[Oxygen therapy in spinal osteochondrosis].
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Female↗
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Results for “Injections, Spinal”
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[Successful treatment of metastases into the spinal canal in a patient with malignant melanoma].
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Adult↗
Pain management with spinal and epidural analgesia.
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Acute Disease↗
Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord.
The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII-X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.
Animals↗
Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions.
The effect of intrathecal administration of the novel tachykinin NK-1 receptor antagonist GR 82,334 has been tested in three reflexes which excite urinary bladder motility. GR 82,334 at 1 but not at 0.1 nmol/rat blocked the chemonociceptive micturition reflex induced by the topical application of capsaicin (4 micrograms/50 microliters) onto the urinary bladder. At the same dose proven effective in the chemonociceptive reflex, GR 82,334 did not affect either micturition reflex induced by bladder filling or the urinary bladder contraction induced by perineal pinching. These results suggest that, in urethane-anesthetized rats, specific stimuli applied in the periphery activate NK-1 receptors at spinal cord level facilitating urinary bladder reflex contractions.
Animals↗
Intrathecal application of cyproheptadine impairs locomotion in intact rats.
In intact adult rats, cyproheptadine, a 5-HT2 antagonist, administered intrathecally at the midlumbar segments was found to impair hindlimb locomotor movements during overground locomotion. These effects were dose-dependent; they varied from transient complete hindlimb paraplegia seen at doses of 300 microg/20 microl, to short-lasting trunk instability at doses of 100 microg/20 microl. After the return of overground locomotion, transient abduction of one of the hindlimbs was observed in some animals. These findings demonstrate that the blockade of 5-HT2 receptors affects locomotion in intact rats. Our results provide support for the hypothesis of serotonergic involvement in rat locomotion, which, so far, has been based mainly on the effects of 5-HT2 agonists on the recovery of locomotion in spinal rats.
Animals↗
Spinal NK2 receptors contribute to the increased excitability of the nociceptive flexor reflex during persistent peripheral inflammation.
The role of endogenous neurokinin A in changes in the excitability of spinal neurons during adjuvant-induced, peripheral inflammation was examined by determining the effect of a selective NK2 receptor antagonist, GR103537, on the nociceptive flexor reflex in rats. Intrathecal administration of GR103537 (1.4-14 nmol) dose-dependently attenuated the increased activity of the flexor reflex ipsilateral to the inflamed paw. The activity of GR103537 at NK2 receptors was confirmed by blockade of the facilitation of the reflex by neurokinin A but not substance P in normal rats. These results indicate that endogenous neurokinin A increases the excitability of spinal neurons during persistent peripheral inflammation.
Animals↗
Role of intracellular calcium in thermal allodynia and hyperalgesia in diabetic mice.
We examined the involvement of cytosolic calcium on thermal hyperalgesia and allodynia seen in diabetic mice. Tail-flick latencies at source voltages of a 50-W projection bulb to 35 and 50 V in diabetic mice were significantly shorter than those in non-diabetic mice. Tail-flick latencies at 35 and 50 V in diabetic mice were increased by pretreatment with ryanodine, which blocks Ca2+ release from Ca2+/caffeine-sensitive microsomal pools. On the other hand, intrathecal (i.t.) pretreatment with thapsigargin, which inhibits Ca2+ uptake into the inositol-1,4,5-trisphosphate-sensitive microsomal Ca2+ pool, decreased tail-flick latencies at 35 and 50 V in non-diabetic mice. Thus, it seems likely that thermal allodynia and hyperalgesia in diabetic mice may be due, in part, to the enhancement of intracellular calcium level in the spinal cord.
Animals↗
Effect of diabetes on pinacidil-induced antinociception in mice.
The antinociceptive effects of pinacidil, an adenosine triphosphate (ATP)-sensitive K(+)i (K(ATP)) channel opener, were examined using the tail-flick test in non-diabetic and diabetic mice. Pinacidil i.c.v. produced dose-dependent antinociception in both non-diabetic and diabetic mice. There was no significant difference between the antinociceptive effect of i.c.v. pinacidil in non-diabetic mice and diabetic mice. The i.t. administration of pinacidil also produced dose-dependent antinociception in both non-diabetic and diabetic mice, however, the antinociceptive effect of i.t. pinacidil in diabetic mice was significantly greater than that in non-diabetic mice. The antinociceptive effect of i.c.v. or i.t. pinacidil was significantly antagonized by i.c.v. or i.t. glibenclamide, a K(ATP) channel blocker in both non-diabetic and diabetic mice. In non-diabetic mice, the antinociceptive effect of i.c.v. or i.t. administration of pinacidil was significantly antagonized by beta-funaltrexamine, a mu-opioid receptor antagonist, 7-benzylidenenaltrexone, a delta1-opioid receptor antagonist, naltriben, a delta2-opioid receptor antagonist, and nor-binaltorphimine, a kappa-opioid receptor antagonist. In diabetic mice, the antinociceptive effect of i.c.v. pinacidil was significantly reduced by 7-benzylidenenaltrexone, naltriben, and nor-binaltorphimine. However, beta-funaltrexamine had no effect on antinociception induced by i.c.v. pinacidil in diabetic mice. On the other hand, the antinociceptive effect of i.t. pinacidil was significantly antagonized by beta-funaltrexamine, 7-benzylidenenaltrexone, naltriben, and nor-binaltorphimine in diabetic mice. These results indicated that pinacidil produced antinociception through the release of opioid peptides acting at mu-, delta- and kappa-opioid receptors in surpraspinal and spinal cord of non-diabetic mice. On the other hand, in diabetic mice, the antinociception-induced by pinacidil was mediated through the release of opioid peptides acting at delta- and kappa-opioid receptors supraspinally, whereas pinacidil produced antinociception through the release of opioid peptides acting at mu-, delta-, and kappa-opioid receptors spinally.
