A5058106389- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Hemoglobinopathies and Related Disorders
- Cannabis and Cannabinoid Research
- Sleep and Wakefulness Research
- Ion channel regulation and function
- Dermatology and Skin Diseases
- Biochemical effects in animals
- Pain Management and Placebo Effect
- Allergic Rhinitis and Sensitization
- Anesthesia and Pain Management
- Neuroscience and Neuropharmacology Research
- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Asthma and respiratory diseases
- Neurological and metabolic disorders
- Nerve injury and regeneration
- Sphingolipid Metabolism and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Neurogenesis and neuroplasticity mechanisms
- Diet and metabolism studies
- Cancer Treatment and Pharmacology
- Pharmacological Receptor Mechanisms and Effects
- Neurotransmitter Receptor Influence on Behavior
- Pediatric Pain Management Techniques
University of Minnesota
2012-2024
University of Minnesota System
2018-2023
Brigham and Women's Hospital
2018
Office of Basic Energy Sciences
2007-2012
General Department of Preventive Medicine
2001-2002
University of Leeds
1998-1999
Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch blocked using antihistamines, others cannot these constitute important clinical problem. Little information available on the mechanisms underlying that produced by nonhistaminergic mechanisms. We examined responses spinothalamic tract neurons to histaminergic and, for first time, stimuli. Fifty-seven primate (STT) were identified antidromic activation...
In previous studies, we have shown that loss of spinal neurons possess the substance P receptor (SPR) attenuated pain and hyperalgesia produced by capsaicin, inflammation, nerve injury. To determine role SPR-expressing in modulating hyperalgesia, responses superficial deep lumbar dorsal horn evoked mechanical heat stimuli capsaicin were made after ablation using selective cytotoxin conjugate P-saporin (SP-SAP). Morphological analysis electrophysiological recordings intrathecal infusion...
The increasing use of transgenic mice for the study pain mechanisms necessitates comprehensive understanding murine somatosensory system. Using an in vivo mouse preparation, we studied response properties tibial nerve afferent fibers innervating glabrous skin. Recordings were obtained from 225 identified by mechanical stimulation Of these, 106 classed as Aβ mechanoreceptors, 51 Aδ fibers, and 68 C fibers. mechanoreceptors had a mean conduction velocity 22.2 ± 0.7 (SE) m/s (13.8–40.0 m/s)...
Itch of peripheral origin requires information transfer from the spinal cord to brain for perception. Here, primate spinothalamic tract (STT) neurons lumbar were functionally characterized by in vivo electrophysiology determine role these cells transmission pruriceptive information. One hundred eleven STT identified antidromic stimulation and then recorded while histamine cowhage (a nonhistaminergic pruritogen) sequentially applied cutaneous receptive field each cell. Twenty percent...
Painful peripheral neuropathy is a dose-limiting complication of chemotherapy. Cisplatin produces cumulative toxic effect on nerves, and 30–40% cancer patients receiving this agent experience pain. By modeling cisplatin-induced hyperalgesia in mice with daily injections cisplatin (1 mg/kg, i.p.) for 7 d, we investigated the anti-hyperalgesic effects anandamide (AEA) cyclohexylcarbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597), an inhibitor AEA hydrolysis. Cisplatin-induced mechanical...
Tumors in bone are associated with pain humans. Data generated a murine model of cancer suggest that disturbance local endocannabinoid signaling contributes to the pain. When tumors formed after injection osteolytic fibrosarcoma cells into calcaneus mice, cutaneous mechanical hyperalgesia was decrease level anandamide (AEA) plantar paw skin ipsilateral tumors. The AEA occurred conjunction increased degradation by fatty acid amide hydrolase (FAAH). Intraplantar reduced hyperalgesia, and...
Abstract Painful peripheral neuropathy is a dose-limiting side effect of cisplatin treatment. Using murine model cisplatin-induced hyperalgesia, we determined whether PPARγ synthetic agonist, pioglitazone, attenuated the development neuropathic pain and identified underlying mechanisms. Cisplatin produced mechanical cold hyperalgesia decreased electrical thresholds Aδ C fibers, which were by coadministration pioglitazone (10 mg/kg, intraperitoneally [i.p.]) with cisplatin. Antihyperalgesic...
