BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins.

Iron (Fe) is an essential element for most organisms which must be obtained from the local environment. In the case of pathogenic bacteria, this fundamental element must be acquired from the fluids and tissues of the infected host. A variety of systems have evolved in bacteria for efficient acquisition of host-bound Fe.

Bilateral eyelid necrosis as a complication of pseudomonal septicaemia.

We present a case of bilateral eyelid necrosis as a result of Pseudomonas aeruginosa infection. This is a rare condition that occurs only in neutropenic patients. It may be unilateral or bilateral and requires aggressive management with correction of the neutrophil count, local debridement and systemic antibiotic therapy.

Nerve injury induces plasticity that results in spinal inhibitory effects of galanin.

Galanin is a 29-amino-acid neuropeptide that has been implicated in the processes of nociception. This study examines the effect of exogenous galanin on dorsal horn neurone activity in vivo in the spinal nerve ligation (SNL) model of neuropathic pain. SNL rats but not naive or sham-operated rats exhibited behaviour indicative of allodynia.

Inhibition of release of neurotransmitters from rat dorsal root ganglia by a novel conjugate of a Clostridium botulinum toxin A endopeptidase fragment and Erythrina cristagalli lectin.

Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types. Here we report that a catalytically active derivative (termed LH(N)/A) of the type A neurotoxin from Clostridium botulinum has been coupled to a lectin obtained from Erythrina cristagalli to form a novel conjugate. This conjugate exhibits an in vitro selectivity for nociceptive afferents compared with the anatomically adjacent spinal neurons, as assessed using in vitro primary neuronal culture systems to measure inhibition of release of neurotransmitters.

Neuropharmacologic targets and agents in fibromyalgia.

Chronic widespread pain is a primary feature of fibromyalgia and is a symptom that is poorly managed in many patients. In addition, patients often experience fatigue, sleep disturbances, and anxiety. Its etiology is largely unknown.

Nerve injury-induced changes in opioid modulation of wide dynamic range dorsal column nuclei neurones.

In the present study we investigated the effects of spinal morphine on the electrically and naturally evoked responses of gracile nuclei neurones in a rat model of neuropathy, induced by the tight ligation of lumbar L5/6 spinal nerves. Two weeks after surgery, animals were prepared for electrophysiological recordings and neuronal responses were characterised to a range of controlled natural (brush, low- and high-intensity von Frey filaments, heat 45 degrees C) and peripheral electrical stimuli. Morphine (0.

Neurobiology of neuropathic pain: mode of action of anticonvulsants.

Anticonvulsants are widely used for the treatment of neuropathic pain. Here we review the evidence for a number of peripheral and central changes after nerve injury that may provide a basis for the mechanisms of action of anticonvulsant therapies. The roles of sodium channels, calcium channels, and central glutamate mechanisms are emphasized as the main targets for anticonvulsant drugs in neuropathic pain states.

A combination of gabapentin and morphine mediates enhanced inhibitory effects on dorsal horn neuronal responses in a rat model of neuropathy.

Background: Peripheral nerve damage can result in severe, long-lasting pain accompanied by sensory deficits. This neuropathic pain remains a clinical problem, and effective morphine analgesia is often limited by intolerable side effects. The antiepileptic gabapentin has recently emerged as an alternative chronic pain treatment.

Amino acids are still as exciting as ever.

Glutamate is probably the most important excitatory transmitter in the vertebrate central nervous system. Its multiple functional roles in the brain and spinal cord make therapeutic manipulation of these systems fraught with difficulties. There has, however, been recent progress in pharmacological manipulations of NMDA receptor subtypes and non-NMDA receptors, and understanding of the roles of NAAG, that promise rapid advances in pain control.

Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy.

Neuropathic pain, due to peripheral nerve damage, can include allodynia (perception of innocuous stimuli as being painful), hyperalgesia (increased sensitivity to noxious stimuli) and spontaneous pain, often accompanied by sensory deficits. Plasticity in transmission and modulatory systems are implicated in the underlying mechanisms. The Kim and Chung rodent model of neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of the sciatic nerve and reproducibly induced mechanical and cold allodynia in the ipsilateral hindpaw over the 14 day post-operative period.

