Publications


Hildebrand ME, Xu J, Dedek A, Li Y, Sengar AS, Beggs S, Lombroso PJ, Salter MW. (2016). Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing.  Cell Rep. 17(10): 2753-65.
URL: https://www.ncbi.nlm.nih.gov/pubmed/27926876

  • In this study, we have uncovered a new mechanism that leads to increased spinal excitation and pain hypersensitivity. We show that two separate spinal mechanisms are actually linked so that taking a foot off the brakes (BDNF-mediated loss of synaptic inhibition) directly causes a stepping on the gas (increase in excitatory NMDAR responses) in dorsal horn neurons after nerve injury. This pathological mechanism may be the root cause of many chronic pain conditions.

Hildebrand ME, Snutch TP.  (2015). The unusual suspects: Regulation of retinal calcium channels by somatostatin.  Channels 9(2):61-2.
URL: http://www.ncbi.nlm.nih.gov/pubmed/25715059


Hildebrand, ME, Pitcher, GM, Harding, EK, Li, H, Beggs, S, Salter, MW. (2014). Dominant GluN2B- and GluN2D-mediated synaptic responses in the adult spinal cord.  Scientific Reports 4: 4094 (12 pages).
URL: http://www.ncbi.nlm.nih.gov/pubmed/24522697

  • In this paper, we characterized the molecular and biophysical properties of synaptic NMDA receptors (NMDARs) in lamina I dorsal horn neurons of the adult rat. Unlike GluN2A-dominated responses at most adult CNS synapses, we found that slow GluN2B- and GluN2D-containing receptors dominate synaptic NMDAR responses at adult lamina I synapses. The results of this study are relevant for both the pain and NMDAR research communities, and it identifies GluN2D as a new potential molecular target for treating pain.

Bourinet, E, Altier, C, Hildebrand, ME, Trang, T., Salter, MW, Zamponi, GW. (2014). Calcium permeable ion channels in pain signaling.  Physiological Reviews 94(1): 81-140. URL: http://www.ncbi.nlm.nih.gov/pubmed/24382884

  • In this comprehensive review, we outline the roles of calcium-permeable ion channels, including voltage-gated calcium channels and synaptic NMDA receptors, in physiological and pathological mechanisms of pain processing, with particular emphasis on peripheral nociceptors and spinal cord dorsal horn neurons.

Isope P, Hildebrand ME, Snutch TP. (2012). Contributions of T-type voltage-gated calcium channels to postsynaptic calcium signalling within Purkinje neurons.  Cerebellum 11(3): 651-665.
http://www.ncbi.nlm.nih.gov/pubmed/20734177


Hildebrand ME, Mezeyova J, Smith PL, Salter MW, Tringham E, Snutch TP. (2011a). Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons.  Molecular Pain 7(1): 67 (13 pages).
http://www.ncbi.nlm.nih.gov/pubmed/21910862

  • Here, we investigated the molecular, biophysical, and pharmacological properties of voltage-gated sodium channels in superficial dorsal horn neurons.  By combining quantitative real-time PCR with the spinal cord slice recording assay, we discovered that the identity and functional properties of voltage-gated sodium channels expressed in the spinal cord dorsal horn is very distinct from those expressed in peripheral pain-sensing neurons.  Thus, dorsal horn sodium channels may represent a promising molecular target for future pain therapeutics.

Hildebrand ME, Smith P, Bladen C, Eduljee C, Xie J, Chen L, Fee-Maki M, Doering C, Mezeyova J, Zhu Y, Belardetti F, Pajouhesh H, Parker D, Parmar M, Porreca F, Tringham E, Zamponi G, Snutch TP. (2011b). A novel slow inactivation specific ion channel modulator attenuates neuropathic pain.  Pain 152(4): 833-843.
http://www.ncbi.nlm.nih.gov/pubmed/21349638

  • As part of a multidisciplinary preclinical research team at Zalicus Pharmaceuticals, we identified a novel class of analgesics that potently reverse chronic pain by acting on pathological states of excitatory voltage-gated channels. This paper is part of a shift in the ion channel drug discovery field from a sole focus on specificity against individual channel subtypes to specificity against pathological function across channel classes.