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PubMed2002

Chronic muscle pain induced by repeated acid Injection is reversed by spinally administered mu- and delta-, but not kappa-, opioid receptor agonists.

Opioids are commonly used for pain relief clinically and reduce hyperalgesia in most animal models. Two injections of acidic saline into one gastrocnemius muscle 5 days apart produce a long-lasting bilateral hyperalgesia without associated tissue damage. The current study was undertaken to assess the effects of opioid agonists on mechanical hyperalgesia induced by repeated intramuscular injections of acid. Morphine (mu-agonist), [D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin (mu-agonist; DAMGO), 4-[((alpha)R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (delta-agonist; SNC80), or (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cylcohexyl]-benzeneacetamide hydrochloride (kappa-agonist; U50,488) were administered intrathecally to activate opioid receptors once hyperalgesia was developed. Mechanical hyperalgesia was assessed by measuring the withdrawal thresholds to mechanical stimuli (von Frey filaments) before the first and second intramuscular injection, 24 h after the second intramuscular injection, and for 1 h after administration of the opioid agonist or vehicle. Morphine, DAMGO, and SNC80 dose dependently increased the mechanical withdrawal threshold back toward baseline responses. The reduction in hyperalgesia produced by morphine and DAMGO was prevented by H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) and that of SNC80 was prevented by naltrindole. U50,488 had no effect on the decreased mechanical withdrawal thresholds. Thus, activation of mu- and delta-, but not kappa-, opioid receptors in the spinal cord reduces mechanical hyperalgesia following repeated intramuscular injection of acid, thus validating the use of this new model of chronic muscle pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2005

Iatrogenic (para-) spinal abscesses and meningitis following injection therapy for low back pain.

Low back pain is often treated with paraspinal injections of analgesics and steroids. Infectious complications of these techniques are rare but they can potentially hold high risks for the patients. History and clinical data of all patients admitted to a neurological unit suffering from community acquired purulent meningitis were prospectively analyzed during an 8 year interval (1992 and 2000) with special regard to the previous medical history. One hundred and twenty eight patients were included in the study. Eight out of 128 patients (6.25%) had a history of single or repeated paravertebral (4/8), facet-joint (2/8), peridural (1/8) or spinal (1/8) injections 2-21 days before admission to the hospital. In six out of eight patients either Staphylococcus aureus (4/8) or coagulase-negative staphylococci (2/8) were found in the cerebro spinal fluid (CSF), in two patients no causative organism was detected. One patient died, three survived with sequel. Repeated paraspinal, peridural or spinal injections with analgesic drugs in combination with corticosteroids hold a risk for parameningeal inoculation of bacteria resulting in paraspinal, spinal, and epidural abscesses or meningitis. The absolute frequency of these complications may be rare but they are responsible for a considerable proportion of community acquired purulent CNS infections.

Adolescent↗
PubMed1992

Mechanism of extension of spinal anaesthesia by extradural injection of local anaesthetic.

We have examined the effect of extradual injection of 0.5% bupivacaine or normal saline on the progression of spinal anaesthesia in 28 patients undergoing Caesearean section. Three groups were studied. Subarachnoid anaesthesia was established in all patients. Group A (n = 10), the control, received no extradural injection for 20 min. Group B (n = 9) received extradural bupivacaine 10 ml and group C (n = 9) received extradual saline 10 ml 5 min after the subarachnoid injection. Sensory levels were compared at 5-min intervals and extension of the block was found to be similar in groups B and C and significantly faster than the control (P < 0.05). The quality of anaesthesia and incidence of adverse effects was similar for all three groups. We conclude that the mechanism of extension of spinal anaesthesia by extradural injection of local anaesthesia is largely a volume effect.

Adult↗
PubMed2006

Acute but not chronic stimulation of glial cells in rat spinal cord by systemic injection of lipopolysaccharide is associated with hyperalgesia.

