Abstract
The urinary bladder is innervated by parasympathetic preganglionic neurons (PPNs) that express μ-opioid receptors (MOR) in the sacral parasympathetic nucleus (SPN) at lumbosacral segments L6-S1. The SPN also contains endomorphin 2 (EM2)-immunoreactive (IR) fibers and terminals. EM2 is the endogenous ligand of MOR. In the present study, retrograde tract-tracing with cholera toxin subunit b (CTb) or wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) via the pelvic nerve combined with immunohistochemical staining for EM2 and MOR to identify PPNs within the SPN as well as synaptic connections between the EM2-IR terminals and MOR-expressing PPNs in the SPN of the rat. After CTb was injected into the pelvic nerve, CTb retrogradely labeled neurons were almost exclusively located in the lateral part of the intermediolateral gray matter at L6-S1 of the lumbosacral spinal cord. All of the them also expressed MOR. EM2-IR terminals formed symmetric synapses with MOR-IR, WGA-HRP-labeled and WGA-HRP/MOR double-labeled neuronal cell bodies and dendrites within the SPN. These results provided morphological evidence that EM2-containing axon terminals formed symmetric synapses with MOR-expressing PPNs in the SPN. The present results also show that EM2 and MOR might be involved in both the homeostatic control and information transmission of micturition.
Highlights
The micturition reflex is an autonomic reflex that is mediated by a simple spino-bulbo-spinal pathway that passes through the pontine micturition center [1,2,3]
Previous studies have demonstrated that sacral parasympathetic preganglionic neurons (PPNs) in the sacral parasympathetic nucleus (SPN) can be assigned to 3 groups on the basis of their morphology and location [7,34]
These groups are denoted as the dorsal band (DB), lateral band (LB) and internal band (IB)
Summary
The micturition reflex is an autonomic reflex that is mediated by a simple spino-bulbo-spinal pathway that passes through the pontine micturition center [1,2,3]. Immunohistochemical studies have indicated that m-opioid receptors (MOR)-immunoreactive (-IR) neurons are widely distributed in the spinal gray matter, in the SPN [14,15,16]. These results are further supported by autoradiographic [17,18] and in situ hybridization histochemical studies [19] in the spinal cord. Functional analyses have demonstrated that in the rat spinal cord, MOR agonists, such as morphine, the exogenous ligand of MOR, are involved in the inhibition of bladder control [20,21,22]. Previous functional studies have shown that opioid peptides might inhibit the micturition reflex at the spinal level [31]
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