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At least 73 records · Page 4Linked to original sources
PubMed1999

Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers.

BACKGROUND: Intrathecal adjuncts often are used to enhance small-dose spinal bupivacaine for ambulatory anesthesia. Neostigmine is a novel spinal analgesic that could be a useful adjunct, but no data exist to assess the effects of neostigmine on small-dose bupivacaine spinal anesthesia. METHODS: Eighteen volunteers received two bupivacaine spinal anesthetics (7.5 mg) in a randomized, double-blinded, crossover design. Dextrose, 5% (1 ml), was added to one spinal infusion and 6.25, 12.5, or 50 microg neostigmine in dextrose, 5%, was added to the other spinal. Sensory block was assessed with pinprick; by the duration of tolerance to electric stimulation equivalent to surgical incision at the pubis, knee, and ankle; and by the duration of tolerance to thigh tourniquet. Motor block at the quadriceps was assessed with surface electromyography. Side effects (nausea, vomiting, pruritus, and sedation) were noted. Hemodynamic and respiratory parameters were recorded every 5 min. Dose-response relations were assessed with analysis of variance, paired t tests, or Spearman rank correlation. RESULTS: The addition of 50 microg neostigmine significantly increased the duration of sensory and motor block and the time until discharge criteria were achieved. The addition of neostigmine produced dose-dependent nausea (33-67%) and vomiting (17-50%). Neostigmine at these doses had no effect on hemodynamic or respiratory parameters. CONCLUSIONS: The addition of 50 microg neostigmine prolonged the duration of sensory and motor block. However, high incidences of side effects and delayed recovery from anesthesia with the addition of 6.25 to 50 microg neostigmine may limit the clinical use of these doses for outpatient spinal anesthesia.

Adult↗
PubMedDate not supplied

Effect of systemic platelet-activating factor (PAF) on the rabbit spinal cord microcirculation.

Platelet-activating factor (PAF) is an endogenous phospholipid mediator with pro-inflammatory and vasoactive properties. Since PAF has been implicated in ischemic neuroinjury, we determined its effects on rabbit spinal cord microcirculation (SCM). Using laser-Doppler flow measurements, we monitored mean arterial pressure and SCM continuously on-line during and after i.v. infusion (1 min) of 0.5 nmol/kg of PAF (n = 20) and measured thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in arterial blood 1.5 min after the infusion. Responses were compared to those after indometacin pretreatment (4 mg/kg, n = 11). During the infusion, spinal cord blood flow (SCBF) decreased by 14 +/- 5% (P less than 0.05) paralleling the systemic hypotensive changes (17 +/- 5%, P less than 0.01) with no changes in vascular resistance (SCVR). However, immediately after termination of PAF infusion, SCVR decreased by 17 +/- 5% (P less than 0.01) while SCBF rapidly recovered. Plasma levels of both TXB2 and 6-keto-PGF1 alpha were significantly elevated. TXB2 release was correlated with the degree of hypotension during the PAF infusion (r greater than 0.72; P less than 0.05) while 6-keto-PGF1 alpha release correlated well with the decrease in SCVR during the infusion period (r greater than 0.64; P less than 0.05). Indomethacin blocked both the hemodynamic events and the eicosanoid release induced by PAF. Our data suggest that PAF modulates SCM through eicosanoid-mediated mechanism.

Animals↗
PubMedDate not supplied

Continuous spinal analgesia by means of micropumps[correction of micropumpus]: a report of 163 chronic pain patients.

Chronic pain in patients suffering from advanced cancer as well as unbearable chronic pain states depending on non-malignant pathology have always represented a test bench to verify results of advanced therapeutical programs as to more traditional approaches. The Authors present their experience resulting from longterm spinal infusion with peridural catheters connected to portable micropumps for the continuous administration of analgesic solutions. The availability of portable micropumps, a better understanding of spinal opioid receptors and advances in pharmacokinetics of opiate analgesics led in these years to a tremendous improvement of pain control possibilities and of the quality of life of patients.

Aged↗
PubMed2000

Clinical guidelines for intraspinal infusion: report of an expert panel. PolyAnalgesic Consensus Conference 2000.

Consensus guidelines developed by an expert panel are helpful to clinicians when there is variation in practice and lack of a firm evidence base for an intervention, such as intraspinal therapy for pain. An internet-based survey of practitioners revealed remarkable variation in practice patterns surrounding intraspinal therapy. This prompted an interdisciplinary panel with extensive clinical experience in intraspinal infusion therapy to evaluate the results of the survey, the systematic reviews of the literature pertaining to this approach, and their own clinical experience with long-term spinal infusions. The panel proposed a scheme for the selection of drugs and doses for intraspinal therapy, and suggested guidelines for administration that would increase the likelihood of a successful outcome. These expert panel guidelines were designed to provide an initial structure for clinical decision making that is based on the best available evidence and the perspectives of experienced clinicians.

