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A M Ritter

Publications and source records attributed to A M Ritter.

22 records · Page 2Linked to original sources

Somal membrane properties of physiologically identified sensory neurons in the rat: effects of nerve growth factor.

1. Intracellular recordings were made in situ from physiologically identified dorsal root ganglion (DRG) cells in untreated rats aged 5-8 wk and in rats treated from birth to 5 wk of age with nerve growth factor (NGF) or antisera against NGF (anti-NGF). 2. As demonstrated in cats, the shape of the somal action potential (AP) of DRG cells of normal rats is correlated with peripheral receptor type. Cells that innervate high-threshold mechanoreceptors (HTMRs) and thus respond to noxious stimulation of skin or deep tissue in the periphery have long-duration APs characterized by an inflection on the falling limb of the spike. Cells that innervate low-threshold mechanoreceptors (LTMRs) have briefer APs that lack the inflection. Somal APs of neurons supplying HTMRs tend to be larger in amplitude, have slower peak rates of rise, and on average have longer afterhyperpolarizations than those innervating LTMRs. 3. It was also found that the somal APs of HTMRs were not blocked by 200 microM tetrodotoxin (TTX) applied directly to the surface of the ganglion. In contrast, those of LTMRs were rapidly and irreversibly blocked. Despite the difference in the sensitivity of the soma, axonal conduction in both types of cells was abolished by TTX. 4. Chronic treatment with NGF resulted in an increase in duration of the falling limb of the spike compared with untreated control animals or animals treated with preimmune rabbit serum. This was true only in cells that had long duration APs to begin with, i.e., HTMRs. LTMRs were unaffected by the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

On the role of nerve growth factor in the development of myelinated nociceptors.

We have previously demonstrated that administration of antisera against NGF (anti-NGF) can have profound effects on developing primary afferents (Ritter et al., 1991). Chronic administration of anti-NGF to rats beginning on the day of birth results in a severe depletion of cutaneous A delta high-threshold mechanoreceptors (HTMRs) from the sural nerve. Here we have carried out further experiments in order to define the period of time over which this change in the cutaneous afferent population can be produced, and to investigate a possible mechanism for the change. Treatment with anti-NGF from postnatal day (PND) 0-14 resulted in a depletion of cutaneous A delta HTMRs from the sural nerve and also a 20% loss of sensory neurons. However, treatment from PND 2-14 produced an identical deficit of HTMRs without any accompanying cell death. Thus, the depletion of cutaneous A delta HTMRs can be achieved in the absence of cell death induced by anti-NGF treatment. It was also found that a 7 d treatment from PND 4-11 was sufficient to reproduce this effect, but that 7 d treatments earlier (PND 2-9) or later (PND 7-14) within the first 2 weeks were much less effective. This critical period, PND 4-11, corresponds to a period of anatomical change in the innervation of the skin, from epidermal innervation to primarily dermal innervation (Fitzgerald, 1967; Reynolds et al., 1991). In every case where anti-NGF treatment reduced the proportion of HTMRs, there was a reciprocal increase in the proportion of sensitive A delta hair follicle (D-hair) afferents. We hypothesize that in the absence of NGF, developing cutaneous A delta HTMRs do not die but innervate novel targets in the dermis and become D-hair afferents instead.

Animals↗

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

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.

Afferent Pathways↗