The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule.
Evidence suggests that nerve growth factor (NGF) may function as a mediator of some persistent pain states. We have used a synthetic protein, trkA-IgG, to sequester endogenous NGF and block the survival effects of NGF on cultured sensory neurons. We show that administration of trkA-IgG produces a sustained thermal and chemical hypoalgesia and leads to a downregulation of the sensory neuropeptide CGRP (calcitonin gene-related peptide) in treated sensory neurons. Acute administration of the molecule blocks the hyperalgesia that develops with carrageenan-induced inflammation. These data suggest that peripherally produced NGF normally acts to maintain the sensitivity of nociceptive sensory neurons and that, in some inflammatory states, an upregulation of NGF is responsible for alterations in pain-related behaviour. Antagonists of NGF may therefore be of clinical use in treating some chronic pain states.
McMahon
S B
SB
Department of Physiology, United Medical School, St Thoma's Campus, London, UK.
Bennett
D L
DL
Priestley
J V
JV
Shelton
D L
DL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D007074:Immunoglobulin G; D007249:Inflammation / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D007074:Immunoglobulin G; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; D002351:Carrageenan; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin