PHARMACOLOGY FACULTY
Selected Publications
  • Khan AA, Diogenes A, Jeske NA, Henry MA, Akopian A, Hargreaves KM. Tumor necrosis factor alpha enhances the sensitivity of rat trigeminal neurons to capsaicin. Neuroscience 155(2):503-9, 2008.
  • Jeske NA, Diogenes A, Ruparel NB, Fehrenbacher JC, Henry M, Akopian AN, Hargreaves KM. A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 138(3):604-16, 2008.
  • Akopian AN, Ruparel NB, Jeske NA, Hargreaves KM. Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization. J Physiol 15;583(Pt 1):175-93, 2007.
  • Jeske NA, Patwardhan AM, Gamper N, Price TJ, Akopian AN, Hargreaves KM. Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem 27;281(43):32879-90, 2006.
  • Diogenes A, Patwardhan AM, Jeske NA, Ruparel NB, Goffin V, Akopian AN, Hargreaves KM. Prolactin modulates TRPV1 in female rat trigeminal sensory neurons. J Neurosci 2;26(31):8126-36, 2006.
  • Patwardhan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM. The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA 25;103(30):11393-8, 2006.
  • Jeske NA, Berg KA, Cousins JC, Ferro ES, Clarke WP, Glucksman MJ, Roberts JL. Modulation of bradykinin signaling by EP24.15 and EP24.16 in cultured trigeminal ganglia. J Neurochem 97(1):13-21, 2006.
  • Patwardhan AM, Berg KA, Akopian AN, Jeske NA, Gamper N, Clarke WP, Hargreaves KM. Bradykinin-induced functional competence and trafficking of the delta-opioid receptor in trigeminal nociceptors. J Neurosci 28;25(39):8825-32, 2005.
  • Price TJ, Jeske NA, Flores CM, Hargreaves KM. Pharmacological interactions between calcium/calmodulin-dependent kinase II alpha and TRPV1 receptors in rat trigeminal sensory neurons. Neurosci Lett 2;389(2):94-8, 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 or BDNF: Effects on neuronal survival, neurochemical properties and TRPV1-mediated neuropeptide secretion. BMC Neurosci 24;6:4, 2005.
  • Jeske NA, Glucksman MJ, Roberts JL. Metalloendopeptidase EC3.4.24.15 is constitutively released from the exofacial leaflet of lipid rafts in GT1-7 cells. J Neurochem 90(4):819-28, 2004.
  • Jeske NA, GLucksman MJ, Roberts JL. EP24.15 is associated with lipid rafts. J Neurosci Res 1;74(3):468-73.
Nathaniel Jeske
 

Nathaniel Jeske

Assistant Professor of Oral & Maxillofacial Surgery
Ph.D., UTHSCSA

Office: 210-567-3466
Email: jeske@uthscsa.edu

 

Keywords

pain, TRPV1, AKAP, inflammation, ECM

 

Research Summary

Inflammatory hyperalgesia comprises a physiological condition by which injury results in the accumulation of biochemical mediators that sensitize primary pain-sensing neurons (nociceptors) to depolarize in response to reduced activation thresholds. Nociceptor sensitization primarily occurs through the stimulation of signaling pathways that can phosphorylate certain receptor channels that are acitvated by pain-causing stimuli. In the case of the receptor channel TRPV1, which is activated by capsaicin, heat, low pH, and certain cannabinoids, among other stimuli, phosphorylation significantly sensitizes the channel. Hence, inflammatory mediators that stimulate kinase signaling cascades in response to injury, results in the phosphorylation and sensitization of TRPV1, comprising a major component of inflammatory hyperalgesia.


In the Jeske lab, we are working to characterize specific signaling events that are critical to the phosphorylation of TRPV1. Several of our studies are focused on the biochemical, molecular, and pharmacological dissection of the AKAP scaffolding protein, and its role in targeting kinases to TRPV1. The interaction of the AKAP scaffolding protein and TRPV1 in regards to inflammatory sensitization provides an interesting perspective by which analgesic pharmacotherapeutic options can be developed. The other focus of our research group involves characterizing the sensitizing roles of extracellular matrix molecules (fibronectin, collagen, laminin, etc.) on TRPV1 activity and pain perception, especially in the orofacial cavity and associated tissues. Unique access to normal and diseased human biopsies through Oral and Maxillofacial clinic association, in conjunction with the utilization of physiologically-relevant primary neuronal cultures and modifiable immortalized cell lines, provides important and appropriate models for studying the biochemical modulation of inflammatory hyperalgesia.