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Neuroscience

Steven McGaraughty

McGaraughty-Steve

Lecturer in Neuroscience

Specialization

Pain Modulation
Drug Discovery
Neuro-Immune Interactions
Neuro-Electrophysiology

Research Interests

I have conducted research to support the development of novel pharmacological treatments for Chronic Pain, and other Neuroscience disorders as well as for Fibrotic and Skin diseases. My teams conducted behavioral, electrophysiological, fMRI imaging, histological, and clinical testing to evaluate novel pharmacology. These teams were typically tasked with understanding the mechanistic undertones and behavioral effects of the pharmacology that we were developing. My general research interests lie in how pain is modulated by many other neural systems, such as those associated with anxiety, attention, and arousal. In a similar vein, I have delved into the physiology behind how acupuncture and diffuse noxious inhibitory controls change the “pain signal”. I also have an interest in how the nervous system interacts with other non-nervous systems (e.g., the immune system) to affect a multitude of diseases such as Eczema and pathological itch.

Education

B.Sc. - Concordia University, Montreal, Quebec
Ph.D. and M.A. - University of Waterloo, Waterloo, Ontario
Post-Doctoral - McGill University, Montrea,l Quebec
Post-Doctoral - Oregon Health and Sciences University, Portland, Oregon

Courses Taught

NEUR 372  Pharmacology: Drug, Brain, Behavior

Selected Articles

Leys L., Lippert S., Wetter J., Salte K., Su, Z., Namovic M., Edelmayer R.M., Honore P., and McGaraughty S. Kinetic characterization of IL-23 minicircle model of skin inflammation in mice. The Journal of Dermatology, 46, 482-497 (2019).

McGaraughty S., Chu, K.L., and Xu, J. Characterization and Pharmacological Modulation of Noci-Responsive Deep Dorsal Horn Neurons Across Diverse Rat Models of Pathological Pain. Journal of Neurophysiology, 120: 1893-1905 (2018).

Brederson J-D, Chu K.L, Xu J., Mikusa J., Nikkel A.L, Markosyan S, Edelmeyer R, Bitner R.S., and McGaraughty S. Characterization and Comparison of Rat Monosodium Iodoacetate and Medial Meniscal Tear Models of Osteoarthritic Pain. Journal of Orthopaedic Research, 36: 2109-2117 (2018).

McGaraughty S., Davis-Taber, R.A., Zhu, C.Z., Cole, T.B., Nikkel, A.L., Chhaya, M., Doyle, K.J., Olson, L.M., Preston, G.M., Grinnell, C.M., Salte, K.M., Giamis, A.M., Luo, Y., Sun, V., Goodearl, A.D., Gopalakrishnan, M., and Lacy, S.E. Targeting Anti-TGF-B Therapy to Fibrotic Kidney with a Dual-Specificity Antibody Approach. Journal of American Society of Nephrology, 28: 3616-3626 (2017).

McGaraughty S, Chu, KL, Xu, J, Leys L, Radek R, Dart M, Kym PR, and Brederson JD. TRPV3 modulates nociceptive signaling through peripheral and supraspinal sites in neuropathic rats. Journal of Neurophysiology, 118: 904-916 (2017).

Su, Z., Widomski, D., Ma, J., Namovic, M., Nikkel A., Leys L., Olson L., Salte K., Donnelly-Roberts D., Esbenshade T., and McGaraughty S. Longitudinal changes in mGFR, renal fibrosis and biomarkers in a rat model of type 2 diabetic nephropathy. American Journal of Nephrology, 44: 339-353 (2016).

Chu KL., Xu J., Frost J., Li, L., Gomez E., Dart MJ., Jarvis MF., Meyer MD., and McGaraughty S. A-1262543, a selective alpha2B adrenoceptor agonist, and duloxetine modulate nociceptive neurons in the medial prefrontal cortex, but not spinal cord in neuropathic rats. European Journal of Pain, 19: 649-660 (2015).

Swensen AM., Niforatos W., Lee L., Jarvis MF., and McGaraughty S. Characterization of the triazine, T4, a representative from a novel series of CaV2 inhibitors with strong state-dependence, poor use-dependence, and distinctively fast kinetics, European Journal of Pharmacology, 745:234-242 (2014).

