Maturational changes in sympathetic and sensory innervation of the rat uterus: Effects of neonatal capsaicin treatment

Abstract

The plasticity of the sympathetic and sensory innervation of the rat uterus was examined, before and after puberty, in controls and in animals where primary sensory nerves had been destroyed by neonatal capsaicin treatment. Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows: (1) Puberty was associated with a marked increase in the weight of the uterine horn, uterine cervix and parametrial tissue. This was unaffected by capsaicin treatment. (2) The sympathetic innervation of the uterine horn and parametrial tissue was reduced following puberty as revealed by a decrease in the density of noradrenaline-containing nerves and a marked decrease in the tissue concentration of noradrenaline. Sympathetic nerves supplying the uterine cervix and the blood vessels of the uterus appeared to be unaffected by puberty. (3) In contrast, the sensory supply of the uterus by substance P and calcitonin gene-related peptide-containing nerves increased in parallel with uterine growth during puberty resulting in no change in nerve density and only a slight reduction in peptide concentration. (4) Neonatal capsaicin treatment caused a long-lasting depletion of substance P- and calcitonin gene-related peptide-containing nerves. In the uterine horn and parametrial tissue, capsaicin-resistant calcitonin gene-related peptide, but not substance P, still increased with tissue weight during puberty, indeed, in the uterine horn, the relative increase was greater than in controls. (5) Sensory denervation resulted in an increase in the non-vascular sympathetic supply of the uterus, although there was a regional variation in the time course of the response. Perivascular sympathetic nerves were unaffected by capsaicin treatment. The pattern of change in non-vascular noradrenaline-containing nerves associated with puberty was similar in nature to controls. Thus, there is considerable plasticity in the innervation of the uterus both during puberty and following sensory denervation. A complex pattern of change occurs with differential responses in vascular and nonvascular nerves and in different regions of the uterus. Such differences may be due in part to the different origins of individual nerve populations and/or to their relative sensitivities to sex hormones.

Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA

“…Similarly, sympathectomy results in an increase in the density of sensory nerves and neuropeptide levels (Allen et al 1985;Van Ranst and Lauweryns 1990;Aberdeen et al 1990;Mione et al 1992). Our current studies show that neither the pattern nor the density of uterine CGRP-I nerves is affected by sympathectomy, thus confirming previous findings showing that sympathectomy did not increase the levels of CGRP and substance P in the uterus (Brauer et al 1994b). Even more relevant, the current results indicate that sympathectomy does not increase the growth rate of uterine sensory nerves following chronic oestrogen treatment, indicating that uterine sensory nerves are less responsive to sympa- Table 3 Summary of (a) the effects of chronic oestrogen treatment (COT) on TrkA fluorescence intensity (grey level) in small and medium-sized Fluorogold-labelled uterine-projecting neurons of T13 and L1 dorsal root ganglia and (b) oestrogen-induced changes in the number of medium-sized neurons displaying low (less than 80 linear optical density units, LODU) and high (more than 80 LODU) TrkA fluorescence intensity.…”

“…For instance, increased density of sympathetic nerves and noradrenaline levels has been shown following removal of sensory nerves in different peripheral targets, including the uterus (Terenghi et al 1986;Luthman et al 1989;Brauer et al 1994b;Sann et al 1995). Similarly, sympathectomy results in an increase in the density of sensory nerves and neuropeptide levels (Allen et al 1985;Van Ranst and Lauweryns 1990;Aberdeen et al 1990;Mione et al 1992).…”

Effects of chronic and acute oestrogen treatment on the developing noradrenaline‐containing nerves of the rat uterus

“…NA levels were measured in the isolated whole uterine horn, parametrial tissue and uterine cervix by high performance liquid chromatography with electrochemical detection, as previously reported. [2][3][4]13 For comparative purposes the content of NA was measured in the urinary bladder and right auricle following chronic oestrogen treatment. NA levels have been expressed as NA total content/organ.…”

“…Conversely, the growth pattern of NA-C nerves of uterine intramural blood vessels and the uterine artery does not change at puberty or in the young adult and fully adult stages. [2][3][4]6 The total content of NA in the uterine horn and parametrial tissue does not change during puberty; however, since the weight of these uterine regions increases markedly, a fall in the concentration of NA is observed. On the other hand, in the uterine cervix there is a parallel increase between organ weight and NA content.…”

“…In this context it is important to analyze what prevents the NA-C nerves from developing in parallel with the myometrial and parametrial smooth muscle, while sensory nerves of the uterus and NA-C nerves of the cervix and blood vessels seem to develop parallel with their target smooth muscle. [2][3][4]6 Considering that the NA-C nerves of the uterus are susceptible to sex hormones 15,16,23,31 and that puberty is associated with an important endocrine reorganization, 20 it is possible that changes in the non-vascular innervation of the uterus could be related with the increase in oestrogen and progesterone occurring at puberty. In the present study, as a first approach to test the possibility that NA-C nerves are sensitive to sex hormones during development, the noradrenergic innervation of the rat uterus has been analyzed histochemically and biochemically, following acute and chronic administration of oestrogen during development.…”