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At least 19 recordsLinked to original sources

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↗

Similar behavioural effects of 5-hydroxytryptamine and substance P injected intrathecally in mice.

Intrathecal injection of 5-hydroxytryptamine (5-HT) or of substance P in mice elicited a behavioural syndrome consisting of reciprocal hindlimb scratching and biting or licking, directed towards the caudal parts of the body. 5-Hydroxtryptamine elicited more scratching than did substance P, which in turn caused a greater number of biting or licking responses. The 5-HT-induced responses were mimicked by 5,6-dihydroxytryptamine and inhibited by the 5-HT receptor blocker metergoline. The present findings indicate that 5-HT, injected intrathecally, may have similar effects as substance P in stimulating sensory pathways in the spinal cord.

5,6-Dihydroxytryptamine↗

Intrathecal injection of bombesin inhibits gastric acid secretion in the rat.

Bombesin (100-500 ng) injected intrathecally (T9-10) inhibited gastric acid secretion stimulated by pentagastrin and the GABAB agonist baclofen in urethane-anesthetized rats and basal gastric acid secretion in conscious, pylorus-ligated rats. Peptide action was dose-related, occurred within 30 min, and lasted for greater than 1 h. Bombesin-induced inhibition of pentagastrin-stimulated gastric acid secretion was not altered by cervical cord transection. Intravenous infusion of the monoclonal bombesin antibody 2A11 abolished intravenous bombesin (10 micrograms/kg.h)-induced 33% inhibition of gastric response to pentagastrin but did not alter intrathecal bombesin (200 ng)-induced 38% inhibition of gastric response to pentagastrin. The inhibitory effect of bombesin (200 ng) on pentagastrin-stimulated gastric secretion was reversed by bilateral adrenalectomy or removal of celiac and mesenteric ganglia. Intrathecal injections of rat calcitonin gene-related peptide, neuromedin B, neuromedin U, and the stable substance P analogue (pGlu5, MePhe8, MeGly9)-substance P(5-11) did not alter pentagastrin-stimulated gastric acid secretion. These results demonstrate that bombesin injected into the subarachnoid space of the spinal cord inhibits vagally stimulated and pentagastrin-stimulated gastric secretion in rats. Bombesin action is peptide specific, exerted at a spinal site, and expressed through the sympathetic nervous system.

Adrenalectomy↗

Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy.

Seven men and four women with symptomatic diabetic neuropathy were treated with methylcobalamin (2,500 micrograms in 10 ml of saline) injected intrathecally. Treatment was begun when patients had good metabolic control, as determined by measurements of plasma glucose and hemoglobin, and was repeated several times with a one-month interval between injections. Three patients were re-treated one year after the last intrathecal injection. Symptoms in the legs, such as paresthesia, burning pains, and heaviness, dramatically improved. The effect appeared within a few hours to one week and lasted from several months to four years. The mean peroneal motor-nerve conduction velocity did not change significantly. The mean (+/- SD) concentration of methylcobalamin in spinal fluid was 114 +/- 32 pg/ml before intrathecal injection (n = 5) and 4,752 +/- 2,504 pg/ml one month after intrathecal methylcobalamin treatment (n = 11). Methylcobalamin caused no side effects with respect to subjective symptoms or characteristics of spinal fluid. These findings suggest that a high concentration of methylcobalamin in spinal fluid is highly effective and safe for treating the symptoms of diabetic neuropathy.

Adult↗

Intrathecal injection of an oxytocin-receptor antagonist attenuated postnephrectomy natriuresis in the male rat.

We have previously shown that oxytocin (OT) is a major humoral mediator in postnephrectomy natriuresis. As immunoassayable OT has been demonstrated in the spinal cord, the aim of this investigation was to determine whether OT receptors in the spinal cord are also involved in this natriuresis. The experiments were performed on anesthetized male rats. Before acute unilateral nephrectomy, an oxytocin-receptor antagonist was injected intrathecally in the thoracolumbar region in rats. Postnephrectomy natriuresis was attenuated by this injection but not by intrathecal injection of artificial cerebrospinal fluid. Our results suggest that OT receptors within the spinal cord may influence the autonomic nervous regulation of renal function. In an additional experiment, intravenously infused hexamethonium did not prevent the adaptive natriuresis in the remaining kidney. We conclude that OT receptors in the spinal cord are involved in the postnephrectomy natriuresis, possibly as a component in the afferent signal pathway.