Xu J, Chu KL, Zhu CZ, Niforatos W, Swensen A, Searle X, Lee L, Jarvis MF, and McGaraughty S. A mixed Ca2+ channel blocker, A-1264087, utilizes peripheral and spinal mechanisms to inhibit spinal nociceptive transmission in a rat model of neuropathic pain. Journal of Neurophysiology, 111: 394-404 (2014).

Leys L., Chu KL., Xu J., Pai M., Yang S., Robb HM, Jarvis MF, Radek RJ., and McGaraughty, S. Disturbances in slow wave sleep are induced by models of bilateral inflammation, neuropathic, and post-operative, but not osteoarthritic pain in rats. Pain, 154: 1092-1102 (2013).

McGaraughty S., Chu K.L., Cowart M.D., and Brioni, J.D. Antagonism of supraspinal histamine H3 receptors modulates spinal neuronal activity in neuropathic rats. Journal of Pharmacology and Experimental Therapeutics, 343:13-20 (2012).

Swensen A.M., Niforatos W., Vortherms T.A., Perner R.J., Li T., Schrimpf M.R., Scott V.E., Lee L., Jarvis M.F., and McGaraughty S. An automated electrophysiological assay for differentiating CaV2.2 calcium channel inhibitors based on state-dependence and kinetics. Assay and Drug Development Technologies, 10:542-550 (2012).

Xu J., Chu, K.L., Brederson, J-D., Jarvis M.F., and McGaraughty S. Spontaneous firing and evoked responses of spinal nociceptive neurons are attenuated by blockade of P2X3/P2X2/3 receptors in inflamed rats. Neuroscience Research, 90:1597-1606 (2012).

Brederson J-D., Chu K.L., Reilly R., Brown B.S., Kym P.R., Jarvis M.F., and McGaraughty S. TRPV1 antagonist, A-889425, inhibits mechanotransmission in a subclass of rat primary afferent neurons following peripheral inflammation. Synapse, 66:187-195 (2012).

Rowbotham M., Nothaft W., Duan W.R., Faltynek C., McGaraughty S., Chu K., Svensson P. Oral and peripheral thermosensory profile of selective TRPV1 inhibition by ABT-102 in healthy volunteers. Pain, 152:1192-1200 (2011).

Chu K.L., Chandran P., Joshi S.K., Jarvis M.F., Kym P.R., and McGaraughty S. TRPV1-related modulation of spinal neuronal activity and behavior in a rat model of osteoarthritic pain. Brain Research, 1369:158-166 (2011).

McGaraughty S, Chu K.L., Perner R.J., DiDomenico S., Kort M.E., and Kym P.R. TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Molecular Pain, 6:14 (2010).

McGaraughty S., Segreti J.A., Fryer R.M., Brown B.S., Faltynek C.R., and Kym P.R. Antagonism of TRPV1 receptors indirectly modulates activity of thermoregulatory neurons in the medial preoptic area of rats. Brain Research, 1268, 58-67 (2009).

McGaraughty S., Chu K.L., Dart M.J., Yao B.B., and Meyer M.M. A CB2 receptor agonist, A-836339, modulates WDR neuronal activity in neuropathic rats: contributions of spinal and peripheral CB2 receptors. Neuroscience, 158, 1652-1661 (2009).

McGaraughty S., Chu K.L., Brown B.S., Zhu C.Z., Zhong C., Joshi S.K., Honore P., Faltynek C.R., and Jarvis, M.F. Contributions of central and peripheral TRPV1 receptors to mechanically evoked and spontaneous firing of spinal neurons in inflamed rats. Journal of Neurophysiology, 100: 3158-3166 (2008).

McGaraughty S., Chu K.L., Scani, M.J.C., Kor, M.E., Faltynek C.R., and Jarvis M.F. A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats. Journal of Pharmacology and Experimental Therapeutics, 324:1204-1211 (2008).

