A5042389999- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Anesthesia and Pain Management
- Neuroscience and Neuropharmacology Research
- Pain Management and Opioid Use
- Botulinum Toxin and Related Neurological Disorders
- Pharmacological Receptor Mechanisms and Effects
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Pain Management and Placebo Effect
- Spine and Intervertebral Disc Pathology
- Cancer Treatment and Pharmacology
- Veterinary Pharmacology and Anesthesia
- Musculoskeletal pain and rehabilitation
- Pediatric Pain Management Techniques
- Epilepsy research and treatment
- Anesthesia and Sedative Agents
- Anesthesia and Neurotoxicity Research
- Inflammatory mediators and NSAID effects
- Pharmacological Effects of Natural Compounds
- Neurotransmitter Receptor Influence on Behavior
- Nicotinic Acetylcholine Receptors Study
- Neuroscience of respiration and sleep
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
University of California, San Diego
2016-2025
Hillcrest Hospital
2021
Asana Biosciences (United States)
2020
International Neuromodulation Society
2019
Therapeutics Clinical Research
2018
Universidade Federal de Mato Grosso do Sul
2016
Mayo Clinic in Arizona
1980-2015
University Medical Center Utrecht
2012-2014
University College London
1978-2013
Oregon Health & Science University
2012-2013
Narcotic analgetics administered directly into the spinal subarachnoid space of rat via a chronically inserted catheter produce potent analgesia that can be antagonized by naloxone. The narcotics, acting only at level, changed cord function to block not reflexes but also operant response painful stimuli.
Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in the periphery is commonly accepted as primary mechanism which these agents produce a selective attenuation pain (analgesia). NSAIDs are now shown to exert direct spinal action blocking excessive sensitivity (hyperalgesia) induced activation glutamate and substance P receptors. These findings demonstrate that analgesic effects can be dissociated from their actions. Spinal prostanoids thus critical for augmented...
Intrathecal administration of glycine (strychnine) or GABA (bicuculline) but not opioid (naloxone), adrenergic (phentolamine) serotonin (methysergide) receptor antagonists resulted in a dose-dependent organized agitation response to light tactile stimulation. This effect was maximally evoked by oscillating continuous stimulation applied dermatome corresponding the levels spinal cord acted upon intrathecal antagonist. Similar results were observed chloralose-urethane anesthetized rats which...
Peripheral nerve injury can lead to a persistent neuropathic pain state in which innocuous tactile stimulation elicits behavior (tactile allodynia). Spinal administration of the anticonvulsant gabapentin suppresses allodynia by an unknown mechanism. In vitro studies indicate that binds alpha(2)delta-1 (hereafter referred as alpha(2)delta) subunit voltage-gated calcium channels. We hypothesized may result altered alpha(2)delta expression spinal cord and dorsal root ganglia (DRGs) this change...
The effects of intrathecally administered opiates (morphine sulfate and meperidine), alpha-adrenergic agonists (clonidine ST-91) baclofen were examined on the shock titration threshold macaque monkeys chronically prepared with intrathecal (I) or epidural (E) catheters. Spinal produced a long-lasting analgesia which was antagonized by naloxone. order potency I morphine greater than meperidine E morphine. Clonidine ST-91, also dose-dependent, elevation in threshold, phentolamine, but not...
Intrathecal administration of norepinephrine (NE) and alpha adrenergic agonists in rats with chronic spinal catheters produced a significant elevation the nociceptive threshold as measured by hot plate tail flick. The intrathecal NE effect was dose-dependent antagonized competitive fashion pretreatment phentolamine (alpha antagonist) but not propranolol (beta antagonist). isoproterenol agonist) did alter threshold. Effective doses produce demonstrable motor effects. Doses 20 times greater...
To assess the possible role of spinal nitric oxide (NO) synthesis in nociceptive processing, we examined effect intrathecal (i.t.) injection arginine analogs that act as alternate substrates for NO synthase and thus inhibit production. NG-nitro-L-arginine ester (r-NAME) NG-monomethyl-L-arginine (L-NMMA) produced a dose-dependent, stereospecific inhibition second phase (10-60 min; ED50, 135 246 nmol) formalin test with minimal on first (0-9 ED50 > 1.1 mumol). The inhibitory action L-NAME was...
The intrathecal administration of mu (morphine) and delta (D-Ala2-D-Leu5-enkephalin) but not kappa agonists (ethylketocyclazocine, bremazocine U50488H) or partial (nalbuphine buprenorphine) produced a dose-dependent inhibition all cutaneous thermal (hot plate tail-flick) responses in the rat. In contrast, on visceral chemical tests (writhing), exerted powerful suppression response. Whereas ED50 morphine did differ from that observed test, agents with significant activity (metkephamid...
Abstract We examined the effect of p38 mitogen‐activated protein kinase (MAPK) inhibitors in models nociception and correlated this with localization expression levels MAPK spinal cord. There was a rapid increase phosphorylated cord following intrathecal administration substance P or intradermal injection formalin. Immuncytochemisty revealed that MAPK‐immunoreactive cells were predominantly present laminae I–IV dorsal horn. Double‐staining markers for neurons, microglia, astrocytes...
1. The present experiments examine the physiology and pharmacology of release substance P‐like immunoreactivity (SP‐l.i.), from spinal cord in halothane‐anaesthetized, artificially ventilated cat. 2. Resting SP‐l.i. was 36 +/‐ 4 fmol/30 min (mean S.E.; n = 106). Bilateral stimulation sciatic nerves at intensities which evoked activity fibres conducting A beta conduction velocities (greater than 40 m/s), resulted no change blood pressure, pupil diameter or Stimulation activate less 2 m/s...
A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal chemical pain thresholds rat but no apparent change responses to noxious mechanical stimuli.
Neuropathic pain remains a significant clinical problem. Current understanding implicates the spinal cord dorsal horn N-methyl-d-aspartate (NMDA) receptor apparatus in its pathogenesis. Previous reports have described NMDA antagonist reduction of nerve injury-induced thermal hyperalgesia and formalin injection-related electrical activity. We examined panel spinally administered antagonists two models: allodynia evoked by tight ligation fifth sixth lumbar nerves (a model chronic injury pain),...
Current thinking emphasizes that protracted small afferent input can evoke mechanisms mediate a significant potentiation of spinal nociceptive processing and this facilitory component has unique pharmacology. To investigate the behavioral parallels facilitation, we evaluated effects pre- post-treatment intrathecal morphine (mu agonist) MK801 (N-methyl-D-aspartate [NMDA] antagonist) on formalin test. Intraplantar resulted in biphasic appearance flinching behavior (phase 1 = 0-5 min; phase 2...