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Patrick Sheets, PhD

Assistant Professor of Pharmacology & Toxicology
Stark Neurosciences Research Center

Research Interest  


The goal of my laboratory’s work is to identify the neural mechanisms through which inflammatory and neuropathic pain alters circuit function in cognitive and emotional networks of the brain thereby producing critical knowledge regarding the affective dimension of pain and pain disorders that could lead to novel strategies for therapeutic intervention. 


Education
 

 

2012

Postdoctoral Fellow, Neurobiology
Northwestern University

Chicago, IL 
 

2007

PhD, Pharmacology
Indiana University

Indianapolis, IN 
 

2003

M.S., Toxicology
Purdue University

West Lafayette, IN 
 

2001

B.S., Health Sciences
Purdue University

West Lafayette, IN 
 

Honors and Awards
 

 
 

2002

Distinguished Student Award Academic Excellence
Purdue University
 

2005

Best Poster Award
Indianapolis Society for Neuroscience
 

2005

Paul and Carole Stark Research Fellowship
IU School of Medicine
 

2006

Society for Neuroscience Travel Award
 

2007

Travel Award for Outstanding Abstract
Indiana University
 

2007

KK Chen Fellowship
IU School of Medicine
Department of Pharmacology & Toxicology
 

2008‒2010

Institutional National Research Award
T32 Trainee
Northwestern-NIH
 

2010‒2012

National Research Award
F32 Postdoctoral
NIH
 

2014‒2015

Leadership in Academic Medicine Program
Trainee
IU School of Medicine 
 

Elucidating Alterations to Supraspinal Circuitry Caused by Neuropathic and Inflammatory Pain

 

The major objective of my laboratory is to understand the mechanisms by which neuropathic and inflammatory pain alter the morphology, intrinsic physiology, neuromodulation, and connectivity of circuitry encompassing the medial prefrontal cortex (mPFC), periaqueductal gray (PAG), and amygdala. Importantly, circuits comprising the mPFC are essential in processing emotional components of our everyday experiences, and therefore, are implicated in the affective component, or unpleasantness, of pain. Additionally, mPFC circuits are associated with depression and anxiety which are common co-morbidities of neuropathic pain.
 

The PAG is a link in the primary pain-modulating network essential for endogenous analgesia and autonomic response to pain. In humans, the mPFC-PAG pathway is associated with emotional modulation of pain. The amygdala serves as a key node that integrates information essential for connecting pain and emotion. Signaling of reciprocal pathways between the PAG and amygdala is critical for neuronal processing involved in nociception. However, virtually nothing is known regarding 1) the functional organization of local or long-range inputs of mPFC-PAG-amygdala circuits and 2) the specific mechanisms by which neuropathic and inflammatory pain alter the neurophysiology and synaptic function of mPFC-PAG-amygdala circuitry. These are critical unknowns that need to be resolved for understanding the mechanisms that drive dysfunction of neural activity in neuropathic and inflammatory pain.
 

Our lab is currently using a multifaceted approach (retrograde labeling, slice electrophysiology, laser scanning photostimulation, high resolution imaging, optogenetics, behavior) to resolve these critical unknowns. The rationale for our work is that identifying the neural mechanisms through which neuropathic and inflammatory pain alters circuit function in cognitive and emotional networks of the brain (specifically mPFC-PAG-amygdala) will produce critical knowledge regarding the affective and emotional dimensions of pain. Such an understanding can lead to novel strategies for therapeutic intervention and improvement of clinical guidelines.

  • Cheriyan J, Kaushik M, Ferreira AN, Sheets PL (2016) Specific targeting of the basolateral amygdala to projectionally defined pyramidal neurons in prelimbic and infralimbic cortex. eNeuro. Mar 31; 3(2). PMID: 27022632.

  • Ferreira AN, Yousuf H, Dalton S, Sheets PL. Highly differentiated cellular and circuit properties of infralimbic pyramidal neurons projecting to the periaqueductal gray and amygdala. Frontiers in cellular neuroscience. 2015; 9:161. PubMed [journal] PMID: 25972785, PMCID: PMC4412064
     
  • Ploplis VA, Donahue DL, Sandoval-Cooper MJ, MorenoCaffaro M, Sheets P, Thomas SG, Walsh M, Castellino FJ. Systemic platelet dysfunction is the result of local dysregulated coagulation and platelet activation in the brain in a rat model of isolated traumatic brain injury. Journal of neurotrauma. 2014; 31(19):1672-5. PubMed [journal] PMID: 24605991, PMCID: PMC4170810
     
