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Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex.

Liu, XJ; Gingrich, JR; Vargas-Caballero, M; Dong, YN; Sengar, A; Beggs, S; Wang, S-H; ... Salter, MW; + view all (2008) Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nat Med , 14 (12) pp. 1325-1332. 10.1038/nm.1883.

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Abstract

Chronic pain hypersensitivity depends on N-methyl-D-aspartate receptors (NMDARs). However, clinical use of NMDAR blockers is limited by side effects resulting from suppression of the physiological functions of these receptors. Here we report a means to suppress pain hypersensitivity without blocking NMDARs, but rather by inhibiting the binding of a key enhancer of NMDAR function, the protein tyrosine kinase Src. We show that a peptide consisting of amino acids 40-49 of Src fused to the protein transduction domain of the HIV Tat protein (Src40-49Tat) prevented pain behaviors induced by intraplantar formalin and reversed pain hypersensitivity produced by intraplantar injection of complete Freund's adjuvant or by peripheral nerve injury. Src40-49Tat had no effect on basal sensory thresholds, acute nociceptive responses or cardiovascular, respiratory, locomotor or cognitive functions. Thus, through targeting of Src-mediated enhancement of NMDARs, inflammatory and neuropathic pain are suppressed without the deleterious consequences of directly blocking NMDARs, an approach that may be of broad relevance to managing chronic pain.

Type: Article
Title: Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex.
Location: United States
DOI: 10.1038/nm.1883
Keywords: Animals, Behavior, Animal, Formaldehyde, Gene Products, tat, Inflammation, Learning, Mice, Nervous System Diseases, Pain, Peptides, Protein Binding, Rats, Receptors, N-Methyl-D-Aspartate, src-Family Kinases
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/1496658
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