We have analyzed development of mechanical hyperalgesia after repeated systemic lipopolysaccharide (LPS) injections and correlated these findings with stimulation of astrocytes and microglia in spinal cord. Male Lewis rats received a single or seven intraperitoneal injections of LPS. Mechanical hyperalgesia was measured as rat hindpaw withdrawal thresholds (PWTs). We observed that a single LPS injection elicited a specific change of PWTs while stimulated spinal glial activation was identified by immunoreactivities of specific markers, ED1, P2X4 receptor, endothelial monocyte activating polypeptide II (EMAP II) and glial fibrillary acidic protein (GFAP), respectively; multiple LPS treatments induced tolerance to mechanical hyperalgesia, whereas expression of ED1 and GFAP were further increased. In conclusion, we have demonstrated that the number of activated spinal glial cells was increased as an acute effect of LPS correlating with increased sensitivity to mechanical stimulation. However chronic exposure to LPS can develop a tolerance to mechanical hyperalgesia despite ongoing signs of CNS glial activation.

Animals↗
PubMed2001

Roentgenographic evaluation of ossification and calcification of the lumbar spinal canal after intradiscal betamethasone injection.

There have been reports of lumbar spinal canal ossification and calcification after triamcinolone intradiscal injection therapy. Our objective was to observe the roentgenographic changes after betamethasone intradiscal injection therapy for lumbar disc diseases. The subjects were 183 patients (498 discs; 130 men and 53 women) who underwent discography and betamethasone intradiscal injection therapy and were followed for a mean of 5 years and 7 months. Ossification and calcification appeared de novo (three patients, three discs) or enlarged (four patients, five discs) in the outer layer of the posterior annulus fibrosus or posterior longitudinal ligament in eight discs among seven patients (3.8%). The incidence and degree of ossification and calcification in our patients were significantly lower than those reported in previous studies, and a long time elapsed before ossification and calcification appeared or enlarged. Intradiscal injection of betamethasone did not appear to confer any incremental relative risk for lumbar spinal canal ossification and calcification based on review of follow-up roentgenographs.

Adolescent↗
PubMed1997

Autonomous neural axis formation by ectopic expression of the protooncogene c-ski.

The ski oncogene was originally isolated as an avian retroviral gene with the ability to induce quail embryonic cells to differentiate into muscle. Mice containing a chicken c-ski transgene exhibit postnatal hypertrophy of skeletal muscle. Xenopus ski (Xski) protein is maternal and present throughout early development. We show that overexpression of Xski RNA in Xenopus embryos results in the cell-autonomous induction of secondary neural axis formation. Injection of Xski RNA into prospective endodermal cells resulted in the formation of an ectopic neural tube-like structure and cells derived from the injected blastomeres populated the spinal cord. Injected Xski RNA was able to induce neural-specific gene expression directly in ectodermal explants in the absence of the expression of mesodermal markers. The widespread distribution of ski protein in the early gastrula embryo including the dorsal animal region supports a role for ski in neural axis formation in vivo.

Amino Acid Sequence↗
PubMed1990

Abnormal distribution of phosphorylated neurofilaments in neuronal degeneration induced by kainic acid.

An abnormal distribution of phosphorylated neurofilaments is present in some human neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. This study reports the changes of phosphorylated neurofilaments observed in rat spinal cord after intrathecal injection of kainic acid. This receptor agonist of excitatory amino acid produces abnormal phosphorylation of neurofilaments in the cell body and proximal neurites of degenerating neurons. These immunocytochemical modifications observed 2 and 10 days after injections are predominantly located in ventral horn neurons. This study indicates that one of the neuronal responses to excitatory amino acid toxicity is the pathological distribution of phosphorylated neurofilaments in affected neurons. Pathological findings are comparable to those observed in neurodegenerative diseases such as amyotrophic lateral sclerosis.

Animals↗
PubMed1991

Preparative surgery enhances the direct spinal actions of three injectable anaesthetics in the anaesthetized rat.

