The University of Toronto Centre for the Study of Pain

124 Edward Street

Room 374

Toronto, Ontario

M5G 1G6

Tel: 416-979-4762

Fax: 416-979-4936

pain.director@utoronto.ca

UTCSP External Review Reports Now Available On-line

The University of Toronto Centre for the Study of Pain underwent an External Review in early October, 2008.  The review team consisted of Dr. Troels Jensen, Director of the Danish Pain Research Centre at Aarhus University Hospital, Denmark, immediate past-President of the International Association for the Study of Pain, and Dr. Mary Ellen Jeans, President & CEO of Associated Medical Services, former CEO of the Canadian Nurses Association and former Director of the School of Nursing at McGill University. A PDF of the UTCSP External Review Report, along with the reviewer’s report is now available:  UTCSP External Review Report 2008; Reviewer's Report of the UTCSP

Salter team reports discovery of a novel approach to treating chronic pain by blocking an intracellular protein interaction in the central nervous system


Mike Salter’s research team has developed a peptide for treating pain by blocking an intracellular protein interaction in the central nervous system (CNS). The team’s findings are reported in the December issue of Nature Medicine. The conventional understanding is that chronic pain hypersensitivity is dependent upon N-methyl-D-aspartate receptors (NMDARs), a main subtype of glutamate receptor mediating communication between neurons in the CNS.  However, treating chronic pain through the use of NMDAR blocking drugs is limited because NMDARs are essential for many key physiological functions. Salter’s team discovered that pain hypersensitivity depends upon amplification of the function of NMDARs by the protein tyrosine kinase Src. Using rodent models, the team designed a peptide that, when given intravenously, is able to prevent the action of Src to amplify NMDAR function. This was achieved by designing the peptide to disrupt the interaction between two proteins, Src and NADH dehydrogenase subunit 2 (ND2), which anchors Src to NMDAR.  Salter’s team shows that the peptide selectively inhibits the amplification of NMDAR that produces chronic pain, without affecting physiological functions of the receptor. As the peptide suppressed pain behaviours in models of both inflammatory and neuropathic pain but did not affect acute, nociceptive pain behaviours, this approach is potentially of broad use for chronic pain disorders.

Pain in the News

2009-06-16 : Transient receptor potential vanilloid subtype 1 (TRPV1) is activated by low pH / protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1) activation....
2009-06-15 : Functional imaging has revolutionized the neurosciences. In the pain field it has dramatically altered our understanding of how the brain undergoes significant functional, anatomical and chemical changes in patients with chronic pain....
2009-06-11 : Long-term potentiation (LTP), a much studied cellular model of synaptic plasticity, has not been demonstrated at synapses between primary afferent C-fibers and spinal dorsal horn (DH) neurons in mice in vivo. EphrinB-EphB receptor signaling plays important roles in synaptic connection and plasticity in the nervous system, but its role in spinal synaptic plasticity remains unclear....
2009-06-10 : A growing body of evidence indicates that P2X receptors (P2XRs), a family of ligand-gated cation channels activated by extracellular ATP, play an important role in pain signaling. In contrast to the role of the P2X3R subtype that has been extensively studied, the precise roles of others among the seven P2XR subtypes (P2X1R-P2X7R) remain to be determined because of a lack of sufficiently powerful tools to specifically block P2XR signaling in vivo....
2009-06-06 : The mammalian target of rapamycin (mTOR) is a key regulator of protein translation whose action can be inhibited by the drug rapamycin. Forms of long-term plasticity require protein synthesis and evidence indicates that mRNA in dendrites, axon terminals and cell bodies is essential for long-term synaptic plasticity....
2009-05-27 : Inflammatory processes play important roles in both neuropathic and inflammatory pain states, but the effects of inflammation per se within the sensory ganglia are not well understood. The cytokine growth-related oncogene (GRO/KC; CXCL1) shows strong, rapid upregulation in dorsal root ganglion (DRG) in both nerve injury and inflammatory pain models....