151. α1‐Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain
- Author
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Wang, Zixuan, Martellucci, Stefano, Van Enoo, Alicia, Austin, Dana, Gelber, Cohava, and Campana, Wendy M
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Clinical Sciences ,Neurodegenerative ,Pain Research ,Peripheral Neuropathy ,Chronic Pain ,Aetiology ,2.1 Biological and endogenous factors ,Acute Pain ,Animals ,Disease Models ,Animal ,Low Density Lipoprotein Receptor-Related Protein-1 ,MAP Kinase Signaling System ,Male ,Mice ,Neuralgia ,Neurites ,PC12 Cells ,Peptides ,Rats ,Rats ,Sprague-Dawley ,Schwann Cells ,Sensory Receptor Cells ,alpha 1-Antitrypsin ,LRP1 ,neuroinflammation ,neuropathic pain ,nociception ,peripheral nerve injury ,SP16 ,Biochemistry and Cell Biology ,Physiology ,Medical Physiology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical physiology - Abstract
SP16 is an innovative peptide derived from the carboxyl-terminus of α1-Antitrypsin (AAT), corresponding to residues 364-380, and contains recognition sequences for the low-density lipoprotein receptor-related protein-1 (LRP1). LRP1 is an endocytic and cell-signaling receptor that regulates inflammation. Deletion of Lrp1 in Schwann cells increases neuropathic pain; however, the role of LRP1 activation in nociceptive and neuropathic pain regulation remains unknown. Herein, we show that SP16 is bioactive in sensory neurons in vitro. Neurite length and regenerative gene expression were increased by SP16. In PC12 cells, SP16 activated Akt and ERK1/2 cell-signaling in an LRP1-dependent manner. When formalin was injected into mouse hind paws, to model inflammatory pain, SP16 dose-dependently attenuated nociceptive pain behaviors in the early and late phases. In a second model of acute pain using capsaicin, SP16 significantly reduced paw licking in both male and female mice (p
- Published
- 2022