Animals↗

[Endogenous cortisol levels after intrathecal injection of triamicinolone acetonide in patients with neurological disease (author's transl)].

A single dose of 40 mg triamcinolone acetonide was injected intrathecally in 30 patients with multiple sclerosis and 20 with other neurological diseases. In 15 of them the endogenous cortisol level was determined on three successive days and their cerebrospinal fluid examined before the triamcinolone injection was given. Cortisol levels were then measured serially for another 15 days after the injection. Contrary to the response after intramuscular injection, the endogenous secretion of cortisol was not significantly depressed after intrathecal administration. The latter is, therefore, suggested in the treatment of inflammatory diseases of the central nervous system and its integuments, and for acute exacerbations of multiple sclerosis.

Humans↗

A single intrathecal injection of GABA permanently reverses neuropathic pain after nerve injury.

To investigate whether neuropathic pain is sensitive to spinal GABA levels, GABA was injected intrathecally after nerve injury and sensory behaviors were evaluated. Both thermal and tactile hypersensitivities were permanently reversed at the highest doses of GABA. However, if GABA was injected any later than 2-3 weeks after nerve injury, it was ineffective to prevent such hypersensitivity. This suggests that altered spinal GABA levels contribute to the induction phase of chronic neuropathic pain and that early intervention to restore GABA may prevent the development of that pain.

Animals↗

Behavioural effects of two dipeptides L-phenyl alanyl-L-arginine (Phe-L-Arg) and L-phenyl alanyl-D-arginine (Phe-D-Arg) after intracerebroventricular or intrathecal injections in mice.

L-phenylalanyl-L-arginine (Phe-L-Arg) and L-phenylalanyl-D-arginine (Phe-D-Arg), dissolved in a physiological saline were injected intrathecally into the lateral brain ventricle, and their behavioural as well as analgesic effects in mice were determined. It was found that a 100 nM dose of either peptide intracerebroventricularly (i.c.v.) injected induced an increase in the locomotor activity and a convulsive effect, whereas the same dose if injected produced a significant analgesic effect. It has been concluded that Phe-L-Arg and Phe-D-Arg have significant but different central effects in mice.

Analgesics↗

Differential modulatory effects of cholera toxin and pertussis toxin on pain behavior induced by TNF-alpha, interleukin-1beta and interferon-gamma injected intrathecally.

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro-inflammatory cytokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-alpha (TNF-alpha; 100 pg), interleukin-1beta (IL-1beta; 100 pg) and interferon-gamma (INF-gamma; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by TNF-alpha and INF-gamma administered intrathecally. But intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 microg) did not attenuate pain behavior induced by IL-1beta. On the other hand, intrathecal pretreatment with PTX further increased the pain behavior induced by TNF-alpha and IL-1beta administered intrathecally, especially at the dose of 0.5 microg. But intrathecal pretreatment with PTX did not affect pain behavior induced by INF-gamma. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important roles in modulating pain behavior induced by pro-inflammatory cytokines administered spinally. Furthermore, TNF-alpha, IL-1beta and INF-gamma administered spinally appear to produce pain behavior by different mechanisms.

Animals↗

Antinociceptive effects in mice after intrathecal injection of 5'-N-ethylcarboxamide adenosine.

When injected intrathecally in mice in a volume of 5 microliter, adenosine had no effect on tail-flick or hot-plate reaction latencies at dosages up to 1 mM concentration. There were no other behavioral effects observed either. Injecting 1 mM of the adenosine receptor agonist, 5'-N-ethylcarboxamide adenosine (NECA) caused both motor paralysis of the hind-legs with a duration of approximately 4 h and simultaneous antinociception. A slight weakness of the hindlegs, but a profound antinociceptive effect, was observed after the 100 microM dose only. After 10 microM, there was no effect on motor behavior but still a prolongation of the tail-flick and hot-plate reaction latencies. Pretreatment with the adenosine receptor antagonist theophylline attenuated the antinociceptive effect of NECA. Activation of spinal adenosine receptors thus appears to selectively elicit analgesia.

Adenosine↗

Repeated intrathecal injections of dezocine produce antinociception without evidence for neurotoxicity in the rat: a study of morphometric evaluation of spinal cord histology.

