Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders
Abstract
1. Introduction
2. Neurophysiology of Visceral Pain
2.1. CNS Modulation of Visceral Pain
2.2. Vagal Innervation
2.3. Thoracolumbar Innervation
2.4. Pelvic Innervation
2.5. ENS Reflexes
3. Chronic Visceral Pain: The Paradigms of IBS and IBD
4. Chronic Abdominal Visceral Pain: Focus on Marine Toxins as Possible Therapeutic Tools
4.1. Toxins Active at VGSCs
4.1.1. VGSCs
4.1.2. Tetrodotoxin and Saxitoxin
4.2. Toxins Active at VGCC
4.2.1. VGCCs
4.2.2. ω-Conotoxin
4.2.3. α-Conotoxin
4.3. Toxins Active at TRPs
4.4. Toxins Acting at ASICs
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound/Target | Dose/Concentration (Administration route) | Model | Parameter Evaluated | Effect | REF |
---|---|---|---|---|---|
TTX/Nav | 1, 3, 6 g/kg (s.c.) | Intracolonic instillation of capsaicin in WT (C57BL/6 background) and Nav 1.7 conditional KO | -Pain-related behaviors (licking of the abdomen, stretching of abdomen, abdominal retractions); -Referred mechanical hyperalgesia (response to abdominal stimulation with von Frey electrodes) | -Similar dose-dependent reduction in WT and KO -Similar dose-dependent reduction in WT and KO | [55] |
3, 6 g/kg (s.c.) | Intracolonic instillation of mustard oil in WT and Nav 1.7 conditional KO mice | Pain-related behaviors (licking of the abdomen, stretching of abdomen, abdominal retractions) | Dose-dependent reduction, similar in WT and KO | [55] | |
0.3, 1, 3, 6 g/kg (s.c.) | Intraperitoneal acetic-acid induced writhing test in Swiss Webster mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Dose-dependent reduction | [56] | |
ω-conotoxin MVIIA/Cav 2.2 | 1, 10, 30, 100 pmol/site (i.t.) | Intraperitoneal acetic-acid induced writhing test in Swiss mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Dose-dependent reduction | [57] |
1, 10, 30, 100 pmol/site (i.t.) | Intracolonic instillation of capsaicin in Swiss mice | Pain-related behaviors (licking of the abdomen, stretching of abdomen, abdominal retractions). | Dose-dependent reduction | [57] | |
30 pmol/site (i.t.) | Intraperitoneal acetic-acid induced writhing test in Swiss mice | Measurement of glutamate levels in the CSF | Reduction of nociceptive stimulus-induced increase of glutamate levels in the CSF | [57] | |
30 pmol/site (i.t.) | Intracolonic instillation of capsaicin in Swiss mice | Measurement of glutamate levels in the CSF | Reduction of nociceptive stimulus-induced increase of glutamate levels in the CSF | [57] | |
Vc1.1/GABAB | 1 M (in vitro) | Human thoracolumbar DRG | Whole-cell patch clamp recordings | Inhibition of a selective population of DRG neurons | [58] |
1, 10, 100, 1000 nM (in vitro) | CVH mouse model induced by intrarectal TNBS administration | Ex vivo single fiber recordings of primary afferents splanchnic colonic and pelvic colorectum afferents | Concentration-dependent inhibition of mechanosensitivity (the effect was higher in CVH animals) | [58] | |
1, 10, 100, 1000 nM (in vitro) | CVH mouse model induced by intrarectal TNBS administration | Ex vivo single fiber recordings of splanchnic colonic primary afferents. | Concentration-dependent inhibition of mechanosensitivity (the effect was higher in CVH animals) | [59] | |
10 nM (in vitro) | CVH mouse model induced by intrarectal TNBS administration | Whole-cell patch clamp recordings on colonic extrinsic primary afferents | Significant inhibition of the excitability of colonic control DRG which was higher in CVH animals | [59] | |
1 M (intrarectal enema) | CVH mouse model induced by intrarectal TNBS administration followed by noxious distension of the colorectum | VMR to colorectal distension by electromyography assessment | Significant reduction of VMR in CVH mice to noxious distension pressures | [60] | |
[Ser3] Vc1.1(1-8)/GABAB | 100 pM, 30 nM, 1 M (in vitro) | Mouse DRG | Whole-cell patch clamp recordings | Inhibition of VGCC | [61] |
1, 10, 100 and 1000 nM (ex vivo, applied on the colonic surface) | CVH mouse model induced by intrarectal TNBS administration | In vitro single-unit extracellular recordings of action potential discharge from splanchnic colonic afferents. | Concentration-dependent inhibition of mechanosensitivity of splanchnic colonic primary afferents | [61] | |
1 M (intrarectal enema) | Noxious distension of the mouse colorectum | VMR to colorectal distension by electromyography assessment | Significant reduction of VMR to colorectal distension vs vehicle treated animals | [61] | |
APCH1/TRPV1 | 0.5 mg/kg (i.v.) | Intraperitoneal acetic-acid induced writhing test in CD1 mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Reduction | [62] |
APCH3/TRPV1 | 0.1, 0.5 mg/kg (i.v.) | Intraperitoneal acetic-acid induced writhing test in CD1 mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Reduction | [62] |
APETx2/ASIC3 | 25 g/kg | Acute gastric mucosal damage induced by WIRS in Wistar rats | -intragastric pH -gastric histopathological changes -UI -ASIC3 expression in thoracic DRG neurons projecting to the stomach | Significant reduction of WIRS-induced: -gastric mucosal injury, UI score, gastric acidity -ASIC3 expression in DRG | [63] |
0.002, 0.02, 0.2, 1 mg/kg (i.m.) | Intraperitoneal acetic-acid induced writhing test in CD1 mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Bell-shaped reduction of abdominal contractile responses | [64] | |
Ugr9-1/ASIC3 | −0.002, 0.02, 0.2, 1 mg/kg (i.m.); −0.5, 0.1, 0.01 mg/kg (i.v.) | Intraperitoneal acetic-acid induced writhing test in CD1 mice | Number of complete abdominal contractions accompanied with stretching of hind limbs | Dose-dependent reduction of abdominal contractile responses | [64,65] |
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Baj, A.; Bistoletti, M.; Bosi, A.; Moro, E.; Giaroni, C.; Crema, F. Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders. Toxins 2019, 11, 449. https://doi.org/10.3390/toxins11080449
Baj A, Bistoletti M, Bosi A, Moro E, Giaroni C, Crema F. Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders. Toxins. 2019; 11(8):449. https://doi.org/10.3390/toxins11080449
Chicago/Turabian StyleBaj, Andreina, Michela Bistoletti, Annalisa Bosi, Elisabetta Moro, Cristina Giaroni, and Francesca Crema. 2019. "Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders" Toxins 11, no. 8: 449. https://doi.org/10.3390/toxins11080449
APA StyleBaj, A., Bistoletti, M., Bosi, A., Moro, E., Giaroni, C., & Crema, F. (2019). Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders. Toxins, 11(8), 449. https://doi.org/10.3390/toxins11080449