Analgesics↗
PubMed1972

Depressor responses to spinal stimulation in the pithed rat.

1. Electrical stimulation of the spinal nerves in the pithed rat preparation produces a pressor response due to sympathetic vasoconstriction.2. When the vasoconstrictor effect of sympathetic stimulation is abolished by guanethidine or hexamethonium and the blood pressure is raised by noradrenaline infusion, spinal stimulation produces depressor responses or complex responses containing depressor components.3. Contractions of skeletal muscle caused by stimulation of motor nerves result in complex changes in blood pressure consisting of a pressor component due to clamping of muscle blood vessels and a secondary depressor phase due to functional hyperaemia.4. The depressor response is partly due to stimulation of cholinergic postganglionic fibres. The acetylcholine released, which causes vasodilatation, may be the overflow from neuromuscular junctions or ganglionic synapses.5. Stimulation of the nerves to the adrenal medulla causes release of adrenaline which has a vasodilator effect during noradrenaline infusion.

Adrenalectomy↗
PubMed1976

Reflex sympathetic tachycardia during intravenous infusions in chronic spinal cats.

The reflex tachycardia elicited by rapid intravenous infusions of a blood substitute was studied in 21 chronic cats with spinal sections at C8. All animals could breath spontaneously. The day after section the average resting heart rate (HR) and arterial pressure (AP) were 109 beats/min and 98/67 mmHg, respectively. Vagal blockade with atropine (0.5-0.7 mg/kg iv) was performed prior to each infusion, increasing the average HR To 127 beats/min. In 39 infusions in 21 cats the average increase in HR was 10 beats/min (range from -6 to +22 beats/min). A tachycardia was observed in all but five trials, four of which were obtained in two cats that subsequently responded with a tachycardia. In seven animals the neural circuit mediating the response was partially or totally interrupted by section of several thoracic dorsal roots (T1-T4 or T1-T6) and of the spinal cord at the inferior level of these sections (between T6 and T7). The tachycardia response was progressively reduced and finally abolished by these procedures. These experiments indicate that spinal neural mechanisms are likely to contribute to the phenomenon first described by Bainbridge.

Animals↗
PubMedDate not supplied

Management of progressive pain in a patient with intramedullary chordoma of the spine.

OBJECTIVES: The case here presented adequately reflects the difficulties involved in the treatment of pain in patients where the neuropathic component of pain predominates, and shows the different therapeutic steps that may be taken-from surgery and radiotherapy, to the administration of different drugs via the spinal route, to, finally, the presently little-used option of a direct intraventricular access. CONCLUSIONS: Spinal tumors are infrequent, but pose great difficulties for the management and control of the pain they cause. The utility of the spinal route as an early approach for the provision of adequate analgesia seems clear. However, it also appears to lose efficacy with time, and dose incrementing and/or the addition of drugs that enhance the analgesic action of morphine are not always effective. In such selected cases, the intraventricular route may constitute a useful alternative, allowing improved symptoms control with lower morphine doses, and the use of the system previously implanted for intrathecal spinal infusion.

Analgesics↗
PubMed1995

Axonal regeneration and physiological activity following transection and immunological disruption of myelin within the hatchling chick spinal cord.

Transections of the chicken spinal cord after the developmental onset of myelination at embryonic day (E) 13 results in little or no functional regeneration. However, intraspinal injection of serum complement proteins with complement-binding GalC or 04 antibodies between E9-E12 results in a delay of the onset of myelination until E17. A subsequent transection of the spinal cord as late as E15 (i.e., during the normal restrictive period for repair) results in neuroanatomical regeneration and functional recovery. Utilizing a similar immunological protocol, we evoked a transient alteration of myelin structure in the posthatching (P) chicken spinal cord, characterized by widespread "unravelling" of myelin sheaths and a loss of MBP immunoreactivity (myelin disruption). Myelin repair began within 7 d of cessation of the myelin disruption protocol. Long term disruption of thoracic spinal cord myelin was initiated after a P2-P10 thoracic transection and maintained for > 14 d by intra-spinal infusion of serum complement proteins plus complement-binding GalC or 04 antibodies. Fourteen to 28 d later, retrograde tract tracing experiments, including double-labeling protocols, indicated that approximately 6-19% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked peripheral nerve activity in paralyzed preparations, as well as leg muscle activity patterns typical of stepping in unparalyzed animals. This indicated that a transient alteration of myelin structure in the injured adult avian spinal cord facilitated brainstem-spinal axonal regrowth resulting in functional synaptogenesis with target neurons.

