The Involvement of the Nociceptin Receptor in the Antinociceptive Action of Nitrous Oxide

Himukashi, Shugaku; Takeshima, Hiroshi; Koyanagi, Sahoko; Shichino, Tsutomu; Fukuda, Kazuhiko

doi:10.1213/01.ane.0000230601.64098.cc

Cited by 9 publications

(5 citation statements)

References 16 publications

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“…10 High concentrations of isoflurane (1.5 MAC) depressed c-Fos expression in spinal lamina II, whereas fentanyl reduced expression in lamina V. 11 Results with nitrous oxide have been controversial. While some have reported little or no effect of nitrous oxide 44,45 or even an increase, 46 many studies, including the present one, demonstrate that nitrous oxide alone reduced dorsal horn c-Fos expression. 11,47,48 Thus, in the present work, nitrous oxide prevented c-Fos expression in superficial dorsal horn (lamina I-II).…”

Section: Discussioncontrasting

confidence: 53%

Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

et al. 2013

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Background We examined in vivo the effects of general anesthetics on evoked substance P release (primary afferent excitability) and c-Fos expression (neuronal activation) in superficial dorsal horn. Methods Rats received saline, propofol (100mg/kg), pentobarbital (50mg/kg), isoflurane (2 minimum alveolar concentration), nitrous oxide (66%) or fentanyl (30μg/kg). During anesthesia, rats received intraplantar 5% formalin (50μl) to left hindpaw. Ten min later, rats underwent transcardial perfusion with 4% paraformaldehyde. Substance P release from small primary afferents was assessed by incidence of Neurokinin 1 receptor (NK1r) internalization in the superficial dorsal horn. In separate studies, rats were sacrificed after 2 hrs and c-Fos expression measured. Results Intraplantar formalin induced robust NK1r internalization in ipsilateral dorsal horn (ipsilateral: 54±6% [mean±SEM], contralateral: 12±2%, P<0.05, n=4). Fentanyl, but not propofol, pentobarbital, isoflurane nor nitrous oxide alone inhibited NK1r internalization. However, 2 minimum alveolar concentration isoflurane + nitrous oxide reduced NK1r internalization (27±3%, P<0.05, n=5). All agents reduced c-Fos expression (control: 34±4, fentanyl: 8±2, isoflurane: 12±3, nitrous oxide: 11±2, isoflurane + nitrous oxide: 12±1, pentobarbital: 11±2, propofol: 13±3, P<0.05, n=3). Conclusion General anesthetics at anesthetic concentrations block spinal neuron activation through a mechanism which is independent of an effect upon small primary afferent peptide release. The effect of fentanyl alone and the synergistic effect of isoflurane and nitrous oxide on substance P release suggests a correlative rationale for the therapeutic use of these anesthetic protocol by blocking nociceptive afferent transmitter release and preventing the initiation of cascade which are immediately postsynaptic to the primary afferent.

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Section: Discussioncontrasting

confidence: 53%

Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

et al. 2013

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“…Nociceptin has a potent antinociceptive effect in the abdomen, as shown in the acetic acid-induced abdominal pain model in mice (Himukashi et al, 2006). This suggests that the activation of NOP receptors is crucial for abdominal nociceptive signaling and that the NOP ligands may alleviate GI tract-related pain (Himukashi et al, 2006). Recently, Agostini et al (2009) confirmed the antinociceptive action of nociceptin, characterized by the changes in the visceromotor response to colorectal distension in the rat model of TNBS-induced colitis.…”

Section: Discussionmentioning

confidence: 95%

“…There are two types of abdominal pain: somatic, which is musculoskeletal; and visceral, caused by stretching of the viscera by obstruction or widely affected inflammation. Nociceptin has a potent antinociceptive effect in the abdomen, as shown in the acetic acid-induced abdominal pain model in mice (Himukashi et al, 2006). This suggests that the activation of NOP receptors is crucial for abdominal nociceptive signaling and that the NOP ligands may alleviate GI tract-related pain (Himukashi et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory and Antinociceptive Action of an Orally Available Nociceptin Receptor Agonist SCH 221510 in a Mouse Model of Inflammatory Bowel Diseases

