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 med iator of some persistent pain states. We have used a synthetic protein , trkA-lgG, to sequester endogenous NGF and block the survival effects of NGF on cultured sensory neurons. We show that administration of tr kA-lgC 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-in duced inflammation. These data suggest that peripherally produced NCF normally acts to maintain the sensitivity of nociceptive sensory neuro ns and that, in some inflammatory states, an upregulation of NGF is re sponsible for alterations in pain-related behaviour. Antagonists of NG F may therefore be of clinical use in treating some chronic pain state s.