Animals↗
PubMed2004

Intrathecal ketorolac in dogs and rats.

This study was conducted to assess spinal safety of the cyclo-oxygenase inhibitor ketorolac in dogs and rats. Beagle dogs were prepared with lumbar intrathecal catheters and received continuous spinal infusions of 5 mg/ml ketorolac (N = 6), 0.5 mg/ml ketorolac (N = 8), or saline vehicle (N = 6) at 50 microl/h (1.2 ml/day) for 28 days. No systematic drug or dose-related changes were observed in motor function, heart rate, or blood pressure. Histological examination revealed a mild pericatheter reaction in all groups with no drug or dose related effect upon spinal pathology at the lumbar site of highest drug concentration. Cisternal CSF protein was elevated for all treatment groups at necropsy, and cisternal glucose was within normal range for all treatment groups, though three dogs displayed decreases in cisternal glucose. Significant reductions in hematocrit were noted, and increased incidence of gastric bleeding at necropsy was observed in animals receiving ketorolac. Intrathecal ketorolac kinetics revealed a biphasic clearance: t1/2 s = 10.3 and 53 min, respectively. After initiation of infusion (0.5 mg and 5 mg/ml/50 microl/h), lumbar CSF concentrations of ketorolac were 3.8 and 52.7 microg/ml, respectively. Bolus and continuous infusion of intrathecal ketorolac resulted in significant reduction of lumbar CSF PGE2 concentrations. In rats, with intrathecal catheters, four daily bolus deliveries of saline or ketorolac (5 mg/ml/10 microl) had no effect upon spinal histology or upon spinal cord blood flow. These data indicate that intrathecal ketorolac in two species at the dose/concentrations employed does not induce evident spinal pathology but diminishes spinal prostaglandin release.

Animals↗
PubMed1999

Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons.

This study concentrated on whether an increase in spinal nitric oxide (NO) diminishes inhibition of spinothalamic tract (STT) cells induced by activating the periaqueductal gray (PAG) or spinal glycinergic and GABAergic receptors, thus contributing to the sensitization of STT neurons. A reduction in inhibition of the responses to cutaneous mechanical stimuli induced by PAG stimulation was seen in wide dynamic range (WDR) STT cells located in the deep layers of the dorsal horn when these neurons were sensitized during administration of a NO donor, 3-morpholinosydnonimine (SIN-1), into the dorsal horn by microdialysis. In contrast, PAG-induced inhibition of the responses of high-threshold (HT) and superficial WDR STT cells was not significantly changed by spinal infusion of SIN-1. A reduction in PAG inhibition when STT cells were sensitized after intradermal injection of capsaicin could be nearly completely blocked by pretreatment of the dorsal horn with a NO synthase inhibitor, 7-nitroindazole. Moreover, spinal inhibition of nociceptive activity of deep WDR STT neurons elicited by iontophoretic release of glycine and GABA agonists was attenuated by administration of SIN-1. This change paralleled the change in PAG-induced inhibition. However, the inhibition of HT and superficial WDR cells induced by glycine and GABA release did not show a significant change when SIN-1 was administered spinally. Combined with our recent results, these data show that the effectiveness of spinal inhibition can be reduced by the NO/cGMP pathway. Thus disinhibition may constitute one mechanism underlying central sensitization.

Animals↗
PubMed2003

Lactoferrin enhances opioid-mediated analgesia via nitric oxide in the rat spinal cord.

Lactoferrin (LF) is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, we found that bovine milk-derived LF (BLF) produced analgesia via a mu-opioid receptor-mediated response in the spinal cord. However, the precise mechanism of this analgesic effect remains unclear. In this study, spinally applied BLF produced analgesia that was reversed by coadministration with a nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester, during phases 1 and 2 in the formalin test. Spinal coadministration of a mu-opioid receptor agonist, morphine, with a subeffective dose of BLF produced a much more highly potentiated analgesia than that produced by morphine alone during phases 1 and 2 in the formalin test. This potentiated analgesia by morphine with BLF was reversed by a mu-opioid receptor antagonist, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2, or by NG-nitro-l-arginine methyl ester. In the tail-flick test, continuous spinal infusion of morphine via an osmotic minipump over 6 days resulted in development of tolerance by day 4, but no tolerance of BLF was observed throughout the experiment. These results suggest that BLF acts as an enhancer of the spinal opioidergic system via an NO-mediated mechanism.

