| First Author | Liu XJ | Year | 2008 |
| Journal | Nat Med | Volume | 14 |
| Issue | 12 | Pages | 1325-32 |
| PubMed ID | 19011637 | Mgi Jnum | J:142227 |
| Mgi Id | MGI:3820752 | Doi | 10.1038/nm.1883 |
| Citation | Liu XJ, et al. (2008) Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex. Nat Med 14(12):1325-32 |
| abstractText | 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. |
