Visceral hypersensitivity, including hyperalgesia, is closely related to irritable bowel syndrome. To investigate short- and long-term treatment effects of a proprietary combination of peppermint and caraway oil on electrophysiological markers of intestinal pain sensitivity, Omoloye et al. conducted a study in a rat model. Menthacarin was shown to modulate visceral hypersensitivity.
The use of peppermint and caraway oil to relieve gastrointestinal complaints has a long tradition [1]. Menthacarin refers to a proprietary combination of peppermint oil (90 mg WS® 1340) and caraway oil (50 mg WS® 1520), which has been shown to contribute to pain reduction, spasmolysis and general symptom relief in irritable bowel syndrome (IBS ) [2,3]. This has been shown in various non-clinical and clinical studies [4]. To find out more about the specific effects of menthacarin on visceral pain responses, Omoloye et al. conducted an animal study in anesthetized rats under normal and hyperalgesic conditions [4]. Hyperalgesia was induced by the administration of corticosteroids.
Colorectal distension as a model for visceral hypersensitivity
Corticosteroids or menthacarin or a combination were administered orally to the laboratory rats diluted in a sucrose solution (10%) once daily at a dose of 8 or 60 mg kg-1 (3 mL kg-1) [4]. The control group received a vehicle solution of 10% sucrose. The last administration took place at least 6 hours before the start of the CRD protocol – an experimental method to induce visceral reflexes. Colorectal distension (CRD) was induced via a 5 cm long balloon inserted through the anal canal of the anaesthetized animal, which was inflated with air at a pressure between 15 and 75 mmHg. The anterior cingulate cortex (ACC) plays a crucial role in the processing of visceral pain. Nociceptive signals elicited by CRD alter the neuronal activity of ACC neurons in anesthetized rats. Therefore, neurons from the ACC were recorded and tested for CRD. A neuron was considered responsive to CRD if its spike firing rate increased or decreased by at least 15% compared to baseline activity before CRD treatment and if this was observed for at least two CRD applications. At the end of the experiments, the animals were euthanized.
| Patients with irritable bowel syndrome (IBS ) usually suffer from persistent abdominal pain in combination with disturbed bowel function. There are three predominant subtypes: Diarrhea (IBS-D), constipation (IBS-C) or mixed forms (IBS-M). Imaging findings indicate that IBS patients show higher metabolic activity and functional differences in the anterior cingulate cortex (ACC) in response to visceral pain stimuli compared to control subjects. Furthermore, IBS is often associated with visceral hypersensitivity and hyperalgesia, so that even normal visceral physiological stimuli are perceived as discomfort and pain. |
| to [4,5] |
Important results at a glance
That chronic administration of corticosterone (8 mg kg-1) day-1 for 14 days (6 animals tested) resulted in a significant 53% increase in the net CRD response in otherwise untreated animals (p<0.001**) indicates the successful induction of visceral hyperalgesia. In contrast, in animals treated simultaneously with menthacarin (n=5) and corticosterone, the neuronal excitatory response to colorectal distension (50 s, 50 mmHg) was not enhanced. This suggests that menthacarin apparently prevented or counteracted the hyperalgesic effect of corticosterone on CRD.
** Newman-Keuls test after significant ANOVA (F2,115 = 13.4; p<0.0001)
Regarding functional differences in the ACC, 233 neurons were recorded and tested for CRD. One-week administration of menthacarin (60 mg kg-1/day; 3 animals tested) did not significantly alter the net electrophysiological response to CRD (7.1 ± 7.5 additional spikes/10 s, n=22). In contrast, long-term administration of menthacarin (60 mg kg-1) day-1 for 2 weeks (5 animals tested) resulted in a small but significantly lower net excitatory CRD response (4.8 ± 4.5 additional spikes/10 s, n=32) compared to controls (p<0.05$). This reduction was accompanied by a decrease in the proportion of cells that responded with neuronal activation in the menthacarin long-term treatment group (12.5% vs. 21% in the control group), although this difference was not statistically significant (p=0.08, chi-square test).
$ Newman-Keuls test, after significant one-way ANOVA (F2,100 = 3.2, p<0.04)
| Summary The study by Omoloye et al. showed in two animal models of visceral hyperalgesia and hypersensitivity that prolonged administration of menthacarin at clinically relevant doses attenuated colorectal distension (CRD)-induced neuronal discharges of the ACC. This indicates a protective effect with regard to visceral hypersensitivity. Although the mechanisms involved in this analgesic effect remain to be elucidated, it can be inferred that menthacarin has the therapeutic potential to attenuate visceral pain perception in the context of visceral hypersensitivity often associated with IBS. |
| according to [4] |
Literature:
- Rich G, et al: A randomized placebo-controlled trial on the effects of menthacarin, a proprietary peppermint- and caraway-oil-preparation, on symptoms and quality of life in patients with functional dyspepsia. Neurogastroenterol Motil 2017; 29(11): e13132.
- “Peppermint oil/caraway oil”, www.pharmawiki.ch,(last accessed 19.08.2024)
- Madisch A, et al: Effectiveness of menthacarin on symptoms of irritable bowel syndrome. Vienna Med Wochenschr 2019; 169(5-6): 149-155.
- Omoloye A, et al: Menthacarin treatment attenuates nociception in models of visceral hypersensitivity. Neurogastroenterol Motil 2024 Apr; 36(4): e14760.
- Zhou Q, Verne GN: New insights into visceral hypersensitivity – clinical implications in IBS. Nat Rev Gastroenterol Hepatol 2011; 8(6): 349-355.
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