title: A synthetic cell-penetrating peptide antagonizing TrkA function suppresses neuropathic pain in mice.
abstract: Nerve growth factor (NGF) and its high-affinity receptor, TrkA, are one of the targets in the production of new drugs for the treatment of neuropathic pain. NGF contributes to both the initiation and maintenance of sensory abnormalities after peripheral nerve injury. This study examined the effects of IPTRK3, a new synthetic cell-penetrating peptide that antagonizes TrkA function, on neuropathic pain in mice. Partial sciatic nerve ligation (PSNL) was used to generate neuropathic pain, and we injected IPTRK3 (2 or 10 mg/kg) intraperitoneally on day 7 after PSNL. Effects of the peptide on hyperalgesia, allodynia, and expression of Fos in the spinal cord were examined. Single administration of the peptide on day 7 significantly suppressed both thermal hyperalgesia and mechanical allodynia. Gentle touch stimuli-evoked Fos expression in the lumbar spinal cord was also significantly reduced. Intraperitoneal injection of a cell-penetrating peptide antagonizing TrkA function appears effective for treatment of neuropathic pain in a mouse pain model.
authors: Department of Anesthesiology and Reanimatology, University of Fukui, Faculty of Medical Sciences, Japan.
authors: Wei-Ying
authors: WY
authors: Ma
authors: Eri
authors: E
authors: Murata
authors: Koyo
authors: K
authors: Ueda
authors: Yoshihiro
authors: Y
authors: Kuroda
authors: Ming-Hui
authors: MH
authors: Cao
authors: Mineo
authors: M
authors: Abe
authors: Kenji
authors: K
authors: Shigemi
authors: Munetaka
authors: M
authors: Hirose
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D020917:Receptor, trkA / Q000037:antagonists & inhibitors* / Q000502:physiology*
chemical_list: D057846:Cell-Penetrating Peptides; D016761:Oncogene Proteins v-fos; D020917:Receptor, trkA