McGaraughty S., Chu K.L., Namovic M.T., Donnelly-Roberts D.L., Harris R.R., Zhang X-F., Shieh C-C., Wismer C.T., Zhu C.Z., Gauvin D.M., Fabiyi A.C., Honore P., Gregg R.J., Kort M.E., Nelson D.W., Carroll W.A., Marsh K., Faltynek C.R., and Jarvis M.F. P2X7-related modulation of pathological nociception in rats. Neuroscience, 146, 1817-1828 (2007).

McGaraughty S, and Jarvis M.F. Purines and neuropathic pain. Drug Development Research, Review, 67, 376-388 (2006).

Fox G.B., McGaraughty S., Luo Y. Pharmacological and functional magnetic resonance imaging techniques in CNS drug discovery, Expert Opinion on Drug Discovery, Review, 1, 211-224 (2006).

McGaraughty S, Chu K.L., Faltynek C.R., and Jarvis M.F. Systemic and site-specific effects of A-425619, a selective TRPV1 receptor antagonist, on wide dynamic range neurons in CFA-Treated and uninjured rats. Journal of Neurophysiology, 95, 18-25 (2006).

Skoubis P. D., Hradil V., Chin C-L., Luo Y., Fox G.B., and McGaraughty S. Mapping brain activity following administration of a nicotinic acetylcholine receptor agonist, ABT-594, using functional MRI in awake rats. Neuroscience, 137, 583-591 (2006).

McGaraughty S., Honore P., Wismer C.T., Mikusa J., Zhu C.Z., McDonald H., Bianchi B., Faltynek C.R., and Jarvis M.F. Endogenous Opioid Mechanisms Partially Mediate P2X3 /P2X2/3 -related Antinociception in Rat Models of Inflammatory and Chemogenic Pain but not Neuropathic Pain. British Journal of Pharmacology, 146, 180-188 (2005).

McGaraughty S., Cowart M., Jarvis M.F., and Berman R.S. Anticonvulsant and antinociceptive actions of novel adenosine kinase inhibitors. Review, Current Topics in Medicinal Chemistry, 5, 43-58 (2005).

Chu K.L., Faltynek C.R., Jarvis M.F., and McGaraughty S. Increased WDR spontaneous activity and receptive field size in rats following a neuropathic or inflammatory injury: implications for mechanical sensitivity. Neuroscience Letters, 372, 123-126 (2004).

McGaraughty S., Farr D.A. and Heinricher M.M. Lesions of the periaqueductal gray disrupt input to the rostral ventromedial medulla following microinjections of morphine into the medial or basolateral nuclei of the amygdala. Brain Research, 1009, 223-227 (2004).

McGaraughty S., Wismer C.T., Zhu C., Mikusa J., Honore P., Lee C-H., Chu K.L., Faltynek C.R., and Jarvis M.F. Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration. British Journal of Pharmacology, 140, 1381-1388 (2003).

McGaraughty S., Chu K.L., Bitner R.S., Martino B., El Kouhen R., Han P., Nikkel A.L., Burgard E.C., Faltynek C.R., and Jarvis M.F. Capsaicin infused into the PAG affects rat tail flick responses to noxious heat and alters neuronal firing in the RVM. Journal of Neurophysiology, 90, 2702-2710 (2003).

Jarvis M.F., Mikusa J., Chu K.L., Wismer C.T., Honore P., Kowaluk E.A., and McGaraughty S. Comparison of the ability of adenosine kinase inhibitors and adenosine receptor agonists to attenuate thermal hyperalgesia and reduce motor performance in rats. Pharmacology, Biochemistry and Behavior, 73, 573-581 (2002).

McGaraughty S. and Heinricher M.M. Microinjection of morphine into various amygdaloid nuclei differentially affects nociceptive responsiveness and RVM neuronal activity. Pain, 96, 153-162 (2002).

McGaraughty S., Cowart M., and Jarvis M.F. Recent developments in the discovery of novel adenosine kinase inhibitors: mechanism of action and therapeutic potential. Review, CNS Drug Reviews, 7, 415-432 (2001).

