Ethosuximide to Treat IBS

The irritable bowel syndrome (IBS) is characterized by a combination of discomfort and / or abdominal pain and bowel habits in the absence of identifiable organic pathology. This condition is extremely common because it is the first cause of consultation in gastroenterology and would cover 10-15% of the French. This chronic condition, although functional, impact significantly on the quality of life of patients and causes considerable health spending, making it a major public health problem. Especially as the currently used treatments are of limited effectiveness.

Among the pathophysiological mechanisms involved in IBS, visceral hypersensitivity (VHS) seems to be a major factor causing pain in patients. VHS involves sensitization of colonic nerve fibers, resulting in an increase of neuronal excitability. In several animal models of chronic pain, this hyperexcitability was related to a change in the expression or activity of ion channels, including calcium channel Cav3.2.

Investigators especially shown the involvement of Cav3.2 channels in visceral pain in an animal model of VHS. Furthermore, overexpression of these channels at the peripheral level (dorsal root ganglion innervating the colon) has been demonstrated in this animal model and pharmacological blockade, including ethosuximide, prevented the development of the VHS. Note that Cav3.2 channels have been widely demonstrated as involved in nociceptive phenomena in various animal models of chronic pain and that by blocking their ethosuximide induce an analgesic effect in these models.

Finally, we have recently demonstrated the involvement of Cav3.2 channel in patients with IBS, in a clinical case-control study. The Cav3.2 channels were overexpressed in the colonic mucosa of patients with IBS compared to asymptomatic controls.

The Cav3.2 channels are therefore a potential pharmacological target and ethosuximide a promising therapy to effectively treat the abdominal pain associated with IBS.

Inclusion criteria

• Age ≥ 18 years,

• Man,
• Women, Negative pregnancy test and effective contraception,
• IBS defined by the Rome criteria IV
• During the previous seven days the inclusion visit, average NRS pain ≥ 4,
• IBS Treatment stable for 1 month
• Patients affiliated to the French Social Security,
• Patients with the informed consent were obtained.

Exclusion criteria

• Breastfeeding
• Diabetic patients
• Known renal or hepatic impairment,
• Significant liver function abnormalities (transaminases> 3N, cholestasis) and renal (MDRD <60 ml / min)
• Addiction to alcohol and / or drugs,
• AEDs taken (epilepsy or chronic pain)
• chronic pain of greater intensity than that related to IBS,
• Allergy succinimides (ethosuximide, methsuximide, phensuximide)
• History or current severe depression (hospitalization, long-term antidepressant treatment)
• Psychotic disorders,
• Patients exclusion period, or total exceeded authorized allowances
• Patients undergoing a measure of legal protection (trusteeship, guardianship ...).