The spinal route--quo vadis?
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Analgesics↗
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Results for “Injections, Spinal”
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Spinal needle with depth guide: a new design for simplifying subarachnoid injections.
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Injections, Spinal↗
Direct administration of methotrexate into the central nervous system of primates. Part 2: Distribution of 3H methotrexate after intrathecal lumbar injection.
The kinetics of distribution of 3H methotrexate (3HMTX) in the central nervous system, plasma, and urine after intraventricular, lumbar percutaneous puncture, and spinal catheter injections were compared. Levels of 3HMTX in whole brain after lumbar percutaneous injection were 40 times less than after intraventricular injection. Injection of 3HMTX via a spinal catheter increased the level of 3HMTX in whole brain but this was still tenfold less than after direct intraventricular instillation. Also, it was found that a disproportionately high amount of 3HMTX was in the brain-stem-cerebellum region which would further reduce the concentration of methotrexate in the cerebral hemispheres. Both intraventricular and lumbar spinal catheter administration of 3HMTX produced 3HMTX levels greater than 10(-6)M (moles/kg wet weight) in spinal cord tissue as measured by 3H specific activity between 2 to 8 hours after injection. Administration by lumbar percutaneous puncture, however, rarely resulted in this suggested therapeutic level of 10(-6)M. Initial 3HMTX levels in plasma after lumbar percutaneous instillation was 24 times greater than after intraventricular or lumbar spinal catheter injections. This indicated significant and unavoidable extradural leakage after lumbar percutaneous puncture, which may account for the substantially lower levels of 3HMTX in the brain and spinal cord tissue. It is concluded that intraventricular instillation of methotrexate is the best route of administering the drug to achieve therapeutic levels of methotrexate in both whole brain and throughout the spinal cord.
Animals↗
Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse.
Intrathecal injection of N-methyl-D-aspartate (NMDA) induces a short duration hyperalgesia in mice. An inhibitor of nitric oxide synthase (NOS), N omega-nitro-L-arginine methyl ester (L-NAME), administered either systemically or intrathecally, blocked the NMDA-induced hyperalgesia. This effect was partially reversed by the NOS substrate, L-arginine. Intrathecal hemoglobin mimicked the effects of L-NAME. Intrathecal injection of the NO-donating compounds, sodium nitroprusside (SNP) and hydroxylamine, resulted in a hyperalgesia that lasted 3 h and was reduced by coadministration of hemoglobin. Thus, nitric oxide production appears to mediate NMDA-induced hypersensitivity and may contribute to other forms of centrally induced hyperalgesia.
Amino Acid Oxidoreductases↗
Spinal cord necrosis after intrathecal injection of methylene blue.
A 59 year old man had 6 ml of unbuffered methylene blue injected into the lumbar theca in an attempt to localise the source of cerebrospinal fluid rhinorrhoea. After injection of the dye he became shocked, and within the next few days he developed a mild paraparesis which subsequently progressed to a total paraplegia. The distribution of the spinal cord damage found at necropsy, eight and a half years after injection of the dye, is described and its relationship to the clinical picture discussed.
Cerebrospinal Fluid Otorrhea↗
Abolition of spinal motor disturbance by injections of dopamine receptor agonists, atropin and GABA into the caudate nucleus.
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Aminobutyrates↗
Tracing axons and axon collaterals of spinal neurons using intracellular injection of horseradish peroxidase.
Intracellular injection and subsequent histochemical localization of horseradish peroxidase have been used to stain the soma, dendrites, axons, and axon collaterals of spinalcervical tract neurons and unidentified dorsal horn neurons in the cat. This technique may be used in combination with the intracellular injection of Procion yellow to demonstrate by light microscopy connections between physiologically typed vertebrate neurons.
Animals↗
Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia.
A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli.
Animals↗
Effects of intramedullary injection of methiodal and lidocaine on spinal cords of dogs.
A solution of methiodal sodium (20%) and lidocaine HCl (0.20%) was given by intramedullary injection into the lumbar spinal cords of 12 anesthetized dogs (group I). Two control groups of 12 dogs each were subjected to needle placement only or were given 5% dextrose. The results showed that both solutions given by intramedullary injection caused severe spinal cord malacia and cavitation in 2 group I dogs and in 1 group III dog.
Animals↗
Descending course of primary afferent collaterals in the cat's spinal cord.
After injecting horseradish-peroxidase into the lower thoracic, lumbar and sacral spinal cord segments of cats, labelled perikarya were found in several spinal ganglia localized cranially to the site of injection. The segmental distance between the injection site and the rostralmost localized ganglion with labelled cells varied depending on the medio-lateral localization of the injection. The longest distance (10 segments) was achieved by medial injections. Primary sensory neurones with long descending collaterals belong to large ganglion cells.
Animals↗
Continuous Intrathecal Infusion of Nivolumab in Advanced Melanoma With Concomitant Leptomeningeal Disease: Efficacy, Safety, and Pharmacokinetics.