Zhu C.Z., Mikusa J., Chu K.L., Cowart M., Kowaluk E.A., Jarvis M.F., and McGaraughty S. A-134974, a novel adenosine kinase inhibitor, relieves tactile allodynia via spinal sites of action in peripheral nerve injured rats. Brain Research, 905, 104-110 (2001).

McGaraughty S., Chu K.L., Wismer C.T., Mikusa J., Zhu C.Z., Cowart M., Kowaluk E.A. and Jarvis M.F. Effects of A-134974, a novel adenosine kinase inhibitor, on carrageenan-induced inflammatory hyperalgesia and locomotor activity in rats: evaluation of the sites of action. Journal of Pharmacology and Experimental Therapeutics, 296, 501-509 (2001).

Heinricher, M.M., McGaraughty S. and Farr D.A. The role of excitatory amino acid transmission within the rostral ventromedial medulla in the antinociceptive actions of systemically administered morphine. Pain, 81, 57-65 (1999).

Heinricher M.M. and McGaraughty S. Analysis of excitatory amino acid transmission within the rostral ventromedial medulla: implications for circuitry. Pain, 75, 247-255 (1998).

McGaraughty S. and Henry J.L. The effects of strychnine, bicuculline, and ketamine on “immersion-inhibited” dorsal horn convergent neurons in intact and spinalized rats. Brain Research, 784, 63-70 (1998).

McGaraughty S. and Henry J.L. Relationship between mechano-receptive fields of dorsal horn convergent neurons and the response to noxious immersion of the ipsilateral hindpaw in rats. Pain, 70, 133-140 (1997).

McGaraughty S. and Henry J.L. Effects of noxious hindpaw immersion on evoked and spontaneous firing of contralateral dorsal horn convergent neurons in both intact and spinalized rats. Brain Research Bulletin, 43, 263-267 (1997).

McGaraughty S., Reinis S., and Tsoukatos J. A correlogram analysis of the activity in the rostral ventromedial medulla of awake rats and in rats anaesthetized with ketamine or pentobarbital following the administration of morphine. Experimental Brain Research, 106, 283-290 (1995).

McGaraughty S., Reinis S., and Tsoukatos J. Two distinct unit activity responses to morphine in the rostral ventromedial medulla of awake rats. Brain Research, 604, 331-333 (1993).

McGaraughty S., Reinis S., and Tsoukatos J. Investigating the role of anaesthetics on the rostral ventromedial medulla: Implications for a GABAergic link between ON and OFF cells. Neuroscience Letters, 149, 119-122 (1993).

McGaraughty S. and Reinis S. Simultaneous multi- and single unit recording in the rostral ventromedial medulla of ketamine anaesthetized rats and the cross-correlogram analysis of their interactions. Experimental Brain Research, 92, 489-494 (1993).

Reinis S., Weiss D.S., and McGaraughty S. Analysis of real neuronal circuits in the vertebrate central nervous system. Neural Networks, 1-12 (1990).

Selected Research Presentations

Graduate and Post-Doctoral Dermatology Retreat (Washington DC, USA)
Title: An Academic in Industry: Industry Career Path, May 2017

Targeting Pain with Novel Therapeutics (Philadelphia, USA)
Title: Rat Models of Pain-Induced Sleep Disturbance:

An Objective Measure of Non-Evoked Discomfort, June, 2012
(Moderator for additional session on “Models of Pain”) 

Synaptic Plasticity in Pain, King’s College, (London, England)
Title: Purinergic Modulation of Nociception, April, 2007

Spring Pain Research Conference (Cayman Islands).
Title: Administration of a Novel and Selective P2X7 Receptor Antagonist Modulates

Nociceptive Transmission in Neuropathic Rats, April, 2006.
Dept. of Psychology, Brock University, (St. Catharines, Ont. Canada)
Title: Behavioral State and Pain Control, July, 1997 

Dept. of Neurology, University of California at San Francisco (UCSF, USA)
Title: The Neural Circuitry of Environmentally Induced Pain Modulation, March, 1997

Dept. of Psychology, SUNY (Syracuse, N.Y., USA)
Title: Computational Neurodynamics, February, 1995