Animals↗
Plasma morphine concentration after intrathecal administration of low doses of morphine.
Plasma morphine concentration was measured in eight patients who received morphine 0.02 mg kg-1 intrathecally. The concentration was less than 0.5 ng ml-1 at 2 min and 10 min, 2 +/- 1 ng ml-1 at 30 min, 3 +/- 2 ng ml-1 at 1 h, 6 +/- 4 ng ml-1 at 3 h, 5 +/- 3 ng ml-1 at 12 h, 0.8 +/- 0.2 ng ml-1 at 24 h and less than 0.5 ng ml-1 at 36 h. The small plasma morphine concentrations we observed after intrathecal administration of morphine indicated that analgesia is a result of an action of morphine on opiate receptors, either spinal or cerebral.
Humans↗
CSF distribution of opioids in animals and man.
The CSF distribution of opioids after subarachnoid administration is important in determining therapeutic and undesirable side-effects. There are many factors which influence CSF distribution of opioids including the age, position, anatomy of the spinal column of the patient or animal, and the physico-chemical properties of the opioid solution and of the CSF. Opioids are cleared from their site of administration in CSF by three mechanisms: 1) uptake into the spinal cord, 2) diffusion through the dura and uptake into the blood, and 3) rostral-caudal CSF distribution. Physico-chemical factors such as lipid solubility, degree of ionization in the CSF and the baricity of the opioid solution are important in determining the rate of clearance by these three routes. Opioids which are highly lipid soluble, have high affinity for delta and/or kappa opiate receptor subtypes, and are largely non-ionized at physiologic CSF pH, would have optimal pharmacokinetic properties for subarachnoid administration. These properties would allow administration of a small dose of opioid which would be rapidly taken up into the spinal cord, thereby limiting CSF and vascular distribution to supraspinal brain regions.
Analgesia↗
Origin of 5-hydroxyindoleacetic acid in the spinl fluid.
5-Hydroxyindoleacetic acid applied intracisternally in cats does not appear in spinal fluid. Changes of 5-hydroxyindoleacetic acid concentration in the spinal cord are clearly reflected in the perfusate of the spinal subarachnoid space. Thus, 5-hydroxyindoleacetic acid in the spinal fluid originates from the spinal cord and reflects metabolic changes of 5-hydroxytryptamine in the spinal tissue, but not those in the brain.
Animals↗
The use of intrathecal midazolam in humans: a case study of process.
UNLABELLED: Early preclinical work demonstrated the potential role of spinal benzodiazepine pharmacology in regulating spinal nociceptive transmission. We review this preclinical activity and the evolving implementation of intrathecal midazolam in humans for pain management. Important elements in this development for use in humans are issues pertinent to safety and the preclinical reports that have increased our understanding of intrathecal midazolam toxicity. We seek to emphasize the time course of these studies and how they merged to provide enabling data that drove the clinical implementation. In the case of midazolam, we point to the potential issues that arose when preclinical safety data were unreasonably ignored and how consideration of preclinical safety data can serve to facilitate drug development by demonstrating reasonable safety profiles that document the minimal degree of potential risk to the patient. Issues that are of continuing relevance to the use of intrathecal midazolam, including issues of formulation and kinetics, are considered. IMPLICATIONS: The intrathecal use of midazolam has evolved over 20 years though a combination of preclinical and clinical investigations. We review the time course of this development to define critical elements that should be pursued in reducing the risk associated with the clinical use of a novel spinal drug.
Animals↗
Supraspinally mediated analgesic effect of antidepressant drugs.
Imipramine and amitriptyline, nonselective monoamine reuptake inhibitors, citalopram, selective serotonin reuptake inhibitor, and maprotiline, selective noradrenaline reuptake inhibitor, were tested after intracerebroventricular (icv) and intrathecal (it) administration in the rat writhing test to establish the role of the spinal and/or supraspinal structures in their effects. All drugs evoked dose-dependent analgesia after icv but not after it microinjections. The changes in the nociceptive behavior of rats pre-treated with antidepressants were not due to the non-specific influences of the drugs on the animals' gross behavior, as revealed by the open field test. The obtained results suggest that an antidepressant-induced analgesia mainly depends on the supraspinal effect with minor, if any, contribution from the spinal mechanisms.
