in the dorsal horn. Furthermore, the non-topographic up-regulation of substance P receptor in these different conditions may contribute to the central sensitization of dorsal horn nociceptors under conditions of persistent pain.