Visceral hyperalgesia as an important pathomechanism.

Visceral hypersensitivity and motility disorders are thought to be central factors in recurrent gastrointestinal symptoms without evidence of an organ pathologic cause. The gastrointestinal tract is highly innervated and has a large number of afferent nerve fibers and reflex circuits. The interactions between the peripheral and central nervous systems are described in the concept of “brain-gut axis.”

If symptoms such as flatulence, abdominal pain or cramps, bloating, diarrhea, or constipation occur over a period of at least 6 months, a diagnosis of functional gastrointestinal disorder can be made according to ROM IV criteria [1,2]. These symptoms of the upper and lower gastrointestinal tract, which are associated with considerable suffering for those affected, frequently overlap. The most common gastrointestinal complaints are functional dyspepsia and irritable bowel syndrome [3]. According to current knowledge, these are multifactorial diseases, although the exact etiological mechanism is not yet fully understood. The human digestive tract is a highly innervated system, with a multitude of afferent nerve fibers generating information regarding intestinal contents and regulatory processes of digestion, absorption, and immune defense [4]. These relationships are described in the gut-brain axis explanatory model (box).

Gut-brain axis (“Brain-Gut-Axis”)

The gut-brain axis is a concept for the interaction of the peripheral and central nervous systems involving neuroendocrine and neuroimmunological processes [16]. This also affects psychosocial factors (e.g. stress processing) and provides a partial explanation for the fact that psychological problems occur more frequently in patients with functional dyspepsia or irritable bowel syndrome [17]. Another pathogenetic factor, which according to recent findings is becoming increasingly important, is the microbiome and the mycobiome [7,18].

Increased vigilance for nociceptive intestinal stimuli is characteristic

The mechanism of visceral hypersensitivity refers to increased vigilance to specific sensations in the gastrointestinal tract and has long been discussed as an important pathogenetic factor for functional digestive complaints [5]. Deeper perceptual and pain thresholds to intestinal stimuli are thought to contribute to central nervous sensitization. Visceral hypersensitivity is a major nociceptive mechanism in both irritable bowel syndrome and functional dyspepsia [6]. Functional dyspepsia is characterized by epigastric pain, among other symptoms. Irritable bowel syndrome is associated with altered gastrointestinal microflora and a low pain threshold when the bowel wall expands. According to the ROM-IV consensus, after ruling out organic causes, a symptom-oriented, individualized and time-limited therapy should be implemented. The primary goal of treatment is to reduce symptoms and improve quality of life [1].

Peppermint/caraway oil combination has analgesic and antimicrobial effects

Peppermint (Mentha×piperita L.) and caraway (Carum carvi L.) are medicinal plants with a long tradition. The analgesic efficacy of peppermint oil and its relaxing effects on the muscles of the gastrointestinal tract are due to the binding of the ingredient menthol to the cold receptor (TRPM8) [8]. Caraway oil has carminative and antispasmodic effects, relieves the feeling of fullness and has antimicrobial and antioxidant properties. The growth of pathogenic germs is inhibited without exerting negative effects on desirable intestinal bacteria. ^Carmenthin® (active ingredient name: menthacarin) is a phytopharmacological preparation based on a high-dose mixture of peppermint and caraway oil. The well-tolerated drug is approved for use by health insurance companies in Switzerland for adults and adolescents aged 12 years and older for the treatment of mild cramps, bloating, epigastric pain and flatulence [9,10]. Thanks to the synergistic effect of the high-dose combination of the two essential oils, menthacarin reduces post-inflammatory visceral hyperalgesia by up to 50% in a placebo comparison [11]. Through antifungal and antibacterial properties, the phytopharmacological preparation counteracts a deep pain threshold often associated with visceral hyperalgesia.

Proven effective for functional gastrointestinal complaints

A double-blind placebo-controlled randomized multicenter trial (n=114) demonstrated the efficacy of menthacarin (2x/d 1 capsule) in patients with chronic or recurrent functional dyspepsia [12]. Relief of pain and discomfort was a major active factor. At the measurement time points 2 weeks and 4 weeks after baseline, symptom reduction was significantly greater in the treatment arm than in the placebo condition (p<0.001). There is also empirical evidence regarding irritable bowel syndrome. For example, a meta-analysis based on the evaluation of five randomized placebo-controlled human experimental studies found that peppermint oil is effective in relieving discomfort associated with irritable bowel symptoms as well as abdominal pain [13]. In the S3 guideline Irritable Bowel Syndrome of the German Society for Digestive and Metabolic Diseases there is a recommendation for Menthacarin [14]. Recent studies also address the efficacy of this phytopharmacological combination treatment. For example, in animal models, menthacarin has been shown to reduce visceral hypersensitivity [15].

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