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Systemic opioids produce analgesia in part by activating bulbospinal noradrenergic pathways. Spinally released norepinephrine (NE) has been suggested to produce analgesia in part by stimulating alpha2-adrenoceptors on cholinergic spinal interneurons to release acetylcholine (ACh). We hypothesized that this spinally released ACh would stimulate synthesis of(More)
The mechanisms supporting temporal processing of pain remain poorly understood. To determine the involvement of opioid mechanisms in temporal processing of pain, responses to dynamic noxious thermal stimuli and offset analgesia were assessed after administration of naloxone, a μ-opioid antagonist, and on a separate day, during and after intravenous(More)
BACKGROUND Opioids produce analgesia by direct effects as well as by activating neural pathways that release nonopioid transmitters. This study tested whether systematically administered opioids activate descending spinal noradrenergic and cholinergic pathways. METHODS The effect of intravenous morphine on cerebrospinal fluid and dorsal horn(More)
BACKGROUND Intradermal injection of capsaicin produces brief pain followed by hyperalgesia and allodynia in humans, and the latter effects are mediated by spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought to determine the effect of amitriptyline alone(More)
Anatomic studies have localized nitric oxide synthase (NOS) activity in the rat spinal cord dorsal horn and intermediolateral cell column. Behavioral and electrophysiologic studies suggest that N-methyl-D-aspartate (NMDA) stimulates nitric oxide synthesis in the dorsal horn. This report describes a novel bioassay to determine directly in vitro whether NMDA(More)
BACKGROUND Withdrawal thresholds in the paw are lower in younger animals, and incision further reduces these thresholds. The authors hypothesized that these differences result in part from changes in intrinsic electrophysiologic properties of large neurons. METHODS Using isolated whole dorsal root ganglion, current clamping was performed to determine the(More)
In rodents, acute exposure to opioids results in transient antinociception followed by longer lasting hypersensitivity to tactile or thermal stimuli, a phenomenon termed opioid-induced hyperalgesia. This hypersensitivity can be blocked or reversed by intrathecally administered cyclooxygenase inhibitors, including ketorolac, suggesting a role for spinal(More)
BACKGROUND Efficacy of analgesics varies with the type of pain. Little is known in this regard concerning labor pain, given the ethical barriers to study in humans and the lack of surrogate animal models. To address this, the authors classified and quantified spontaneous behaviors during labor and delivery in rats and examined the effects of a known(More)
Painful stimulation increases spinal cord norepinephrine (NE) in animals, and spinally released NE induces acetylcholine (ACh) release to cause analgesia. The purpose of this study was to determine the relationship between NE and ACh in cerebrospinal fluid (CSF) in sheep and humans during painful stimulation. CSF was sampled in anesthetized sheep before and(More)
Intraspinal administration of alpha 2 adrenergic agonists produces analgesia, but clinical application of these agents is limited by dose-dependent sedation and hypotension. Recently, neostigmine has been demonstrated to counteract hypotension in sheep and enhance antinociception to tail flick in rats from spinally administered alpha 2 adrenergic agonists.(More)