Often, abdominal pain occurs in Irritable Bowel Syndrome (IBS). This is because the sensory nerves from the gut are hypersensitive to mechanical stimulation. Peppermint produces a cooling sensation and is known to provide relief from symptoms of IBS. The current study that was conducted on mice found that icilin, a cooling agent, reduced the sensitivity of the sensory nerve fibers from the gut. This might explain the mechanism by which peppermint and certain herbal remedies help to reduce abdominal pain. Drugs that modify the presence and activity of the transient receptor potential ion channel melastatin subtype 8 (TRPM8) channels in the gut wall may facilitate ushering new therapies for treating IBS in the future.
One of the prominent symptoms of IBS is abdominal pain, caused due to distension of the gut. Colon, which is a part of the gut, becomes sensitive to mechanical pressure. The pain is caused by the nerves connecting the colon and spinal column. Administration of peppermint reduces the severity of the abdominal pain in patients with IBS, but the exact mechanism of this action of peppermint is not known. TRPM8 channels are specific sites located in the sensory nerves of colon and spinal ganglia that respond to cool temperature and cooling sensation producing agents like peppermint. This study is aimed at characterizing the presence and functions of TRPM8 channels in mice colon. It identifies a role for TRPM8 in modulating the signals of visceral events.
- A retrograde tracer, which is a chemical used to label pathways in the nerves, was injected in the colon of the mice. These mice were then killed for dissociate ganglia cell culture (a culture of a large nerve cell, especially one of those of the spinal ganglia).
- From the dorsal root ganglion (DRG) present in the spinal column neurons, which were labeled with tracer, the percentage of the neurons in the whole DRG was worked out.
- In another part of the study, four DRGs were removed four days after injections of fluorescent dye into the colon, and the neurons were then cultured in the laboratory.
- Further, the colon was opened and the nerve fibers were dissected. The electric activity in these fibers was recorded by applying three mechanical stimuli of probing, mucosal stroking, and circular stretch.
- TRPM8 levels were measured before and after applying icilin, a cooling agent, and provoking agents like capsaicin and mustard oil.
- The results showed that 7-9% neurons in the DRG of the spinal canal were retrogradely labeled from tracer injected in the gut wall.
- Single-fiber recordings of nerve fibers showed that 24% fibers reacted directly to the cooling agent icilin.
- It was found that the nerve fiber response to chemical capsaicin, a noxious agent, was reduced when icilin was applied and electric activity in fibers was tested again.
- Mustard oil increased the nerve fiber responses to mechanical stress. This response was also found to be reduced after the application of icilin.
In IBS, abdominal pain is felt due to hypersensitivity of the gut nerves. This study explains why peppermint and certain herbal remedies reduce the symptoms of IBS. This study provides evidence for the TRPM8 expression in colonic afferent neurons. The intestinal nerve fiber and their connections in the spinal canal were identified by special tracers. The expression of TRPM8 channels that are involved in conducting sensory stimuli of cooling and altering the properties of mechanoreceptive colonic afferent endings were also studied. It was found that the application of cooling agents like icilin reduces the sensitivity of nerve fibers of the colon to mechanical stimulation. Peppermint and some herbal medicines also produce a cooling sensation and these agents might act and reduce the sensitivity of gut nerve fibers.
For More Information:
A Novel Role for TRPM8 in Visceral Afferent Function
Publication Journal: Pain, 2011
By Andrea Harrington; Patrick Hughes
From the Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia, Australia and University of Adelaide, Adelaide, South Australia, Australia
*FYI Living Lab Reports Are Summaries of the Original Research.