A5017503792- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Cancer, Stress, Anesthesia, and Immune Response
- Pain Management and Opioid Use
- Ion channel regulation and function
- Neurotransmitter Receptor Influence on Behavior
- Migraine and Headache Studies
- Musculoskeletal pain and rehabilitation
- Botulinum Toxin and Related Neurological Disorders
- Ion Channels and Receptors
- Axon Guidance and Neuronal Signaling
- Pharmacological Effects of Natural Compounds
- Nerve injury and regeneration
- Chemical Synthesis and Analysis
- Sleep and Wakefulness Research
- Cancer Treatment and Pharmacology
- Forensic Toxicology and Drug Analysis
- Biochemical effects in animals
- Neuroscience of respiration and sleep
- Pain Management and Placebo Effect
- Adenosine and Purinergic Signaling
University of Arizona
2016-2025
National Institutes of Health
2020
University of Calgary
2020
University of Messina
2020
The University of Adelaide
2020
Scripps Research Institute
2020
Saint Louis University
2020
University of California, San Diego
2020
National Institute of Diabetes and Digestive and Kidney Diseases
2020
Johns Hopkins Medicine
2020
CB(2) cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with lack receptors in normal CNS. To date, there has been virtually no information regarding mechanism receptor-mediated inhibition responses. Here, we test hypothesis that stimulates release from keratinocytes endogenous opioid beta-endorphin,...
We designed AM1241, a selective CB 2 cannabinoid receptor agonist, and used it to test the hypothesis that activation would reverse sensory hypersensitivity observed in neuropathic pain states. AM1241 exhibits high affinity selectivity for receptors. It also potency vivo . dose-dependently reversed tactile thermal produced by ligation of L5 L6 spinal nerves rats. These effects were selectively antagonized but not 1 antagonist, suggesting they actions at was active blocking nerve...
The vanilloid receptor 1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel expressed by peripheral sensory neurons. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Here, we describe the vitro vivo pharmacology novel antagonist, AMG 9810, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide. 9810 competitive antagonist capsaicin activation (IC50 value for human TRPV1, 24.5 +/- 15.7 nM; rat 85.6 39.4...
Vanilloid receptor 1 (TRPV1), a membrane-associated cation channel, is activated by the pungent vanilloid from chili peppers, capsaicin, and ultra potent Euphorbia resinifera, resiniferatoxin (RTX), as well physical stimuli (heat protons) proposed endogenous ligands (anandamide, N-arachidonyldopamine, N-oleoyldopamine, products of lipoxygenase). Only limited information available in TRPV1 on residues that contribute to activation. Interestingly, rabbits have been suggested be insensitive...
Background Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, produced sustained in opioids, analgesia, or diminished measures This study tests hypothesis that regular aerobic leads reversal neuropathic pain by activating opioid-mediated modulatory systems. Methods After baseline measurements, L5 and L6 spinal nerves male Sprague-Dawley rats were...
Abstract Co-occurrence of chronic pain and clinically significant symptoms anxiety and/or depression is regularly noted in the literature. Yet, little known empirically about population prevalence co-occurring symptoms, nor whether people with constitute a distinct subpopulation within US adults living or (A/D). To address this gap, study analyzes data from 2019 National Health Interview Survey, representative annual survey self-reported health status treatment use United States (n =...
Cannabinoid receptor agonists diminish responses to painful stimuli. Extensive evidence implicates the CB(1) in production of antinociception. However, capacity CB(2) receptors, which are located outside central nervous system (CNS), produce antinociception is not known. Using AM1241, a receptor-selective agonist, we demonstrate that receptors thermal Injection AM1241 hindpaw produced stimulus applied same paw. an equivalent dose into paw contralateral side testing did not. The...
Differential expression of ion channels contributes functional diversity to sensory neuron signaling. We find nerve injury induced by the Chung model neuropathic pain leads striking reductions in voltage-gated K + (Kv) channel subunit dorsal root ganglia (DRG) neurons, suggesting a potential molecular mechanism for hyperexcitability injured nerves. Moreover, specific classes DRG neurons express distinct Kv combinations. Importantly, Kv1.4 is sole Kv1 α expressed smaller diameter that...
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....
This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) [D-Ala2] deltorphin II as well to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a mu agonist, in mice. Intracerebroventricular administration DPDPE, [D-Ala2]deltorphin DAMGO each produced an effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted shown by 4.8-fold rightward shift dose-response curve. In...
Background Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models. Nonselective cannabinoid also produce central nervous system (CNS) side effects. Agonists selective for CB2 receptors, which are not found the CNS, do CNS effects typical of nonselective but acute nociception. The authors used receptor-selective agonist AM1241 to test hypothesis that activation peripheral receptors inhibits hyperalgesia. Methods Rats were injected hind paw with carrageenan or...
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...
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...
Opioid-induced hyperalgesia is characterized by hypersensitivity to innocuous or noxious stimuli during sustained opiate administration. Microinjection of lidocaine into the rostral ventromedial medulla (RVM), dorsolateral funiculus (DLF) lesion, abolishes opioid-induced hyperalgesia, suggesting importance descending pain facilitation mechanisms. Here, we investigate possibility that cholecystokinin (CCK), a pronociceptive peptide, may drive such from RVM continuous opioid In opioid-naive...