α1‐Antitrypsin derived SP16 peptide demonstrates efficacy in rodent models of acute and neuropathic pain

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 inflammat...

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Bibliographic Details
Published in:The FASEB journal 2022-01, Vol.36 (1), p.e22093-n/a
Main Authors: Wang, Zixuan, Martellucci, Stefano, Van Enoo, Alicia, Austin, Dana, Gelber, Cohava, Campana, Wendy M.
Format: Article
Language:English
Subjects:
Acute Pain - chemically induced
Acute Pain - drug therapy
Acute Pain - genetics
Acute Pain - metabolism
alpha 1-Antitrypsin - chemistry
alpha 1-Antitrypsin - genetics
Animals
Disease Models, Animal
Low Density Lipoprotein Receptor-Related Protein-1 - genetics
Low Density Lipoprotein Receptor-Related Protein-1 - metabolism
LRP1
Male
MAP Kinase Signaling System
Mice
Neuralgia - chemically induced
Neuralgia - drug therapy
Neuralgia - genetics
Neuralgia - metabolism
Neurites - metabolism
neuroinflammation
neuropathic pain
nociception
PC12 Cells
Peptides - chemistry
Peptides - pharmacology
peripheral nerve injury
Rats
Rats, Sprague-Dawley
Schwann Cells - metabolism
Sensory Receptor Cells - metabolism
SP16
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Summary: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 
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.202101031RR