BACKGROUND AND OBJECTIVES: Prognosis of melanoma with leptomeningeal disease (LMD) is poor (median overall survival of 5.1 months). Intrathecal (IT) nivolumab appears safe, although its efficacy remains uncertain. We investigated the feasibility, safety, and efficacy of continuous IT nivolumab. METHODS: This was a retrospective analysis of 11 melanoma patients with progressive LMD (MelBase; NCT02828202) treated as part of the patients' care with continuous IT nivolumab administered through spinal (n = 10) or ventricular catheter (n = 1). RESULTS: Patients (5 women, median age 52) with Eastern Cooperative Oncology Group ≤1 (except for 1) and stable extracranial disease (except for 4) were treated over a median duration of 1.5 months and followed for 2.5 months. Seven presented symptomatic LMD. Primary tumors were mostly cutaneous (n = 8) and BRAF-mutated (n = 10). All patients had progressed on systemic immunotherapy; 7 had received brain radiotherapy (whole brain radiotherapy [n = 3]; stereotactic radiosurgery [n = 4]). Concomitant therapies included corticosteroids >10 mg (n = 5), intravenous nivolumab (first 3 months of IT therapy, n = 1), and targeted therapies (n = 7). The median overall survival was 2.5 months, with 3 patients surviving for more than a year. Reversible treatment-related adverse events occurred in 5 patients: meningoencephalitis (grade 3, n = 1), intracranial hemorrhage (grade 1, n = 1), intracranial hypotension (grade 2, n = 2; grade 1, n = 1). Baseline levels of nivolumab in the cerebrospinal fluid (CSF) were <2 µg/mL, even among patients with plasma detection. CSF concentrations of nivolumab at steady state varied from 36 to 97 µg/mL, with clearances of 4.3-15.7 mL/h. Next-generation sequencing identified CSF genomic profiles correlating with clinical progression in 4 patients. CONCLUSION: These findings warrant further trials on IT nivolumab.
Humans↗
Somatostatin causes vasoconstriction, reduces blood flow and increases vascular permeability in the rat central nervous system.
Using radiolabeled microspheres, spinal cord blood flow was measured after spinal subarachnoid injections of 3.1- to 12.5-nmol doses of somatostatin through either indwelling i.t. catheters or acutely inserted intervertebral needles. With either injection technique, somatostatin caused significant dose-dependent reductions in thoracic and lumbosacral blood flow that could be partially blocked by a 5-min preinjection of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)], which has previously been shown to block the hindlimb flaccidity produced by these doses of somatostatin in conscious rats. The duration of these blood flow changes were appreciably less in the rats injected through indwelling i.t. catheters. Somatostatin-induced reductions in spinal cord perfusion were accompanied by transient pressor responses, reduced cardiac output, 3-fold increases in spinal cord cerebrospinal fluid lactic acid concentrations and breakdown of the blood-spinal cord barrier, as reflected by significantly increased extravasation of [125I]bovine serum albumin. By 24 hr postinjection, a 12.5-nmol dose of somatostatin caused appreciable spinal cord cellular injury, as evidenced by significant elevations in cerebrospinal fluid concentrations of lactate dehydrogenase. After topical application to exposed pial vessels of the parietal cortex, comparable doses of somatostatin caused immediate intense dose-related arteriolar vasospasm and subsequent extravasation of the visible macromolecular tracer Evans blue dye. We conclude that somatostatin has significant vasoconstrictory effects on the blood vessels of the brain and spinal cord of the rat that must be recognized and appreciated when studying its neuropharmacological actions in vivo.
Animals↗
Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones.
1. The central action of botulinum toxin A (BTA) on the cholinergic transmission at Renshaw cells (RCs) and on the RC-induced inhibition of Ia inhibitory interneurones (IaINs) was studied in anaesthetized cats. BTA was administered by application directly into the spinal cord, injection into a ventral root (L7) and/or injection into the triceps surae (GS) muscle. 2. A direct application of BTA into the spinal cord led to a decrease of the early and the late response of RCs. 3. When the neurotoxin was injected into the GS muscle, the RC activity remained unaffected during the test period (33-46 h after application). 4. No effect appeared up to 10 h after an injection into the ventral root L7. 5. The RC-induced inhibition on IaINs, when tested in animals with local botulismus, remained intact during the test period. 6. From the present results it is suggested that on the spinal level the central action of botulinum toxin predominantly passes on the motoneurones.
Action Potentials↗
Intrathecally injected antibody can diffuse into spinal cord.
Antibody microinjection has been widely used to investigate the function of neuropeptides, but the capability of antibody to diffuse in the brain tissue has not been well characterized. The present study was conducted with an immunohistochemical method to determine if the anti-enkephalin serum injected intrathecally could diffuse into the spinal cord. Enkephalin immunoreactivity was observed in laminae I and II in slight amounts after 10 min, in moderate amounts after 30 minutes and very clearly after 60 min of the intrathecal injection of enkephalin antiserum. In addition, marked nonspecific staining was observed in the dorsal part but not in the ventral part of the white matter. These results indicate that antibodies injected intrathecally are capable of diffusing into the spinal cord within a time period of 10-60 min.
Animals↗
[Computer tomography of the cervical spinal canal following intrathecal enhancement: cervical CT myelography. Studies on technic and the initial results (author' transl)].
Computer tomography of the cervical spinal canal was carried out in 54 patients after the intrathecal injection of metrizamide (CT myelography). In 43 patients this was done after conventional myelography, in eleven it was the primary examination. In 32 patients the examination proved normal and in 22 abnormal. Correlation between the CT findings and conventional myelography was excellent. Quite small intraspinal structures both normal and abnormal, could be demonstrated. CT myelography is particularly valuable for determining the special relationships within the vertebral canal. The procedure can supplement and confirm conventional myelography, for instance round the foramen magnum. Under certain circumstances it may be regarded as the method of choice, since it is simpler for the patient and less likely to produce complications due to the contrast medium.
Adolescent↗
Spinal narcotics and respiratory depression.
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Aged↗
A selective and extremely potent antagonist of the neurokinin-1 receptor.
Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking. The behaviors elicited by physalaemin, septide and [Sar9, Met(O2)11]-SP were also reduced by co-administration of sendide. Large doses of sendide were needed to reduce the action of neurokinin A, D-septide, neurokinin B and eledoisin. The in vitro and in vivo pharmacological profile of sendide demonstrated that it is a selective and extremely potent antagonist of the neurokinin-1 receptor.
Amino Acid Sequence↗