In this study we have investigated the influence of preparative surgery on the potency with which a range of injectable anaesthetics depressed nociceptive withdrawal reflexes in anaesthetized, spinalized rats. Drug effects were compared on 2 different preparations, each requiring differing degrees of preparatory surgery. Recordings were made in each case of unitary motoneurone responses to controlled noxious stimuli. The dose-dependent effects of the general anaesthetics alpha-chloralose (20-80 mg/kg i.v.) and alphaxalone/alphadolone (0.5-2 mg/kg) and of the dissociative anaesthetic ketamine (0.5-16 mg/kg) were studied. When the degree of surgical intervention was increased, the reflex response to a uniform mechanical pinch stimulus was facilitated. This enhanced response was more susceptible to the reflex depressant actions of all the compounds studied.

Action Potentials↗
PubMed1991

Changes in cerebrospinal fluid pressure and spinal cord perfusion pressure prior to cross-clamping of the thoracic aorta in humans.

Little is known about what influences cerebrospinal fluid pressure (CSFP) during anesthesia prior to aortic cross-clamping (AXC). Therefore, this study measured the effect of anesthetic induction, of various drugs administered during the course of surgery prior to AXC, and of hemodynamic changes on CSFP, and calculated spinal cord perfusion pressure (SCPP = mean arterial pressure [MAP] - CSFP) in 11 patients undergoing surgery on the descending thoracic aorta. A lumbar drainage catheter was placed to facilitate drainage of CSF and to measure CSFP. Anesthesia was induced with fentanyl, 50 micrograms/kg, and midazolam, 1 mg, using a pancuronium-metocurine mixture for neuromuscular blockade. Data were collected prior to and after (1) anesthetic induction, (2) mannitol to augment diuresis, (3) sequential use of sodium nitroprusside (SNP) and isoflurane (ISO) to lower MAP by 20%, (4) drainage of spinal fluid, (5) intrathecal injection of papaverine (IP), and (6) AXC. Statistical comparisons of recorded data were made using the least squares mean method and Friedman test. Linear regression was used to test for correlation between CSFP and hemodynamics. Anesthetic induction affected neither hemodynamics nor CSFP. Mannitol significantly increased heart rate, central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and CSFP (P less than 0.05). SNP or ISO altered neither CVP, PCWP, CO, nor CSFP, which remained elevated at the postmannitol infusion level. ISO, unlike SNP, caused a significant decrease in SCPP (P less than 0.005). Subsequent drainage of 20 mL of CSF improved SCPP (P less than 0.05). IP did not have any effect on hemodynamics or CSFP. CSFP showed a strong correlation with CVP (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed2004

Role of prostaglandin receptor subtype EP1 in prostaglandin E2-induced nociceptive transmission in the rat spinal dorsal horn.

It has been indicated that prostaglandin E2 (PGE2) and the receptor for PGE2 (EP receptor) are key factors contributing to the facilitated generation of nociception. This study was designed to investigate the roles of PGE2 and EP1 receptors in the spinal cord in the nociceptive transmission, using behavioral and intracellular calcium ion concentration ([Ca2+]i) assays and in situ hybridization. Experiments were conducted on Sprague-Dawley rats. In behavioral assays, withdrawal thresholds to mechanical stimuli were evaluated using von Frey filament. The effect of an intrathecally administered selective EP1 antagonist, 6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)-bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid (ONO-8711), on the intrathecal PGE2-induced hyperalgesia was examined. In [Ca2+]i assays, we measured [Ca2+]i in the dorsal horn of spinal cord slices and examined the effects of PGE2 and ONO-8711 perfusion on the [Ca2+]i changes. In situ hybridization using EP1 digoxigenin probe was performed on the slice sections of the lumbar spinal cord and bilateral L4 and L5 dorsal root ganglions (DRGs). Mechanical hyperalgesia was observed after intrathecal PGE2 administration. Intrathecal administration of ONO-8711 attenuated the PGE2-induced mechanical hyperalgesia in a dose- and time-dependent manner. Perfusion of ONO-8711 markedly suppressed PGE2-induced [Ca2+]i increment in laminae II-VI in dorsal horn of the spinal cord slice. Moreover, in situ hybridization revealed EP1 hybridization signals in the DRG neurons, but not in the spinal cord. The results of this study suggested that spinal PGE2 activates the EP1 receptors existing on the central terminals of primary afferents, subsequently increasing in [Ca2+]i in the spinal dorsal horn, which are involved in the mechanisms of spinal PGE2-induced nociceptive transmission.

