A5055625141- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Botulinum Toxin and Related Neurological Disorders
- Migraine and Headache Studies
- Musculoskeletal pain and rehabilitation
- Pain Management and Placebo Effect
- Pain Management and Opioid Use
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Nerve injury and regeneration
- Pharmacological Effects of Natural Compounds
- Neurotransmitter Receptor Influence on Behavior
- Ion channel regulation and function
- Anesthesia and Pain Management
- Trigeminal Neuralgia and Treatments
- Veterinary Pharmacology and Anesthesia
- Olfactory and Sensory Function Studies
- Ion Channels and Receptors
- Sympathectomy and Hyperhidrosis Treatments
- Cannabis and Cannabinoid Research
- Cancer Treatment and Pharmacology
- Pain Management and Treatment
- Ophthalmology and Eye Disorders
- Memory and Neural Mechanisms
- Hormonal and reproductive studies
University of Arizona
2014-2024
Ithaka Harbors
2020-2022
Syneos Health (United States)
2018-2020
American Headache Society
2019-2020
New York Proton Center
2020
Carolina Headache Institute
2019
Clinical Solutions
2017
Arizona Science Center
2013
Philadelphia University
2008
Marymount University
2004
Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to agents. Unlike DNA, LNA/DNA copolymers were not degraded readily blood serum and cell extracts. However, like the capable activating RNase H, an important mechanism action. In contrast phosphorothioate-containing oligonucleotides, isosequential LNA analogs did cause...
Introduction Galcanezumab is a humanized monoclonal antibody binding calcitonin gene-related peptide, used for migraine prevention. Methods A global, double-blind, 6-month study of patients with episodic was undertaken 915 intent-to-treat randomized to monthly galcanezumab 120 mg (n = 231) or 240 223) placebo 461) subcutaneous injections. Primary endpoint overall mean change from baseline in headache days. Key secondary endpoints were ≥50%, ≥ 75%, and 100% response rates; days acute...
Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such has been hypothesized be the result of an aberrant expression and function sodium channels at site injury. Here, we show intrathecal administration specific antisense oligodeoxynucleotides (ODN) tetrodotoxin (TTX)-resistant channel, NaV1.8, resulted in time-dependent uptake ODN by dorsal root ganglion (DRG) neurons, selective "knock-down" reduction slow-inactivating, TTX-resistant...
Relief of pain is rewarding. Using a model experimental postsurgical we show that blockade afferent input from the injury with local anesthetic elicits conditioned place preference, activates ventral tegmental dopaminergic cells, and increases dopamine release in nucleus accumbens. Importantly, preference associated increased activity midbrain neurons blocked by antagonists injected into The data directly support hypothesis relief produces negative reinforcement through activation mesolimbic...
Although injury-induced afferent discharge declines significantly over time, experimental neuropathic pain persists unchanged for long periods. These observations suggest that processes initiate may differ from those maintain such pain. Here, the role of descending facilitation arising developing plasticity in rostral ventromedial medulla (RVM) initiation and maintenance was explored. Tactile thermal hypersensitivity were induced rats by spinal nerve ligation (SNL). RVM lidocaine blocked...
The nonopioid actions of spinal dynorphin may promote aspects abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that might mediate effects sustained opioids was explored. Possible antinociceptive were evaluated intrathecal administration [d-Ala<sup>2</sup>,<i>N</i>-Me-Phe<sup>4</sup>, Gly-ol<sup>5</sup>]enkephalin (DAMGO), an μ agonist. Rats infused with DAMGO, but not saline, demonstrated...
Many clinical case reports have suggested that sustained opioid exposure can elicit unexpected, paradoxical pain. Here, we explore the possibility (1) opioid-induced pain results from tonic activation of descending facilitation arising in rostral ventromedial medulla (RVM) and (2) presence such manifests behaviorally as antinociceptive tolerance. Rats implanted subcutaneously with pellets or osmotic minipumps delivering morphine displayed time-related tactile allodynia thermal hyperalgesia...
Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking prodynorphin gene were studied for sensitivity non-noxious and noxious stimuli, before after induction experimental neuropathic pain. Prodynorphin knock-out (KO) had normal responses acute stimuli a mild increased some stimuli. After nerve ligation (SNL), both wild-type (WT) KO demonstrated decreased thresholds innocuous mechanical...
Neurons in the rostroventromedial medulla (RVM) project to spinal loci where neurons inhibit or facilitate pain transmission. Abnormal activity of facilitatory processes may thus represent a mechanism chronic pain. This possibility and phenotype RVM cells that might underlie experimental neuropathic were investigated. Cells expressing mu-opioid receptors targeted with single microinjection saporin conjugated agonist dermorphin; unconjugated dermorphin used as controls. dermorphin-saporin,...
Paradoxical opioid-induced pain has been demonstrated repeatedly in humans and animals. The mechanisms of such are unknown but may relate to activation descending facilitatory systems enhanced expression pronociceptive actions spinal dynorphin. Here, the possibility that these central changes might mediate increased excitability cord was tested. Tactile thermal hypersensitivity observed at 7, not 1, days after subcutaneous morphine pellet implantation; placebo pellets produced no effects....
Neuropathic pain states are accompanied by increased sensitivity to both noxious and non-noxious sensory stimuli, characterized as hyperalgesia allodynia, respectively. In animal models of neuropathic pain, the presence allodynia neuroplastic changes including spinal levels substance P, cholecystokinin (CCK), dynorphin. N-Methyl- d-aspartate (NMDA) receptors appear be involved in maintaining central which contributes pain. addition its opioid activities, dynorphin has been suggested act at...
Abstract Objective Identification of the neural mechanisms underlying medication overuse headache resulting from triptans. Methods Triptans were administered systemically to rats by repeated intermittent injections or continuous infusion over 6 days. Periorbital and hind paw sensory thresholds measured detect cutaneous allodynia. Immunofluorescent histochemistry was employed changes in peptidic neurotransmitter expression identified dural afferents. Enzyme‐linked immunoabsorbent assay used...
Experimental nerve injury results in exaggerated responses to tactile and thermal stimuli that resemble some aspects of human neuropathic pain. Neuronal hyperexcitability neurotransmitter release have been suggested promote such increased sensory stimuli. Enhanced activity Ca(2+) current is associated with neuronal blockade N- P-types, but not L-type, calcium channels found block experimental While T-type currents are believed excitability transmitter release, it unclear whether these may...
A puzzling observation is why peripheral nerve injury results in chronic pain some, but not all, patients. We explored potential mechanisms that may prevent the expression of pain. Sprague Dawley (SD) or Holtzman (HZ) rats showed no differences baseline sensory thresholds responses to inflammatory stimuli. However, spinal ligation (SNL)-induced tactile allodynia occurred approximately 85% SD and 50% HZ rats, respectively. No apparent were observed a survey dorsal root ganglion neuropathic...
Complete or partial spinal section at T8 has been shown to block tactile allodynia but not thermal hyperalgesia following L5/L6 nerve ligation (SNL), suggesting the supraspinal integration of in neuropathic pain. In present study, possibility mediation injury-associated pain through tonic activity descending nociceptive facilitation arising from rostroventromedial medulla (RVM) was investigated. Specifically, actions brainstem cholecystokinin and possible importance sustained afferent input...