Effects of ethosuximide, a T-type Ca(2+) channel blocker, on dorsal horn neuronal responses in rats.

Plasticity in transmission and modulatory systems are implicated in mechanisms of neuropathic pain. Studies demonstrate the importance of high voltage-activated Ca(2+) channels in pain transmission, but the role of low voltage-activated, T-type Ca(2+) channels in nociception has not been investigated. The Kim and Chung rodent model of neuropathy [Pain 50 (1992) 355] was used to induce mechanical and cold allodynia in the ipsilateral hindpaw.

The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury.

1. Adenosine (ADO) receptor activation modulates sensory transmission in the dorsal horn. Little is known about the circumstances underlying release of the purine.

Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy.

Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical and heat) stimuli were recorded. The systemic effects of three N-methyl-D-aspartate receptor (NMDA) antagonists, ketamine (1-10 mg/kg), memantine (1-20 mg/kg) and MK-801 (0.

Electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal nerve ligation model of neuropathy.

Background: Changes in the inhibitory activity mediated by gamma-aminobutyric acid (GABA) and glycine, acting at spinal GABAA receptors and strychnine-sensitive glycine receptors, are of interest in the development of neuropathic pain. There is anatomic evidence for changes in these transmitter systems after nerve injuries, and blocking either GABAA or glycine receptors has been shown to produce allodynia-like behavior in awake normal animals.

Methods: In this study, the possible changes in GABAergic and glycinergic inhibitory activity in the spinal nerve ligation model of neuropathic pain were studied by comparing the effects of the GABAA-receptor antagonist bicuculline and the glycine-receptor antagonist strychnine in neuropathic rats to their effects in sham-operated and nonoperated control rats.

Electrophysiological studies on the role of the NMDA receptor in nociception in the developing rat spinal cord.

The present study investigated the effects of spinally applied N-methyl-D-aspartate (NMDA) antagonists 2-amino-5-phosphonovaleric acid (AP5) and ketamine on convergent neurones in the deep dorsal horn of rats, in vivo at different postnatal ages (P) 14, 21, 28, and 56 days. AP5 inhibited the primary afferent fibre input, the C fibre, post-discharge and windup evoked responses in a dose-dependent manner at each age, and was significantly more effective in the pups than adult rats (P<0.03 at 100-microg dose).

Peripheral administration of low pH solutions causes activation and sensitisation of convergent dorsal horn neurones in the anaesthetised rat.

This is the first study to examine the effects of peripheral administration of acid on the activity of dorsal horn neurones in vivo. Extracellular recordings from convergent neurones revealed increases in neuronal activity evoked by administration of low pH solutions into the peripheral receptive field. Threshold for activity ranged from pH 5.

An excitatory role for 5-HT in spinal inflammatory nociceptive transmission; state-dependent actions via dorsal horn 5-HT(3) receptors in the anaesthetized rat.

The involvement of 5-HT(3) receptor mediated modulation of formalin and carrageenan induced inflammatory transmission was investigated. The effects of the selective 5-HT(3) receptor antagonist ondansetron on the electrically evoked responses of dorsal horn neurones in normal animals were compared to those following carrageenan. The effect of pre-treatment on the formalin response was also studied.

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers.

Role of Ca2+-permeable non-NMDA glutamate receptors in spinal nociceptive transmission.

The functional role of Ca2+-permeable non-NMDA receptors in spinal nociceptive processing was investigated using joro spider toxin (JSTx), a selective blocker of these receptors. JSTx 0.25 and 1 microg administered spinally produced a significant facilitation of the C-fibre evoked response and post-discharge, but not the A-fibre response, of dorsal horn neurones recorded in adult rats.

Different increase in C-fibre evoked responses after nociceptive conditioning stimulation in sham-operated and neuropathic rats.

Mechanisms of neuropathic pain are not clear. Recently we showed long-term potentiation (LTP) of wide dynamic range (WDR) neurones after electrical conditioning stimulation of the sciatic nerve in normal rats. In this study we investigated the effects of the same conditioning on both the evoked responses of WDR cells and on vital signs in neuropathic rats.