This study was designed to determine the antinociceptive and spinal cord histologic effects of a new agonist/antagonist opioid drug dezocine. This drug was injected intrathecally in rats at a dose of 50 or 125 micrograms twice daily for 14 days. The tail-flick test showed that the antinociceptive effect declined gradually, with no detectable effects by day 14. Quantitative histologic techniques and light and electron microscopy showed that neither dose, compared with vehicle, created any morphologic changes in the spinal cord that could be attributed to a neurotoxic or otherwise degenerative effect of the drug. In conclusion, dezocine is a drug that gives rise to sustained antinociceptive effects when administered intrathecally and causes no morphologic changes in the rat spinal cord that could be indicative of neurotoxic potential.

Analgesics↗

Intrathecal injection of high-dose meglumine amidotrizoate with complete recovery.

Rarely we are faced with accidental spinal injection of potentially toxic substances. We present 2 cases in which amidetrizoate, water-soluble ionic contrast medium, was accidentally injected intrathecally. Our treatment consisted of vigorous hydration and barbiturate coma. This report suggests that for water-soluble ionic contrast media increasing cerebrospinal fluid circulation by vigorous hydration may be as effective as spinal lavage in diminishing toxicity.

Adult↗

Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat.

R-phenylisopropyl-adenosine, which has an affinity for the adenosine A1 receptor higher than that for the A2 receptor, and N-ethylcarboxamide-adenosine, which has near equal affinity for the A1 and A2 receptors, were injected intrathecally into rats to evaluate differences in antinociceptive effect and motor impairment. Using the tail-immersion test, both compounds had antinociceptive effects. Motor function was evaluated during spontaneous movement in a free space. N-ethylcarboxamide-adenosine rapidly impaired motor function even after low intrathecal doses. R-phenylisopropyl-adenosine also induced motor impairment, but only after high intrathecal doses, and onset was much slower. These results suggest that the receptor selectivity of R-phenylisopropyl-adenosine is diminished at higher doses and that the motor impairment is an A2-receptor-mediated effect. A selective A1 receptor agonist, e.g., R-phenylisopropyl-adenosine, which produces a good antinociceptive effect without motor impairment, is more promising as a drug of possible use for the future treatment of clinical pain.

Adenosine↗

Intrathecal injection of HVJ-E containing HGF gene to cerebrospinal fluid can prevent and ameliorate hearing impairment in rats.

Hearing impairment, which is the most prevalent sensory deficit of human beings, needs a breakthrough in therapeutic technologies. One technology is the usage of a vector system to reach the inner ear, and another is by a therapeutic molecule. Here we developed a novel gene therapy strategy by combining hepatocyte growth factor (HGF) with hemagglutinating virus of Japan envelope (HVJ-E) vector. When HVJ-E containing human HGF gene was injected intrathecally into the cerebrospinal fluid via cisterna magna of rats, the vector reached the inner ear region, and human HGF gene expression was detected in the spiral ganglion cells (SGCs) of the inner ear. Expression of endogenous rat HGF and its receptor, c-Met, was also induced in SGCs by human HGF. Kanamycin treatment results in hearing impairment by inducing degeneration of hair cells (HCs) and apoptosis of SGCs in rats. By HGF gene transfer before kanamycin treatment, both loss of HCs and apoptosis of SGCs were prevented. Furthermore, hearing function, evaluated by auditory brainstem response, was maintained at a normal level. When HGF gene transfer was performed 2 wk after kanamycin treatment, hearing impairment was significantly recovered. These results indicate a novel and effective therapeutic strategy against sensorineural hearing impairment.

Animals↗

Synergistic behavioral effects of serotonin and tryptamine injected intrathecally in mice.

The endogenous compounds, serotonin (5-HT) and tryptamine (TA), have been found to alter function in the CNS, supporting the hypothesis that they serve as neurotransmitters. It is reported here that intrathecal injections of either 5-HT or tryptamine elicited similar behavioral syndromes consisting of caudally-directed biting, or licking and scratching. Serotonin was found to be considerably more potent than tryptamine. However, administration of both indoleamines produced synergistic interactions with respect to this behavioral syndrome. Administration of fluoxetine with either 5-HT or tryptamine potentiated the scratching behavior produced by either indoleamine, but failed to enhance the effect of an injection of 5-HT plus tryptamine. Administration of methysergide blocked the effects of both indolamines. The results are discussed in terms of a possible mechanism of the synergism between 5-HT and tryptamine.

Animals↗

Intrathecal injection of morphine for obstetric analgesia.

