Requirement for nerve growth factor in the development of myelinated nociceptors in vivo

Abstract

In adult animals, sensory neurons innervating the skin are phenotypically diverse. We have now investigated whether nerve growth factor (NGF) has a physiological role in the development of this diversity. We gave antisera against NGF to rats from postnatal day 1 (PND 1) to adulthood (5 weeks). We found a virtually complete depletion of high threshold mechanoreceptors conducting in the A delta range (2-13 ms-1) in the sural nerve. This afferent type, normally present in large numbers, appeared to have been replaced by D-hair afferents, sensitive mechanoreceptors which normally are relatively rare. NGF deprivation had this effect only in early postnatal life; treatment from postnatal day 14 to adulthood had no effect. We conclude that the presence of NGF postnatally in skin is necessary for the proper phenotypic development of A delta cutaneous nociceptors.

Exogenous nerve growth factor attenuates opioid-induced inhibition of voltage-activated Ba2+ currents in rat sensory neurons

“…Postnatally NGF continues to be expressed by target tissues such as the skin, and this endogenous NGF maintains the nociceptor phenotype of afferents innervating the tissue. In postnatal animals, for example, sequestration of endogenous NGF using anti-NGF antiserum or a TrkA-IgG fusion protein causes loss of nociceptor function (Ritter et al, 1991;Lewin and Mendell, 1994;McMahon et al, 1995;Bennett et al, 1998). Experimentally increasing levels of NGF in the skin, either by administration of exogenous NGF or in transgenic mice selectively overexpressing NGF in skin, enhances the sensitivity of nociceptors to noxious stimuli (Lewin et al, 1993;Lewin and Mendell, 1994;Rueff and Mendell, 1996;.…”

“…A large number of nociceptive neurons remain sensitive to NGF postnatally, and in adult animals NGF plays a role in both physiological and pathological pain conditions. In the resting state, low levels of NGF are needed for the expression of nociceptor markers such as the neuropeptides substance P and calcitonin-gene-related peptide (CGRP; Molliver and Snider, 1997;Patel et al, 2000), and for nociceptive afferents to retain their ability to respond to noxious stimuli (Ritter et al, 1991;Lewin and Mendell, 1994;McMahon et al, 1995;Bennett et al, 1998 (Donnerer et al, 1992;Woolf et al, 1994;McMahon et al, 1995;Koltzenburg et al, 1999).…”

Nerve Growth Factor and Nociception: From Experimental Embryology to New Analgesic Therapy

“…A classic example of algogen induced heat and mechanical hyperalgesia is that following application of capsaicin to the skin (LaMotte et al, 1991). While working on the role of NGF in determining the phenotypic identity of nociceptors in Lorne Mendell's lab (Ritter et al, 1991;Lewin et al, 1992a), Amy Ritter and Gary Lewin noted that rats that had been exposed to daily injections of NGF were behaviorally more sensitive to mechanical and heat stimuli than untreated animals. These observations led them to make a more systematic study of the effects of NGF on nociceptive behaviors in the rat.…”

, NGF - Induced Changes in Adrenergic Modulation of Calcium Channels of Trigeminal Ganglion Neurons

“…Фактор росту нервової тканини (ФРНТ) -це пептид з сімейства нейротрофінів, який необхідний для розвитку і підтримування життєдіяльності симпатичних і сенсорних нейронів [10,11]. Концентрація ФРНТ підвищується у міжклітинному просторі у відповідь на ушкодження периферичних нервів.…”