Supraspinal Mechanisms of Intestinal Hypersensitivity

Lyubashina, O. A.; Sivachenko, Ivan B.; Panteleev, S. S.

doi:10.1007/s10571-020-00967-3

Cited by 16 publications

(9 citation statements)

References 231 publications

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“…However, the analgesic advantage of nalbuphine did not last for more than 8 h after surgery, regardless of whether a single dose or its action ranges no more than 8 h. A possible explanation is that the pain elicited by this type of minimally invasive surgery was too low to yield a significant difference in pain scores at 48 h after surgery [26]. It is interesting that in our subgroup analyses, we found that patients with a history of symptomatic gallbladder [27], which are related to potentiation of hypersensitivity and hyperalgesia [28]. The results were unexpected; to the best of our knowledge, there is no report about the effect of nalbuphine on visceral hyperalgesia, although we have reported that nalbuphine can improve remifentanil-induced hyperalgesia (RIH) [29].…”

Section: Confidence Intervalmentioning

confidence: 74%

“…Prolonged symptomatic gallbladder disease presents a chronic condition caused by continuous inflammation. The inflammation-induced hyperexcitability of extrinsic visceral afferents is associated with nociceptive and opioid receptors [ 27 ], which are related to potentiation of hypersensitivity and hyperalgesia [ 28 ]. The results were unexpected; to the best of our knowledge, there is no report about the effect of nalbuphine on visceral hyperalgesia, although we have reported that nalbuphine can improve remifentanil-induced hyperalgesia (RIH) [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Liu¹,

Hu²,

Hu³

et al. 2021

Pain Ther

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Introduction: Post-operative visceral pain is common in early postoperative period after laparoscopic surgery. As a kappa opioid receptor agonist, the antinociceptive effects of nalbuphine in visceral pain are consistent across a multitude of experimental conditions irrespective of species. We hypothesized that preemptive nalbuphine can decrease the visceral pain for patients with incisional infiltration of ropivacaine after laparoscopic cholecystectomy. Methods: In a multicenter, prospective, doubleblind, placebo-controlled, randomized clinical trial, 2094 participants scheduled for laparoscopic cholecystectomy were randomly assigned to receive nalbuphine (Nal group, n = 1029) or placebo (Con group, n = 1027). The Nal group received intravenous nalbuphine 0.2 mgÁkg -1 and the Con group received saline in a similar way. The primary endpoint was the effect of nalbuphine on post-operative visceral pain intensity scores within 24 h postoperatively. The total amount of analgesic as well as complications were recorded. Results: A total of 1934 participants were analyzed. Nalbuphine reduced the visceral pain both at rest (b = -0.1189, 95% CI -0.23 to -0.01, P = 0.037) and movement (b = -0.1076, 95% CI -0.21 to -0.01, P = 0.040) compared with placebo. Patients in the Nal group required less frequent supplemental analgesic administration during the first 24 h after surgery. There were fewer patients in the Nal group who experienced nausea and vomiting (PONV) (P = 0.008). Conclusions: Preemptive nalbuphine administered at a dose of 0.2 mgÁkg -1 was safe and effective at reducing the postoperative visceral pain and supplemental analgesic use in patients undergoing laparoscopic cholecystectomy.

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Section: Confidence Intervalmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Liu¹,

Hu²,

Hu³

et al. 2021

Pain Ther

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“…However, studies in animal post-inflammation models indicated that visceral hypersensitivity to mechanical or chemical stimuli persists after the inflammation has resolved (Coldwell JR et al,2007;Lyubashina et al,2022), and it inspired us to explore where the "memory" of the visceral afferent hyperexcitability is stored. Hippocampus is a key structure for cognition and memory.…”

mentioning

confidence: 99%

“…In addition, the disorders responses to the interoceptive signaling can induce clinically relevant phenotypes, including chronic visceral hypersensitivity (Labrenz et al,2022). At the same time, adverse life events, stress, and anxiety/depression can aggravate the degree of abdominal pain (Lyubashina et al,2022).…”

