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Gamma aminobutyric acid (GABA) plays a major role in the central hyperexcitabilty associated with nerve damage. The precise antinociceptive actions mediated by GABA(A) receptor agonists remain unclear as previous studies have shown mixed results in neuropathic pain models. Thus, various drugs which modulate GABA(A) receptor function were tested in the rat(More)
The stimulation of extrasynaptic N-methyl-D-aspartate (NMDA) receptors triggers cell death pathways and has been suggested to play a key role in cell degeneration and neuron loss associated with glutamate-induced excitotoxicity. In contrast, synaptic NMDA receptors promote neuronal survival. One mechanism through which extrasynaptic NMDA receptors damage(More)
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by a polyglutamine expansion within the Ataxin-2 (Atxn2) protein. Purkinje cells (PC) of the cerebellum fire irregularly and eventually die in SCA2. We show here that the type 2 small conductance calcium-activated potassium channel (SK2) play a key role in control of normal PC(More)
Calcium-activated potassium channels are attractive targets for the development of therapeutics for overactive bladder. In the current study, we addressed the role of calcium-activated potassium channels of small (SK; K(Ca)2) and intermediate (IK; K(Ca)3) conductance in bladder function pharmacologically. We identified and characterized a novel positive(More)
The anticonvulsant retigabine has previously been reported to inhibit bladder overactivity in rats in vivo but the mechanism and site of action are not known. In the present study we investigated the effect of retigabine in isolated rat bladder tissue. Bladders from Sprague-Dawley rats were cut transversally into rings and mounted on an isometric myograph.(More)
Neuropathic pain conditions can encompass a diverse constellation of signs and symptoms consisting of sensory deficits, allodynia and hyperalgesia. Animal models of neuropathic pain have enabled the identification of key pathophysiological changes occurring within nociceptive pathways as a result of injury, and serve an invaluable role for preclinical(More)
Neuronal cholinergic transmission is a prerequisite for proper CNS function. Consequently, disturbance of this system is associated with a number of pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, schizophrenia and ADHD. Consequently, drug discovery efforts have spurred considerable research endeavours into identifying(More)
Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII-polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10(More)
Spiroergometric examination with defined work loads and permanent records of the common circulatory and metabolic values were carried out on a group of healthy adults and one wheelchair occupant, using a fixed wheelchair simulator with lever propulsion, which was connected to an ergometer. Comparative studies were performed in three different seat positions(More)
RATIONALE Neuropathic pain is associated with a number of disease states of diverse aetiology that can share common pathophysiological mechanisms. Antiepileptic drugs modulate ion channel function and antidepressants increase extracellular monoamine levels, and both drug classes variously attenuate signs and symptoms of neuropathic pain. Thus,(More)