Analgesics, Non-Narcotic↗
Platelet-activating factor reduces spinal cord blood flow and causes behavioral deficits after intrathecal administration in rats through a specific receptor mechanism.
Platelet-activating factor (PAF) is a phospholipid that has been implicated in the pathophysiology of delayed tissue damage after various forms of brain injury including ischemia, hypoxia and trauma. To examine its effects in the spinal cord, PAF was administered intrathecally to rats. PAF caused dose-dependent (30-100 nmol) decreases in spinal cord blood flow, in motor function or in survival. These actions were not reproduced by the biologically inactive precursor lyso-PAF or the enantiomer of this alkyl-phospholipid, which is not active at PAF receptors. PAF-induced changes were blocked completely by the selective receptor antagonist WEB 2170. Together, these findings demonstrate that PAF can alter spinal cord blood flow and motor function through a specific receptor mechanism, suggesting that this phospholipid may play a role in secondary tissue damage after spinal cord injury.
Animals↗
[The influence of intrathecal NMDA receptor antagonist on the isoflurane MAC and on the motor function].
The effect of intrathecal administration of NMDA (N-methyl-D-aspartate) receptor antagonists on the isoflurane MAC (minimum alveolar anesthetic concentration), and on the locomotor function, were studied in Wistar rats with catheters placed intrathecally. We determined the isoflurane MAC after the administration of either a competitive NMDA receptor antagonist, AP7 (0.044-132 nmole), or a non-competitive NMDA receptor antagonist, MK801 (0.3-90 nmole), as well as NMDA (0.068-204 nmole), and saline. AP7 (0.44-132 nmole) and MK801 (30-90 nmole) decreased the MAC. Intrathecal administration of NMDA reversed these decreases of MAC, but reversal effect is incomplete with AP7 132 nmole and MK801 90 nmole. In a locomotor dysfunction test, rats showed motor dysfunction with AP7 132 nmole (P < 0.05) and MK801 90 nmole (P < 0.05), but low doses did not exert these effects. Large doses of NMDA antagonist decreased the isoflurane MAC due to motor dysfunction, but low doses reduced the MAC without impairing motor function. We suspect that NMDA receptor antagonists play important roles in determining the isoflurane MAC in the spinal cord.
2-Amino-5-phosphonovalerate↗
Nociceptive responses to altered GABAergic activity at the spinal cord.
GABA agonists and antagonists were injected intrathecally at the spinal cord, to determine their effect on nociceptive thresholds. Tactile stimulation, applied against the flank by a medium diameter von Frey fiber (5.5 g force), elicited distress vocalizations after, but not before injection of the GABA antagonists, bicuculline MI or picrotoxin (0.25 and 1 microgram dosages). Vocalization threshold to tail shock was significantly reduced by bicuculline MI or picrotoxin. Tail flick withdrawal latency from radiant heat was not altered by GABA antagonists. The GABA agonist, muscimol, significantly elevated vocalization threshold to tail shock at a 5 micrograms dose. At a lower dose level (1 microgram), muscimol significantly reduced vocalization threshold to tail shock. Tail flick latency was significantly prolonged by the 5 micrograms dose of muscimol; however, flaccid paralysis of the hind limbs was also evident. Nociceptive thresholds were not altered by GABA or saline injection. These findings indicate that GABAergic activity contributes to the tonic modulation of nociception at the spinal cord.
Animals↗
Spinal CK2 regulates nociceptive signaling in models of inflammatory pain.
Casein kinase 2 (CK2) is a widely expressed protein kinase. Over the last several years a long list of protein substrates has evolved, many of which have proven or hypothesized roles in nociceptive signal transmission. However, CK2 has not itself been demonstrated to participate in nociception prior to this time. We set out to test the hypothesis that spinal CK2 regulates nociception using several pain models. Our first studies focused on the ability of the selective CK2 inhibitors 4,5,6,7-tetrabromobenzotriazole (TBBT) and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) to reduce formalin-stimulated pain behaviors in mice. Both phases of the response to subcutaneous formalin were strongly inhibited by intrathecal administration of TBBT or DRB in dose-dependent fashion. Likewise, using the complete Freund's adjuvant (CFA) model of chronic inflammatory pain, TBBT was observed to strongly reduce mechanical allodynia. The inhibition of spinal CK2 with either inhibitor did not, however, alter withdrawal latencies in the hotplate thermal pain model while intrathecal morphine was very effective. Immunohistochemical studies demonstrated all three known CK2 subunits, alpha, alpha' and beta to be expressed in spinal cord tissue as did real-time PCR experiments. While mRNA levels for each of the subunits was transiently enhanced after formalin or CFA hindpaw injection, overall spinal cord protein levels were not elevated in a sustained fashion. Our results indicate that CK2 participates in inflammatory nociception both in the acute and chronic phases. Simple changes in the abundance of spinal CK2 subunits do not likely underlie these phenomena, however.
Animals↗