Acute Colitis Induces Neurokinin 1 Receptor Internalization in the Rat Lumbosacral Spinal Cord

Zhang, Ming Ming; Ji, Wei; Li, Pei; Wang, Wen; Chen, Tao; Wang, Wei; Li, Hui; Zhang, Ting; Wu, Sheng Xi; Li, Yun Qing

doi:10.1371/journal.pone.0059234

Cited by 13 publications

(19 citation statements)

References 45 publications

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“…Subsequently, a polyethylene tube, which was wrapped in surgical tape at ~30 mm from the edge, was inserted through the anus. A 5% formalin solution or saline (100 µl) was injected through the tube slowly to prevent leakage (15).…”

Section: Animalsmentioning

confidence: 99%

Involvement of neurokinin 1 receptor within the cerebrospinal fluid-contacting nucleus in visceral pain

Zhang

Liu

Wang

et al. 2017

Molecular Medicine Reports

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Studies have shown that the cerebrospinal fluid-contacting nucleus (CSF-CN) may be associated with the transduction and regulation of pain signals. However, the role of the CSF-CN remains to be elucidated. Emerging evidence has suggested that neurokinin 1 receptor (NK1R) is important in the development of visceral pain and hyperalgesia, however, whether NK1R exists in the CSF-CN and its exact role in visceral pain remain to be fully elucidated. In the present study, double-labeled immunofluorescence staining and western blot analysis were performed to investigate this. It was revealed that NK1R was distributed in the CSF-CN. Following the induction of visceral pain by formalin instillation, NK1R in the CSF-CN was upregulated. In addition, by observing the behaviors of rats subjected to visceral pain, it was found that visceral pain was relieved by lateral intracerbroventricular injection of the NK1R antagonist, RP67580. These data provided a broader understanding of the role of NK1R in the CSF-CN and demonstrated that the CSF-CN was involved in acute visceral pain via the regulation of NK1R.

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Section: Animalsmentioning

confidence: 99%

Involvement of neurokinin 1 receptor within the cerebrospinal fluid-contacting nucleus in visceral pain

Zhang

Liu

Wang

et al. 2017

Molecular Medicine Reports

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“…We validated this method by comparing it to conventional immunoassay measures of substance P release and found that it has higher sensitivity (Marvizon et al, 2003a). In addition, NK1R internalization can be measured non-invasively in vivo (Mantyh et al, 1995, Allen et al, 1997, Honore et al, 1999, Kondo et al, 2005, Adelson et al, 2009, Zhang et al, 2010b), allows the spatial location of substance P release (Abbadie et al, 1997, Allen et al, 1999, Hughes et al, 2007, Zhang et al, 2013) and measures substance P release at physiologically relevant concentrations that activate the NK1R (Trafton et al, 1999). NK1R internalization may also detect the release of neurokinin A, but not the release of neurokinin B.…”

mentioning

confidence: 99%

“…Although multiple studies have investigated substance P release in inflammatory conditions (Abbadie et al, 1997, Allen et al, 1999, Honore et al, 1999, Honore et al, 2002, Zhang et al, 2013), just a few of them have investigated how it is affected by nerve injury. These studies have centered primarily on the type of primary afferents (i.e., Aβ-, Aδ-of C-fibers) that release substance P after nerve injury (Allen et al, 1999, Malcangio et al, 2000, Hughes et al, 2007) and have not investigated changes in the pharmacological modulation of substance P release.…”