Afferent Pathways↗
PubMed1998

Intrathecal administration of the adenosine A1 receptor agonist R-phenylisopropyl adenosine reduces presumed pain behaviour in a rat model of central pain.

Effects of intrathecally (i.t.) administered R-phenylisopropyl adenosine (R-PIA), an adenosine A1 receptor agonist, on presumed pain behaviour were assessed in a rat model of chronic central pain. Spinal cord injury was induced photochemically via laser irradiation of the spinal cord after intravenous injection of erythrosin B in rats. The chronic allodynia-like behaviour that developed in some animals was studied. R-PIA (3 and 10 nmol), injected i.t. reduced the mechanical and cold allodynia-like symptoms as tested with von Frey filaments and ethyl-chloride spray, respectively. No side effects were observed. The effect of R-PIA was significant for up to 5 h and was reversed by theophylline, an adenosine receptor antagonist.

Adenosine↗
PubMed2004

Polyphosphoramidate gene carriers: effect of charge group on gene transfer efficiency.

Cationic polymeric carriers have been widely used for gene delivery. However, the structure-function relationship, especially the effect of charge groups of cationic polymeric carriers on the transfection activity, is poorly understood. To examine this important parameter, a series of cationic polymers, polyphosphoramidates (PPAs) with an identical backbone, same side chain spacer, similar molecular weights but different charge groups containing primary to quaternary amino groups (PPA-EA, PPA-MEA, PPA-DMA and PPA-TMA, Figure 1) were synthesized. The DNA-binding affinity of these four PPAs increased in the order of PPA-EA PPA-MEA>PPA-DMA>PPA-TMA. Particle size and zeta potential of four different types of PPA/DNA nanoparticles did not show significant correlation with PPA structure. These PPAs did not show significant buffering capacity within pH 5-7, even though transfection mediated by PPA-EA was the only one that seemed to be limited by endolysomal escape. Endocytosis of DNA mediated by PPAs was also similar (17-22%) for all four PPAs. However, the transfection efficiency of these PPAs varied significantly. In vitro transfection efficiency of PPAs decreased in the order of PPA-EA>PPA-MEA>PPA-DMA approximately PPA-TMA. Nanoparticles with PPA-EA containing primary amino groups gave the highest transfection efficiency in cell lines at the charge ratios from 6/1 to 20/1 (+/-). Matching the trend of transfection efficiency observed in vitro, PPA-EA mediated the highest transgene expression, comparable to that of polyethylenimine, in the spinal cord following intrathecal injection of the nanoparticles. These results establish that PPA gene carriers with primary amino group side chains are more potent than those with secondary, tertiary or quaternary amino groups in vitro and in the intrathecal gene delivery model.

Animals↗
PubMedDate not supplied

Rehabilitation of spasticity and related problems in childhood cerebral palsy.

Spasticity is one part of the upper motor neuron syndrome, but it is a widespread problem in cerebral palsy; it is debilitating, affects function and can lead to musculoskeletal complications. Significant advances have occurred in antispasticity management (and related musculoskeletal problems) in children with cerebral palsy during the past 5-10 years. Botulinum toxin A has been the most outstanding treatment advance; it is relatively long-lasting, easy to administer, reversible, has a favourable side-effect profile and is highly useful for focal spasticity. There is an emerging role for intrathecal baclofen in Australia. Despite being available and practised in North America for years, selective dorsal rhizotomy has not been popular in Australia. The use of orthopaedic surgery has significantly altered in recent years. There is still a place for oral drug treatment, including some newer agents and the potential for combination treatment with other modalities. The role of physical therapy in defining disability, assessing function, undertaking biomechanical assessment and providing mobility aids/casting/orthoses and motor training/stretching exercises is critical for the success of medical and surgical interventions. From an Australian perspective, the purpose of the present review is to provide a critical review of therapies available for spasticity associated with childhood cerebral palsy.

Administration, Oral↗