Abstract
Substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), play important roles in transmitting and regulating somatosensory nociceptive information. However, their roles in visceral nociceptive transmission and regulation remain to be elucidated. In the previous study, moderate SP immunoreactive (SP-ir) terminals and NK1R-ir neurons were observed in the dorsal commissural nucleus (DCN) of the lumbosacral spinal cord. Thus we hypothesized that the SP-NK1R system is involved in visceral pain transmission and control within the DCN. The acute visceral pain behaviors, the colon histological changes and the temporal and spatial changes of NK1R-ir structures and Fos expression in the neurons of the DCN were observed in rats following lower colon instillation with 5% formalin. The formalin instillation induced significant acute colitis as revealed by the histological changes in the colon. NK1R internalization in the DCN was obvious at 8 min. It reached a peak (75.3%) at 30 min, began to decrease at 90 min (58.1%) and finally reached the minimum (19.7%) at 3 h after instillation. Meanwhile, formalin instillation induced a biphasic visceral pain response as well as a strong expression of Fos protein in the nuclei of neurons in the DCN. Finally, intrathecal treatment with the NK1R antagonist L732138 attenuated the NK1R internalization, Fos expression and visceral nociceptive responses. The present results suggest that the visceral nociceptive information arising from inflamed pelvic organs, such as the lower colon, might be mediated by the NK1R-ir neurons in the DCN of the lumbosacral spinal cord.
Highlights
Visceral pain occurs after mechanical or chemical stimulation in and around the internal organs
We found that pretreatment with L732138 prior to formalin instillation can significantly reduce the number of Fos immunoreactive (Fos-ir) neurons at 30 min after stimuli to approximately 50% less than the formalin instillation group (1363, per section; P,0.001 L732138 pretreatment vs. saline pretreatment or L732138 post treatment or formalin instillation group)
We used an acute colitis model to systemically analyze the spatial and temporal changes of neurokinin 1 receptor (NK1R) and Fos in dorsal commissural nucleus (DCN) neurons, which made detailed positioning of pelvic visceral primary sensitive neurons in spinal cord based on previous study [21,22]
Summary
Visceral pain occurs after mechanical or chemical stimulation in and around the internal organs. In contrast to somatic pain, visceral pain is difficult to localize and is often described as ‘‘deep pressure,’’ ‘‘cramping,’’ ‘‘spasms’’ or ‘‘squeezing’’. The study of visceral pain is far behind that of somatic pain because it is difficult to access internal organs [1,2] and the pathway of visceral noxious information transmission is complicated and remains largely unrevealed by current research techniques [3,4]. The biological actions of SP are mediated via the neurokinin 1 receptor (NK1R), which belongs to the G-protein-coupled receptor (GPCR) family. Previous studies have shown that SP and NK1R are involved in the transmission of nociceptive information and the modulation of nociceptive pathways in the spinal cord [6,7]
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