Intrathecal injection of morphine was used to provide obstetric analgesia in 20 primiparous women in labor. When the cervix was at least 3 cm dilated, morphine, 1 or 2 mg, was injected intrathecally. In all parturients, labor pains were completely relieved after 15-60 min and analgesia lasted as long as eight to 11 hours. The analgesia was not associated with any alteration of pin-prick sensation or motor power, and there was no change in the arterial blood pressure or heart rate. All infants were delivered vaginally by use of episiotomy annd a low forceps, except two infants of mothers in the 2 mg of morphine group who needed cesarean section. During the second stage of labor, analgesia was supplemented by lidocaine, 2 per cent, using local perineal infiltration in 14 parturients and pudendal block in two parturients, and by epidural block in four parturients. Nineteen of the 20 newborns cried immediately at birth, and had Apgar scores o 7-9 at 1 min and 8-10 at 5 min. During the first 24 hours of life, the neurobehavioral responses of all newborns were scored as normal. Systemic maternal side effects such as somnolence, nausea, vomiting, and itching occurred in a high proportion of the parturients. However, in the majority of cases, these side effects were mild. Only two parturients of the 2 mg morphine group complained of marked somnolence, itching, and vomiting, which persisted post partum; these were effectively reversed by the specific antagonist naloxone. The analgesic effect of intrathecal morphine can be attributed to its action on the opiate receptors in the substantia gelatinosa of the dorsal horn of the spinal cord. However, supraspinal effects of morphine cannot be excluded. The low lipid solubility of morphine can explain its slow onset and prolonged duration of action. Also, this will result in minimal systemic absorption of morphine, which protects the fetus and results in selective maternal analgesia.

Adolescent↗

Analgesia from the periaqueductal gray in the developing rat: focal injections of morphine or glutamate and effects of intrathecal injection of methysergide or phentolamine.

The aim of these experiments was to examine the changes in antinociception elicited by morphine or glutamate stimulation of the periaqueductal gray of the midbrain (PAG) during the postnatal development of the rat. Pups, aged 3, 10, and 14 days, were implanted with cannulas aimed at either the dorsal or the ventral aspect of the PAG, and glutamate (vehicle, 60 mM or 180 mM) or morphine (vehicle, 2 micrograms or 6 micrograms) was microinjected into one of those two sites. Pups were tested for analgesia against noxious thermal and mechanical stimuli. Morphine produced analgesia at 3 and 10 days of age only when administered to the ventral part of the PAG and the thermal noxious stimulus was tested. Conversely, analgesia induced by glutamate was seen at 3 and 10 days of age only when glutamate was given to the dorsal aspect of the PAG and the mechanical stimulus was used. In 14-day-old pups, both drugs produced analgesia against both types of noxious stimuli regardless of their site of administration within the PAG. Systemically administered naloxone attenuated the analgesic effects of both drugs when they were administered to the ventral PAG, but did not consistently attenuate the analgesic effect of either compound given to the dorsal aspect of the PAG. When either morphine or glutamate was injected into the ventral PAG, intrathecal injections of methysergide attenuated analgesia against the thermal stimulus to a significantly greater degree than the mechanical stimulus and intraspinal injection of phentolamine attenuated analgesia against the mechanical stimulus more potently. When glutamate was given to the dorsal PAG, analgesia against both stimulus types was significantly attenuated. These results indicate that the morphine- and glutamate-induced analgesia mediated by the PAG are developmentally differentiated. These ontogenetic differences most likely reflect differences in the mechanism of action by which these drugs produce analgesia when administered to the PAG, as well as neuroanatomical differences within the dorsal and the ventral regions of the PAG.

Aging↗

Intrathecal injection of capsaicin can be used as a behavioural nociceptive test in mice.

Intrathecal injections in mice of substance P (SP), capsaicin and kainic acid elicited a behavioural response similar to that caused by noxious stimulation. Although the agents have different mechanisms of action, they showed a similar response, consisting of biting, scratching and licking the caudal parts of the body. Activation of adenosine receptors in the spinal cord with 5-N-ethylcarboxamide adenosine (NECA) had no effect on the response to substance P or to kainic acid, but reduced the response to capsaicin. It is concluded that different substances, injected intrathecally, can be used to differentiate between pre- and postsynaptic induced nociceptive behaviour, and that this assay may be valuable in assessing central antinociceptive effects of various drugs, especially those affecting systems modulated by substance P.

Adenosine↗