Analgesics↗
PubMed1993

Intrathecal baclofen for severe spasticity secondary to spinal cord injury.

OBJECTIVE: To evaluate the use of intrathecal baclofen for the treatment of muscle spasticity in patients with spinal cord injury. DATA SOURCES: A MEDLINE search was used to identify relevant and pertinent literature. Information was obtained from open-label clinical trials, abstracts, conference proceedings, and review articles. Index terms in the search included baclofen, spasticity, intrathecal drug infusion, spinal cord disease, and neurosurgery. DATA EXTRACTION: Studies were selected for review if they evaluated intrathecal baclofen in patients with spinal cord injury. Emphasis was placed on human studies published in the English language. Trials were reviewed by dosage regimen, therapeutic response, adverse effects, and complications. DATA SYNTHESIS: Thus far, intrathecal baclofen administration shows promise in the treatment of spasticity resulting from spinal cord trauma. Few complications and adverse effects have been reported. CONCLUSIONS: Muscle spasms and spasticity constitute a significant problem in spinal cord injuries, interfering with rehabilitation and leading to inconveniences and complications in these patients. Oral baclofen is the drug of choice for spasticity due to spinal cord trauma. It often is ineffective, however, because of the large dosages required to cross the blood-brain barrier and the subsequent appearance of central nervous system adverse effects. These adverse effects are not tolerated by many patients. Intrathecally administered baclofen has been approved by the Food and Drug Administration (FDA) for the treatment of spasticity in patients with spinal cord injury who are refractory to or cannot tolerate oral baclofen. It is intended for use only in implantable pumps approved by the FDA for the administration of baclofen into the intrathecal space. Intrathecal administration achieves high concentrations in the spinal cord with small dosages, thus reducing the incidence of central nervous system adverse effects. To date, approximately 350 patients with spinal cord injury have been treated with intrathecal baclofen. Reductions in spasticity have been demonstrated in both open-label and placebo-controlled trials. Patients also often make substantial gains in activities of daily living. Few adverse effects and complications have been reported. However, tolerance to the clinical effects of intrathecal baclofen has been reported. Further studies are needed to determine specific patient populations that may benefit most from intrathecal baclofen administration. Individual dosage ranges and follow-up care also need to be defined more completely. In addition, the question of whether tolerance detracts from long-term clinical benefits with intrathecal baclofen needs to be addressed.

Baclofen↗
PubMed1993

Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog.

The continuous spinal administration of baclofen has been shown to have therapeutic benefit in the management of spasticity in humans with neuraxial injuries. The present study systematically investigated the potential spinal neurotoxicity of continuous intrathecally-infused baclofen in dogs. Male beagle dogs were prepared with chronic lumbar intrathecal catheters connected to subcutaneously implanted infusion pumps. Three groups of dogs received 28 days of infusion of saline (vehicle: 1 ml/24 hrs; N = 10), 200 micrograms/ml/24 hrs baclofen (N = 10) or 2000 micrograms/ml/24 hrs baclofen (N = 10). A mild, dose-dependent anti-nociception and muscle weakness was observed. Independent assessment of spinal histopathology in dogs sacrificed and perfusion fixed at 28 days of treatment revealed a mild fibrotic reaction to the catheter, but there were no changes distinguishable from vehicle infused animals which could be ascribed to any dose of intrathecal baclofen. Cisternal CSF protein and cells in samples taken at sacrifice were also not different for the three groups. These findings with chronic intrathecally administered baclofen in this dog model jointly support the lack of toxicity of chronic intrathecal baclofen at concentrations up to 2000 micrograms/ml.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Spinal analgesics.

The important issues to be emphasized when considering the intrathecal administration of novel analgesics are their proven antinociceptive effect, safety (short- and long-term effects on the spinal cord and potential toxicities), stability in shelf solution and at body temperature by itself, or in combination with other drugs in spinal fluid, compatibility with a long-term spinal infusion pump, whether they are of sufficiently high potency and solubility to be used in the finite volume of an implanted infusion pump, and if a pharmaceutical company is willing to invest the immense resources needed for US Food and Drug Administration approval and subsequent commercial development.

Analgesics↗
PubMed2005

Inhibition of morphine analgesia by LPS: role of opioid and NMDA receptors and spinal glia.

