A5058964609- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Musculoskeletal pain and rehabilitation
- Pain Management and Opioid Use
- Pain Management and Placebo Effect
- Stress Responses and Cortisol
- Osteoarthritis Treatment and Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Botulinum Toxin and Related Neurological Disorders
- Pediatric Pain Management Techniques
- Pharmacological Receptor Mechanisms and Effects
- Bone health and treatments
- Cannabis and Cannabinoid Research
- Ion Channels and Receptors
- Pharmacological Effects and Assays
- Migraine and Headache Studies
- Nerve injury and regeneration
- Bone Metabolism and Diseases
- Healthcare and Venom Research
- MicroRNA in disease regulation
- Pelvic floor disorders treatments
- Neurobiology and Insect Physiology Research
University of New England
2015-2025
University of Maine
2019-2022
New England College
2015-2021
Shepherd Center
2003-2021
UConn Health
2019
University of New England
2019
University of Arizona
2005-2015
Christie's
2011-2015
Fundación Juan March
2015
Center for Excellence in Education
2013
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...
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...
Neuropathic pain is often "spontaneous" or "stimulus-independent." Such may result from spontaneous discharge in primary afferent nociceptors injured peripheral nerves. However, whether axotomized give rise to unclear. The rostral anterior cingulate cortex (rACC) mediates the negative affective component of inflammatory pain. Whether rACC integrates aversive chronic arising nerve injury not known. Here, we used principle reinforcement show that axotomy produces an state reflecting driven...
Abstract Objective To develop and validate a model of cutaneous allodynia triggered by dural inflammation for pain associated with headaches. explore neural mechanisms underlying cephalic extracephalic allodynia. Methods Inflammatory mediators (IM) were applied to the dura unanesthetized rats via previously implanted cannulas, sensory thresholds face hind‐paws characterized. Results IM elicited robust facial hind‐paw allodynia, which peaked within 3 hours. These effects reminiscent seen in...
Opiates are among the most important drugs for treatment of moderate to severe pain and prolonged opiate administration is often required treat chronic states. We investigated neurobiological actions sustained revealing paradoxical pronociceptive adaptations associated with NK-1 receptor function. Sustained morphine delivered over 6 days elicited hyperalgesia in rats mice during period delivery. increased substance P (SP) expression spinal dorsal horn. also enhanced capsaicin-evoked SP...
Osteoarthritis (OA) is a chronic condition characterized by pain during joint movement. Additionally, patients with advanced disease experience at rest (ie, ongoing pain) that generally resistant to nonsteroidal antiinflammatory drugs. Injection of monosodium iodoacetate (MIA) into the intraarticular space rodent knee well-established model OA elicits weight-bearing asymmetry and referred tactile thermal hypersensitivity. Whether present in this unknown. possible relationship MIA dose not...
Metastatic bone cancer causes severe pain that is primarily treated with opioids. A model of in which the progression and destruction tightly controlled was used to evaluate effects sustained morphine treatment. In cancer-treated mice, enhanced, rather than diminished, spontaneous, evoked pain; these were dose-dependent naloxone-sensitive. SP CGRP positive DRG cells did not differ between sarcoma or control but increased following both groups. Morphine ATF-3 expression only mice. alter tumor...
Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief reward in nerve-injured rats. This approach was used evaluate the temporal mechanistic features of inflammation-induced ongoing pain.Intraplantar Complete Freund's Adjuvant (CFA) produced thermal hyperalgesia guarding behavior reliably observed within 24 hrs maintained, albeit diminished, 4 days post-administration. Spinal clonidine robust...
Summary TRPV1 fibers and spinal NK-1 expressing ascending projections mediate spontaneous pain evoked hypersensitivity. Large-diameter tactile A predominant complaint in patients with neuropathic is pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask allowing for mechanistic investigations. Here, pathways might contribute components of an experimental model were explored. Desensitization TRPV1-positive systemic resiniferatoxin...
Abstract Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity produced conditioned place preference (CPP) dopamine (DA) release the nucleus accumbens (NAc) selectively SNL Spinal also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to...
Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa receptors (KORs), a key mediator of stress responses. The aim this study was to use injury-free rat model functional cephalic pain with features and medication overuse headache (MOH) test possible preventive benefit KOR blockade on stress-induced pain. Methods Following sumatriptan priming MOH, rats were hyper-responsive environmental stress, demonstrating...
Most commonly originating from breast malignancies, metastatic bone cancer causes destruction and severe pain. Although novel chemotherapeutic agents have increased life expectancy, patients are experiencing higher incidences of fracture, pain, drug-induced side effects; furthermore, recent findings suggest that severely undertreated for their Strong analgesics, namely opiates, first-line therapy in alleviating cancer-related pain despite the effects, including enhanced with sustained...
The delivery of peptide drugs to the brain is challenging, principally due blood barrier and low metabolic stability peptides. Exclusive with no peripheral exposure has hitherto not been demonstrated quantification data. Here we show that polymer nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able transport LENK exclusively via intranasal route, nanoparticle localisation observed within parenchyma. Animals dosed (NM0127) showed a strong anti-nociceptive response in...
Unresolved inflammation is a significant predictor for developing chronic pain, and targeting the mechanisms underlying offers opportunities therapeutic intervention. During inflammation, matrix metalloproteinase (MMP) activity contributes to tissue remodeling inflammatory signaling, regulated by inhibitors of metalloproteinases (TIMPs). TIMP-1 -2 have known roles in but only context MMP inhibition. However, also has receptor-mediated cell signaling functions that are not well understood....