mentioning

confidence: 99%

Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway

et al. 2022

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The goal of the study was to analyze whether WJP can alleviate visceral hypersensitivity in IBS-D model rats. In this study, 36 Sprague–Dawley (SD) rats aged 4 weeks old were randomly divided into two groups: the model group (n = 27) and the control group (n = 9). The rat model of IBS-D was established by modified compound methods for 4 weeks. After the modification, IBS-D rats were randomly divided into three groups, namely, the IBS-D model group (n = 9), the positive drug group (n = 9), and the WJP group (n = 9), with different interventions, respectively. The control group was fed and allowed to drink water routinely. The Bristol stool scale scores were used to assess the severity of diarrhea. Abdominal withdrawal reflex (AWR) scores were used to assess visceral sensitivity. Expression of TNF-α was measured, and histopathological examinations were performed to assess colon inflammation in IBS-D model rats. Key factors of the MEK/ERK signal pathway in the tissue of the colon and hippocampus were measured to analyze the mechanism of WJP. Compared with the control group, the Bristol stool scale scores in the model group were significantly increased (p < 0.0001). The scores of the WJP group were significantly decreased compared with the model group (p = 0.0001). Compared with the control group, AWR scores in the model group at each pressure level were significantly increased (p = 0.0003, p < 0.0001, p = 0.0007, and p = 0.0009). AWR scores of the WJP group were significantly decreased compared with the model group (p = 0.0003, p = 0.0007, p = 0.0007, and p = 0.0009). Compared with the control group, the model group had significantly higher expression of TNF-α in the colon tissue (p < 0.0001). However, the WJP group had significantly lower level of TNF-α compared with the model group (p < 0.0001). Meanwhile, compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue was significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the colon tissue were significantly decreased in the WJP group (p < 0.0001, p = 0.0019, and p = 0.0013). Compared with the control group, the relative expression of the proteins of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue were significantly increased in the model group (p < 0.0001). Compared with the model group, the relative expression of the proteins in the hippocampus tissue were significantly decreased in the WJP group (p = 0.0126, p = 0.0291, and p = 0.0145). The results indicated that WJP can alleviate visceral hypersensitivity in IBS-D model rats, possibly mediated by downregulating the expression of TNF-α, p-MEK1/2, p-ERK1, and p-ERK2 in the colon tissue. At the same time, WJP also affects downregulating the expression of p-MEK1/2, p-ERK1, and p-ERK2 in the hippocampus tissue.

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“…We found that this optical stimulation, at both 30 Hz (Figure 4F) and 15 Hz (Figure S11E), was sufficient to drive robust aversive learning in DSS-treated Vglut3 Cdx2 -Catch mice, requiring only 3-5 trials to produce conditioned avoidance, whereas the same optical stimulation produced minimal aversive learning in control littermates that lacked CatCh expression (Figure 4F). Without DSS treatment, optical stimulation produced a trend of aversive learning, almost reaching significance after six trials (Figure S11F), indicating the occurrence of sensitized information transmission from the VGLUT3 Cdx2 -CatCh + terminals to the PBcil in mice with colitis, although sensitization could occur in more down downstream targets such as the ACC and the amygdala associated with aversive learning (Louwies et al, 2021; Lyubashina et al, 2022; Prusator and Greenwood-Van Meerveld, 2017; Thompson and Neugebauer, 2017, 2019; Wang et al, 2017; Yan et al, 2012). Importantly, this optical stimulation was insufficient to induce VMRs in DSS-treated Vglut3 Cdx2 -Catch mice (Figure S11G).…”

Section: Resultsmentioning

confidence: 99%

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

Lin

2022

Preprint

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Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here we used a focal colorectal distention (fCRD) method to drive visceromotor responses (VMRs) plus affective pain-indicative aversive learning. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion. We next showed that spinal VGLUT3 neurons mediate affective visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons are dispensable for driving VMRs. Anatomically, VGLUT3 neurons send projection to the parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information.

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Supraspinal Mechanisms of Intestinal Hypersensitivity

Cited by 16 publications

References 231 publications

Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Wenshen-Jianpi prescription, a Chinese herbal medicine, improves visceral hypersensitivity in a rat model of IBS-D by regulating the MEK/ERK signal pathway

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

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