The VGF-derived peptide TLQP-21: a new modulatory peptide for inflammatory pain.
Vgf, is a neuro-endocrine specific gene encoding for a large protein precursor of different peptides. A role for VGF in pain modulation has been suggested from immunohistochemical studies showing VGF mRNA widely expressed in primary sensory neurons. In this study, the presence of VGF on the primary sensory afferents in mice was confirmed by showing its immunostaining in cultured neurons of dorsal root ganglia in secretory granule varicosities colocalized with Substance P. Moreover, the functional role of a C-terminal internal VGF-derived peptide, i.e. TLQP-21, was assessed by investigating its peripheral (1, 2, 4, 8mM) and central (1, 2, 4 mM) effects on inflammatory pain in the formalin test. A significant increase of pain-related licking response following peripheral injection of TLQP-21 (4 and 8mM) was observed in the second inflammatory phase of the test. In addition, an increase in licking response was detected when 4 mM of the peptide was injected alone without formalin. On the other hand, the central administration of TLQP-21 induced an U-shaped curve, with the dose of 2 mM being analgesic during the second phase. This study shows for the first time that a VGF-derived peptide may be involved in inflammatory pain in vivo and demonstrates a different action for TLQP21 at the peripheral and central levels of the nociceptive pathways.
Rizzi
Roberto
R
CNR, Institute of Neuroscience, Rome, Italy.
Bartolomucci
Alessandro
A
Moles
Anna
A
D'Amato
Francesca
F
Sacerdote
Paola
P
Levi
Andrea
A
La Corte
Giorgio
G
Ciotti
Maria Teresa
MT
Possenti
Roberta
R
Pavone
Flaminia
F
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D007249:Inflammation / Q000150:complications*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage*; D013373:Substance P / Q000378:metabolism
D009414:Nerve Growth Factors; D009479:Neuropeptides; D010446:Peptide Fragments; C522412:TLQP-21 peptide; C512697:Vgf protein, mouse; D013373:Substance P