mentioning

confidence: 99%

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

2014

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Opiate analgesia in the spinal cord is impaired during neuropathic pain. We hypothesized that this is caused by a decrease in μ-opioid receptor inhibition of neurotransmitter release from primary afferents. To investigate this possibility, we measured substance P release in the spinal dorsal horn as neurokinin 1 receptor (NK1R) internalization in rats with chronic constriction injury (CCI) of the sciatic nerve. Noxious stimulation of the paw with CCI produced inconsistent NK1R internalization, suggesting that transmission of nociceptive signals by the injured nerve was variably impaired after CCI. This idea was supported by the fact that CCI produced only small changes in the ability of exogenous substance P to induce NK1R internalization or in the release of substance P evoked centrally from site of nerve injury. In subsequent experiments, NK1R internalization was induced in spinal cord slices by stimulating the dorsal root ipsilateral to CCI. We observed a complete loss of the inhibition of substance P release by the μ-opioid receptor agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) in CCI rats but not in sham-operated rats. In contrast, DAMGO still inhibited substance P release after inflammation of the hind paw with complete Freund’s adjuvant and in naïve rats. This loss of inhibition was not due to μ-opioid receptor downregulation in primary afferents, because their colocalization with substance P was unchanged, both in dorsal root ganglion neurons and primary afferent fibers in the dorsal horn. In conclusion, nerve injury eliminates the inhibition of substance P release by μ-opioid receptors, probably by hindering their signaling mechanisms.

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“…, 50 μg, 10 min before SP injection; 81.62 ± 2.86%, F = 1.201, P = 0.828; Figure 7C) but was decreased by L732138 ( i.t. , 100 nM, 10 min before SP injection; Cahill and Coderre, 2002; Zhang et al, 2013; Figure 7D). These results indicated that EM2 had no direct effects on NK1R internalization.…”

Section: Resultsmentioning

confidence: 94%

“…In lamina I of the SDH, the NK1R-positive neurons that included the nucleus and a large area of cytoplasm were selected. NK1R-positive neurons with 10 or more endosomes in the soma were considered as internalized neurons (Zhang et al, 2013). The ability of NK1R internalization was represented as the proportion of NK1R-internalized cells (NK1R-internalized cells/NK1R-positive cells).…”

Section: Methodsmentioning

confidence: 99%

Endomorphin-2 Inhibition of Substance P Signaling within Lamina I of the Spinal Cord Is Impaired in Diabetic Neuropathic Pain Rats

Wan

Bai

Kou

et al. 2017

Front. Mol. Neurosci.

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Opiate analgesia in the spinal cord is impaired in diabetic neuropathic pain (DNP), but until now the reason is unknown. We hypothesized that it resulted from a decreased inhibition of substance P (SP) signaling within the dorsal horn of the spinal cord. To investigate this possibility, we evaluated the effects of endomorphin-2 (EM2), an endogenous ligand of the μ-opioid receptor (MOR), on SP release within lamina I of the spinal dorsal horn (SDH) in rats with DNP. We established the DNP rat model and compared the analgesic efficacy of EM2 between inflammation pain and DNP rat models. Behavioral results suggested that the analgesic efficacy of EM2 was compromised in the condition of painful diabetic neuropathy. Then, we measured presynaptic SP release induced by different stimulating modalities via neurokinin-1 receptor (NK1R) internalization. Although there was no significant change in basal and evoked SP release between control and DNP rats, EM2 failed to inhibit SP release by noxious mechanical and thermal stimuli in DNP but not in control and inflammation pain model. We also observed that EM2 decreased the number of FOS-positive neurons within lamina I of the SDH but did not change the amount of FOS/NK1R double-labeled neurons. Finally, we identified a remarkable decrease in MORs within the primary afferent fibers and dorsal root ganglion (DRG) neurons by Western blot (WB) and immunohistochemistry (IHC). Taken together, these data suggest that reduced presynaptic MOR expression might account for the loss of the inhibitory effect of EM2 on SP signaling, which might be one of the neurobiological foundations for decreased opioid efficacy in the treatment of DNP.

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Acute Colitis Induces Neurokinin 1 Receptor Internalization in the Rat Lumbosacral Spinal Cord

Cited by 13 publications

References 45 publications

Involvement of neurokinin 1 receptor within the cerebrospinal fluid-contacting nucleus in visceral pain

Involvement of neurokinin 1 receptor within the cerebrospinal fluid-contacting nucleus in visceral pain

μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain

Endomorphin-2 Inhibition of Substance P Signaling within Lamina I of the Spinal Cord Is Impaired in Diabetic Neuropathic Pain Rats

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