Office: 210-567-3381
E-mail: Hargreaves@uthscsa.edu
My primary research interests are in the pharmacology of pain and inflammation. A major focus is on pharmacological regulation of unmyelinated "C" fiber nociceptors, as well as their plasticity in response to inflammation or nerve injury. Investigations are in progress evaluating the effects of cannabinoids, opioids, adrenergics, NPY, sex steroids and other drugs on regulating the activity of these fibers. In addition, we are interested in identifying major classes of inflammatory mediators and associated receptor/signal transduction systems which mediate activation, sensitization and phenotypic plasticity of these primary afferent fibers in response to tissue inflammation. Responses are measured using isolated superfused tissue, primary trigeminal cultures, microdialysis probes implanted in situ, RIA, EIA, real time PCR, Affymetrex analyses, IHC, ISH, confocal microscopy, behavior, etc.
Selected Publications
Akopian A, Ruparel N, Jeske N, Hargreaves KM. TRPA1 desensitization in sensory neurons is agonist-dependent and regulated by TRPV1-directed internalization. J Physiol (Lond.) (in press) 2007.
Ruparel N, Patwardhan A, Akopian A, Hargreaves KM. Homologous and heterologous desensitization of capsaicin and mustard oil responses utilize different cellular pathways in nociceptors. Pain (in press) 2007.
Berg K, Patwardhan A, Sanchez T, Silva Y, Hargreaves KM, Clarke W. Rapid regulation of Mu opiod receptor signaling in primary sensory neurons. J Pharmacol Expt Therap 321:839, 2007.
Gibbs J, Diogenes A, Hargreaves KM. Neuropeptide Y modulates effects of bradykinin and prostaglandin E2 on trigeminal nociceptors via activation of the Y1 and Y2 receptors. Br J Pharmacol 150:72-9, 2007.
Berg K, Zardeneta G, Hargreaves KM, Clarke W, Milam S. Integrins regulate opioid receptor signaling in trigeminal ganglion neurons. Neuroscience 144:889-95, 2007.
Diogenes A, Akopian A, Hargreaves KM. NGF Upregulates TRPA1. J Dent Res 86:550-5, 2007.
Patwardhan A, Jeske N, Price T, Gamper N, Akopian A, Hargreaves KM. The cannabinoid WIN-55212-2 inhibits TRPV1 responses and evokes peripheral antihyperalgesia/antinociception via activation of the calcineurin pathway. Proc Natl Acad Sci USA 103:11393-8, 2006.
Jeske N, Patwardhan A, Gamper N, Price T, Akopian A, Hargreaves KM. Cannabinoid Win 55,212-2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem 281(43):32879-90, 2006.
Diogenes A, Patwardhan A, Jeske N, Ruparel N, Goffin V, Akopian A, Hargreaves KM. Prolactin Modulates TRPV1 in Female Rat Trigeminal Sensory Neurons. J. Neuroscience 26:8126-36, 2006.
Patwardhan A, Diogenes A, Berg K, Fehrenbacher J, Clarke W, Akopian A, Hargreaves KM. PAR-2 agonists activate trigeminal nociceptors and induce functional competence in the Delta opioid receptor. Pain 125:114-24, 2006.
Price T, Hargreaves KM and Cevero F. Protein expression and mRNA cellular distribution of the NKCC1 co-transporter in the dorsal root and trigeminal ganglia of the rat. Brain Res 1112:146-58, 2006.
Price T, Flores C, Hargreaves KM. The RNA binding and transport proteins staufen and fragile X mental retardation protein are expressed by rat primary afferent neurons and localize to preipheral and central axons. Neuroscience 141:2107-16, 2006.
Gibbs J, Flores C, and Hargreaves KM. Attenuation of capsaicin-evoked mechanical allodynia by peripheral neuropeptide Y Y1 receptors. Pain 124:167-74, 2006.
Wadachi R and Hargreaves KM. Trigeminal Nociceptors Express TLR-4 and CD14. A Mechanism for Pain due to Infection. J Dent Res 85:49-52, 2006.
Bowles W, Hargreaves KM. Chronic Nerve Growth Factor Administration Increases the Peripheral Exocytotic Activity of Capsaicin-Sensitive Cutaneous Neurons. Neurosci Lett 403:305-8, 2006.
Patwardhan A, Berg K, Akopian A, Jeske N, Gamper N, Clarke W, and Hargreaves KM. Bradykinin induced functional competence and trafficking of the delta opioid receptor in trigeminal nociceptors. J Neurosci 25:8825-32, 2005.
Price TJ, Jeske N, Flores CM, Hargreaves KM. Pharmacological interactions between calcium/calmodulin-dependent kinase II α and TRPV1 receptors in rat trigeminal sensory neurons. Neurosci Lett 389:94-8, 2005.
Price TJ, Patwardhan AM, Flores CM, Hargreaves KM. A role for the anandamide membrane transporter in TRPV1 mediated neurosecretion from trigeminal nociceptors. Neuropharmacol. 49:25-39, 2005.
Price TJ, Louria MD, Candelario-Soto D, Dussor GO, Jeske NA, Patwardhan AM, Diogenes A, Trott AA, Hargreaves KM, Flores CM. Treatment of trigeminal ganglion neurons in vitro with NGF, GDNF, and BDNF: effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion. BMC Neurosci. 2005 Jan 24;6(1):4.
Gibbs J, Flores C, Hargreaves KM. NPY inhibits capsaicin-sensitive nociceptors via a Y1 receptor mediated mechanism. Neuroscience 125:703-9, 2004.
Price T, Patwardhan A, Akopian A, Hargreaves K, Flores, C. Cannabinoid receptor independent actions of the aminoalkylindole cannabinoid Win 55212-2 on trigeminal sensory neurons. Br J Pharmacol 142:257-66, 2004.
Price T, Patwardhan A, Akopian A, Hargreaves K, Flores C. Modulation of trigeminal sensory neurons by the dual cannabinoid-vanilloid agonists anandamide (AEA), N-arachidonyl-dopamine (NADA) and arachdonyl-2-chloroethylamide (ACEA). Br J Pharmacol 141:1118-30, 2004.
Dussor G, Helesic G, Hargreaves K, Flores C. Cholinergic modulation of nociceptive responses in vivo and neuropeptide release in vitro at the level of the primary sensory neuron. Pain 107:22-31, 2004.
Dussor GO. Leong AS. Gracia NB. Kilo S. Price TJ. Hargreaves KM. Flores CM. Potentiation of evoked calcitonin gene-related peptide release from oral mucosa: a potential basis for the pro-inflammatory effects of nicotine. European Journal of Neuroscience. 18(9):2515-26, 2003.
Bowles WR, Flores CM, Jackson DL, Hargreaves KM. α-Adrenoceptor regulation of CGRP release from capsaicin-sensitive neurons. J Dent Res 82:308-311, 2003.
Hargreaves KM, Bowles WR, Jackson DL. Intrinsic regulation of iCGRP release from dental pulp sympathetic fibers. J Dent Res 82:398, 2003.
Price T, Helesic G, Parghi D, Hargreaves KM, Flores C. The neuronal distribution of cannabinoid receptor type one in the trigeminal ganglion of the rat. Neuroscience 120:155-62, 2003.
Dussor G, Leong A, Gracia N, Kilo S, Price T, Hargreaves, KM, Flores C. A cellular and molecular basis for the pro-inflammatory effects of nicotine: potentiation of capsaicin-evoked CGRP release from oral mucosal. Eur J Neurosci 18:2515-30, 2003.
