Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Abstract

The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors: Studies on pregnant rat uteri in vitro

“…We found that in the presence of rolipram the forskolinstimulated cAMP accumulation was higher in the uteri of LPS-treated rats than in those of intact rats. The sensitization of adenylyl cyclase in inflammation was reported recently by our group (Klukovits et al 2004), corresponding to earlier findings of Osawa et al (2007).…”

“…On days 20 and 22 of pregnancy the rats were killed by CO 2 inhalation in the early afternoon hours, and the uteri were removed and prepared for the in vitro contractility assay, as it was reported previously (Klukovits et al 2004). Briefly, the isolated uterine horns were immediately placed in an organ bath (de Jongh solution; containing in mM: 137 NaCl, 3 KCl, 1 CaCl 2 , 1 MgCl 2 , 12 NaHCO 3 , 4 Na 2 HPO 4 , 6 glucose; pH 7.4) perfused with 95% oxygen and 5% carbon dioxide; they were trimmed of fat and the foeto-placental units were removed.…”

Modulation of Noradrenergic Neurotransmission in Isolated Rat Radial Artery

“…This could indirectly suggest the release of relaxing transmitters from local sensory nerve endings. Although the identity of the sensory mediators involved remains to be determined, we suggest that sensory nerve activation could attenuate the adrenergic contractility of the radial artery (45).…”

Nociceptin Inhibits Uterine Contractions in Term-Pregnant Rats by Signaling Through Multiple Pathways1

“…Several previous findings have confirmed that such endogenous oligo-and polypeptides (e.g., oxytocin [14]; tachykinin, previously called substance P [15,16]; and CALCA, previously called calcitonin gene-related peptide [17][18][19]) have pronociceptive and also potent modulatory effects on the uterine contractility. Investigation of the actions of these neuropeptides can provide substantial new information relating to the mediation of uterine contractions at term, either physiological or pathological.…”