  • Balsara RD, Ferreira AN, Donahue DL, Castellino FJ, Sheets PL. Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in cortical neurons. Neuropharmacology. 2014; 79:542-9. NIHMSID: NIHMS556486 PubMed [journal] PMID: 24440368, PMCID: PMC3951114
     
  • Yasvoina MV, Genç B, Jara JH, Sheets PL, Quinlan KA, Milosevic A, Shepherd GM, Heckman CJ, Özdinler PH. eGFP expression under UCHL1 promoter genetically labels corticospinal motor neurons and a subpopulation of degeneration-resistant spinal motor neurons in an ALS mouse model. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013; 33(18):7890-904. NIHMSID: NIHMS560680 PubMed [journal] PMID: 23637180, PMCID: PMC3963467
     
  • Sheets PL, Suter BA, Kiritani T, Chan CS, Surmeier DJ, Shepherd GM. Corticospinal-specific HCN expression in mouse motor cortex: I(h)-dependent synaptic integration as a candidate microcircuit mechanism involved in motor control. Journal of neurophysiology. 2011; 106(5):2216-31. PubMed [journal] PMID: 21795621, PMCID: PMC3214092
     
  • Brittain MK, Brustovetsky T, Sheets PL, Brittain JM, Khanna R, Cummins TR, Brustovetsky N. Delayed calcium dysregulation in neurons requires both the NMDA receptor and the reverse Na+/Ca2+ exchanger. Neurobiology of disease. 2012; 46(1):109-17. NIHMSID: NIHMS349396 PubMed [journal] PMID: 22249110, PMCID: PMC3299854
     
  • Sheets PL, Jarecki BW, Cummins TR. Lidocaine reduces the transition to slow inactivation in Na(v)1.7 voltage-gated sodium channels. British journal of pharmacology. 2011; 164(2b):719-30. PubMed [journal] PMID: 21232038, PMCID: PMC3188891
     
  • Sheets PL, Shepherd GM. Cortical circuits for motor control. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2011; 36(1):365-6. PubMed [journal] PMID: 21116259, PMCID: PMC3055514
     
  • Brustovetsky T, Brittain MK, Sheets PL, Cummins TR, Pinelis V, Brustovetsky N. KB-R7943, an inhibitor of the reverse Na+ /Ca2+ exchanger, blocks N-methyl-D-aspartate receptor and inhibits mitochondrial complex I. British journal of pharmacology. 2011; 162(1):255-70. PubMed [journal] PMID: 20883473, PMCID: PMC3012420
     
  • Anderson CT, Sheets PL, Kiritani T, Shepherd GM. Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex. Nature neuroscience. 2010; 13(6):739-44. NIHMSID: NIHMS191728 PubMed [journal] PMID: 20436481, PMCID: PMC2876193
     
  • Jarecki BW, Sheets PL, Xiao Y, Jackson JO 2nd, Cummins TR. Alternative splicing of Na(V)1.7 exon 5 increases the impact of the painful PEPD mutant channel I1461T. Channels (Austin, Tex.). 2009; 3(4):259-67. NIHMSID: NIHMS181945 PubMed [journal] PMID: 19633428, PMCID: PMC2856339
     
  • Jarecki BW, Sheets PL, Jackson JO 2nd, Cummins TR. Paroxysmal extreme pain disorder mutations within the D3/S4-S5 linker of Nav1.7 cause moderate destabilization of fast inactivation. The Journal of physiology. 2008; 586(17):4137-53. PubMed [journal] PMID: 18599537, PMCID: PMC2652197
     
  • Yu J, Anderson CT, Kiritani T, Sheets PL, Wokosin DL, Wood L, Shepherd GM. Local-Circuit Phenotypes of Layer 5 Neurons in Motor-Frontal Cortex of YFP-H Mice. Frontiers in neural circuits. 2008; 2:6. PubMed [journal] PMID: 19129938, PMCID: PMC2614859
     
  • Kondo T, Sheets PL, Zopf DA, Aloor HL, Cummins TR, Chan RJ, Hashino E. Tlx3 exerts context-dependent transcriptional regulation and promotes neuronal differentiation from embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America. 2008; 105(15):5780-5. PubMed [journal] PMID: 18391221, PMCID: PMC2311353
     
  • Sheets PL, Heers C, Stoehr T, Cummins TR. Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics. 2008; 326(1):89-99. PubMed [journal] PMID: 18378801
     

 

 


Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202