Intraperitoneal (i.p.) injection of toxins, such as the bacterial endotoxin lipopolysaccharide (LPS), is associated with a well-characterized increase in sensitivity to painful stimuli (hyperalgesia) [Watkins LR, Maier SF, Goehler LE. Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states. Pain 1995;63:289-302. [53]] and a longer-lasting reduction in opioid analgesia (anti-analgesia) when pain sensitivity returns to basal levels [Johnston IN, Westbrook RF. Acute and conditioned sickness reduces morphine analgesia. Behav Brain Res 2003;142:89-97]. Here we show that this inhibition of morphine analgesia 24 h after a single i.p. injection of LPS involves mechanisms that contribute to illness-induced hyperalgesia and the development of analgesic tolerance to morphine. Specifically, morphine analgesia was restored if LPS was preceded by systemic administration of a non-competitive NMDA receptor antagonist (MK-801), spinal infusion of a glial metabolic inhibitor (fluorocitrate), or intracerebroventricular microinjection of an opioid receptor antagonist (naloxone). Morphine analgesia was also restored if MK-801 was administered after LPS. These results demonstrate that LPS recruits similar, if not the same mechanisms that reduce morphine tolerance following opiate administration: namely, stimulation of opioid and NMDA receptors and recruitment of spinal glia.

Animals↗
PubMed1996

Epidural and subarachnoid administration of opioids for nonmalignant pain: technical issues, current approaches and novel treatments.

As intraspinal opioid infusions are being offered to an increasing number of patients with chronic noncancer pain, technical considerations and complications have become important. For these technical considerations, there are points that are unclear and controversial and others that appear to be "minor" but, if missed, can lead to disastrous pump complications. Among the controversial areas are type of testing for a spinal infusion, method for needle placement in the spine, and type of pump. For the apparently minor considerations, important areas are attention to the method of puncture of the paraspinal fascia, anchoring of catheter, pump placement, and initial filling of the pump. As experience with these infusions is accumulated, and as the financial climate in medicine changes, the approaches to these techniques appear to be changing toward a general consensus. Recent scientific advances, both in newer analgesic substances and in innovative methods for intraspinal delivery of these substances, also are affecting these approaches.

Analgesia, Epidural↗
PubMed1996

A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia.

Tolerance to morphine analgesia is believed to result from a neuronal adaptation produced by continuous drug administration, although the precise mechanisms involved have yet to be established. Recently, we reported selective alterations in rat spinal calcitonin gene-related peptide (CGRP) markers in morphine-tolerant animals. In fact, increases in CGRP-like immunostaining and decrements in specific [125]hCGRP binding in the superficial laminae of the dorsal horn were correlated with the development of tolerance to the spinal antinociceptive action of morphine. Other spinally located peptides such as substance P, galanin, and neuropeptide Y were unaffected. Thus, the major goal of the present study was to investigate whether the development of tolerance to spinally infused morphine could be modulated by the blockade of dorsal horn CGRP receptors using the potent CGRP antagonist hCGRP(8-37). Indeed, cotreatments with hCGRP(8-37) prevented, in a dose-dependent manner, the development of tolerance to morphine-induced analgesia in both the rat tail-flick/tail-immersion and paw-pressure tests. Moreover, alterations in spinal CGRP markers seen in morphine-tolerant animals were not observed after a coadministration of morphine and hCGRP(8-37). These results demonstrate the existence of specific interaction between CGRP and the development of tolerance to the spinal antinociceptive effects of morphine. They also suggest that CGRP receptor antagonists could become useful adjuncts in the treatment of pain and tolerance to the antinociceptive effects of morphine.

Analgesics, Opioid↗
PubMed1998

[Pain therapy].

NEW OPIOID ANALGESICS: Progress in pain reliet has recently been achieved with the introduction of new opioid analgesics such as tramadol and the pediatric preparation of codeine phosphate as well as powerful long-release opioids which can be administered per os, or percutaneously for transdermal fentanyl. CO-ANALGESICS: Other drugs, mainly antidepressants and anti-convulsants, can be usefully combined with analgesics. New serotonin uptake inhibitors and anticonvulsants (gabapentin and lamotrigin) have the advantage of better tolerance. None of these drugs has marketing approval in France for their pain relieving effects. The same is true for clonidine and neostigmine which, after spinal infusion, potentialize opioids and for ketamine which can relieve neuropathy pain by dissociative anesthesia. NEW ANTI-MIGRAINE DRUGS: New drugs have been developed for specific types of pain such as migraine. The new "triptans" are tolerated better than sumatriptan and is reimbursed by the national social security. REFRACTORY NEUROPATHY PAIN: Indications for electrical stimulation techniques conducted in a neurosurgery unit have been identified. Stimulators may be implanted in spinal or supra-spinal localizations. REGULATORY ASPECTS: New legislation has reorganized health care for pain relief in France. The new texts take into consideration personnel training, the health care network and progress in therapeutics.

Adult↗