Pain associated with bone cancer remains poorly managed, and chemotherapeutic drugs used to treat usually increase pain. The discovery of dual-acting that reduce produce analgesia is an optimal approach. mechanisms underlying pain involve interactions between cells nociceptive neurons. We demonstrated fibrosarcoma express high levels autotaxin (ATX), the enzyme synthetizing lysophosphatidic acid (LPA). Lysophosphatidic increased proliferation in vitro. also a pain-signaling molecule, which...
Vaso-occlusive pain episodes (VOE) cause severe in patients with sickle cell disease (SCD). events promote ischemia/reperfusion pathobiology that activates complement. We hypothesized complement activation is linked to VOE. used cold induce VOE the Townes homozygous for hemoglobin S (HbSS) mouse model and inhibitors determine whether anaphylatoxin C5a mediates a dorsal skinfold chamber measure microvascular stasis (vaso-occlusion) von Frey filaments applied plantar surface of hind paw assess...
The role of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) was studied using extracellular single-unit recording combined with microiontophoresis. In rats, on- and off-type neurons were identified noxious heat or mechanical stimuli applied to tail. Responses evoked by iontophoretic application N-methyl-d-aspartate (NMDA) determined before after intraplantar injection capsaicin substance P. off cells, produced an extended pause ongoing activity but did not alter...
The rostral ventromedial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests substance P activation neurokinin-1 (NK-1) receptors in are involved facilitation nociception. We showed previously injection NK-1 receptor antagonists into attenuated mechanical heat hyperalgesia produced by...
The effects of a mild freeze injury to the skin on responses nociceptive dorsal horn neurons cold and heat stimuli were examined in anesthetized rats. Electrophysiological recordings obtained from 72 spinal located superficial deep horn. All had receptive fields (RFs) glabrous hindpaw, functionally divided into wide dynamic range (WDR) high-threshold (HT) neurons. Forty-four (61%) classified as WDR responded both innocuous noxious mechanical (mean threshold 12.8 ± 1.6 mN). Twenty-eight (39%)...
The in vitro hemisected spinal cord from young rat was used to investigate the mechanism of serotoninergic modulation primary afferent‐mediated synaptic transmission dorsal horn through activation 5‐HT 3 receptor. Dorsal root‐evoked excitatory post‐synaptic potentials (DR‐EPSPs) were recorded intracellularly neurones. Extracellular recordings population afferent depolarization (PAD) and rootevoked root reflex (DR‐DRR) made segmental roots. 5‐Hydroxytryptamine (5‐HT) selective receptor...
Selective ablation of spinal neurons possessing substance P receptors (NK-1 receptors) using the selective cytotoxin conjugate P-saporin (SP-SAP) decreases hyperalgesia and central sensitization. The mechanisms by which NK-1 expressing modulate excitability other dorsal horn are unclear. Because majority project rostrally, it is possible that they part a spinal-supraspinal circuitry contributes to descending modulation nociceptive neurons. We therefore determined whether possess receptor...
Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to chronic pain hyperalgesia accompanying this condition. This study focused on role endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in process cancer Electrophysiological response properties, including ongoing activity responses evoked by heat stimuli, were recorded vivo...
The rostral ventromedial medulla (RVM) is an area of the brainstem involved in descending modulation nociception at level spinal cord. Although RVM inhibition or facilitation nociception, underlying mechanisms are not understood. Here we examined role neuropeptide substance P and neurokinin-1 (NK-1) receptors located on withdrawal responses evoked by mechanical heat stimuli applied to rat hindpaw under normal conditions during hyperalgesia produced capsaicin. threshold was obtained using von...
Neurons in the rostral ventromedial medulla (RVM) project to spinal cord and are involved descending modulation of pain. Several studies have shown that activation neurokinin-1 (NK-1) receptors RVM produces hyperalgesia, although underlying mechanisms not clear. In parallel studies, we compared behavioral measures hyperalgesia electrophysiological responses nociceptive dorsal horn neurons produced by NK-1 RVM. Injection selective receptor agonist Sar9,Met(O
Sickle cell disease (SCD) is the most common inherited disease. Pain a key morbidity of SCD and opioids are main treatment but their side effects emphasize need for new analgesic approaches. Humanized transgenic mouse models have been instructive in understanding pathobiology mechanisms pain. Homozygous (HbSS) Berkley mice express >99% human sickle hemoglobin several features clinical including hyperalgesia. Previously, we reported that endocannabinoid 2-arachidonoylglycerol (2-AG)...