Antihyperalgesia by a2-GABAA Receptors Occurs Via a Genuine Spinal Action and Does Not Involve Supraspinal Sites
نویسندگان
چکیده
Jolly Paul, Gonzalo E Yévenes, Dietmar Benke, Alessandra Di Lio, William T Ralvenius, Robert Witschi, Louis Scheurer, James M Cook, Uwe Rudolph, Jean-Marc Fritschy and Hanns Ulrich Zeilhofer* Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland; Zurich Neuroscience Center (ZNZ), Zurich, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland; Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, USA; Laboratory of Genetic Neuropharmacology, McLean Hospital, and Department of Psychiatry, Harvard Medical School, MA, USA
منابع مشابه
Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord.
Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. Rats were injected with capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal thresho...
متن کاملGABAergic system for Ptychodiscus brevis toxin-induced depression of synaptic transmission elicited in isolated spinal cord from neonatal rats
The involvement of inhibitory transmitters for Ptychodiscus brevis toxin (PbTx)-induced depression of spinal synaptic transmission in neonatal rats was investigated. Stimulation of a dorsal root evoked monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root. The PbTx depressed the reflexes in a concentration-dependent manner and this depression was block...
متن کاملIs the pain modulatory action of 17β-estradiol in locus coeruleus of male rats is mediated by GABAA receptors?
Introduction: Estradiol is a neuroactive steroid, which is found in several brain areas such as locus coeruleus (LC). Estradiol modulates nociception by binding to its receptors and also by allosteric interaction with other membranebound receptors like glutamate and GABAA receptors. LC is involved in noradrenergic descending pain modulation. Methods: In order to study the effect of 17β-estra...
متن کاملGenuine antihyperalgesia by systemic diazepam revealed by experiments in GABAA receptor point-mutated mice.
Ionotropic gamma-aminobutyric acid (GABA(A)) receptors control the relay of nociceptive signals at several levels of the neuraxis. Experiments with systemically applied benzodiazepines, which enhance the action of GABA at these receptors, have suggested both anti- and pronociceptive effects. The interpretation of such experiments has been notoriously difficult because of confounding sedation. H...
متن کاملAnalgesia and unwanted benzodiazepine effects in point-mutated mice expressing only one benzodiazepine-sensitive GABAA receptor subtype
Agonists at the benzodiazepine-binding site of GABAA receptors (BDZs) enhance synaptic inhibition through four subtypes (α1, α2, α3 and α5) of GABAA receptors (GABAAR). When applied to the spinal cord, they alleviate pathological pain; however, insufficient efficacy after systemic administration and undesired effects preclude their use in routine pain therapy. Previous work suggested that subty...
متن کامل