Sobczak

Mokrowiecka

Cygankiewicz

et al. 2013

J Pharmacol Exp Ther

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The nociceptin receptors (NOPs) are expressed in the gastrointestinal (GI) tract on muscle cell membranes and neurons, as well as the immune cells that infiltrate the mucosa. The involvement of NOPs in the pathophysiology of GI inflammation has been suggested, but due to the lack of selective NOP agonists, it never fully elucidated. Our aim was to characterize the anti-inflammatory and antinociceptive effect of the NOP agonist, SCH 221510 [3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo [3.2.1]octan-3-ol], as a potential therapeutic strategy in the treatment of inflammatory bowel diseases (IBD). The anti-inflammatory action of SCH 221510 was determined after intraperitoneal, oral, and intracolonic administration of SCH 221510 (0.1-3.0 mg/kg once or twice daily) in mice treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Antinociceptive action of SCH 221510 was evaluated in the mouse model of mustard oil (MO)-induced abdominal pain. Relative NOP mRNA expression was assessed in patients with IBD using real-time reverse transcriptase-polymerase chain reaction. We found that the expression of NOP mRNA was significantly decreased in patients with IBD. The administration (0.1 and 1.0 mg/kg i.p. twice daily and 3 mg/kg p.o. twice daily) of SCH 221510 attenuated TNBS colitis in mice. This effect was blocked by a selective NOP antagonist [J-113397 [(6. The intracolonic injections of SCH 221510 did not improve colitis in mice. The antinociceptive effect of SCH 221510 was observed after oral administration of SCH 221510 in MO-induced pain tests in mice with acute colitis. In conclusion, our results show a potent anti-inflammatory and antinociceptive effect upon selective activation of NOP receptors and suggest that the NOP agonist SCH 221510 is a promising drug candidate for future treatment of IBD.

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“…N/OFQ and NOP are widely expressed in the central nervous system [7,8] and have been shown to be involved in the modulation of nociceptive signals. Although we previously reported that the analgesic effect of N 2 O was markedly smaller in NOP-defi cient mice than in wild-type mice [9], it is not known whether NOP antagonists affect N 2 Oinduced analgesia. The aim of the present work was to investigate the effect of a NOP antagonist, JTC-801, on of baseline TFL, each mouse was exposed to the mixed gas for 30 min, and then transferred outside the chamber to determine the post-treatment TFL.…”

Section: Abstract Nitrous Oxide · Analgesia · Nociceptinmentioning

confidence: 92%

Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice

Koyama

Fukuda

2009

J Anesth

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The mechanism of the analgesic effect of nitrous oxide (N(2)O) has not been completely clarified. Although we have reported that the analgesic effect of N(2)O was significantly decreased in nociceptin-orphanin FQ (N/OFQ) receptor (NOP)-deficient mice, the effect of nociceptin receptor antagonists on N(2)O-induced analgesia has not been reported. In this investigation, we examined the effect of the NOP antagonist JTC-801 on N(2)O-induced analgesia in 129Sv mice by the writhing test and tail flick test, and demonstrated that the analgesic effect of N(2)O was suppressed by the intraperitoneal administration of JTC-801.

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The Involvement of the Nociceptin Receptor in the Antinociceptive Action of Nitrous Oxide

Cited by 9 publications

References 16 publications

Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

Effects of General Anesthetics on Substance P Release and c-Fos Expression in the Spinal Dorsal Horn

Anti-Inflammatory and Antinociceptive Action of an Orally Available Nociceptin Receptor Agonist SCH 221510 in a Mouse Model of Inflammatory Bowel Diseases

Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice

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