Ghrelin levels in patients with ACNES (Anterior Cutaneous Nerve Entrapment Syndrome) and gastrointestinal complaints, loss of appetite and weight loss.

Rationale: The abdominal wall is an under recognized cause of abdominal pain, often due to the anterior cutaneous nerve entrapment syndrome (ACNES) (1-3). This is caused by unknown triggering of the anterior and lateral cutaneous branches of anterior rami of thoracic intercostal nerves 7th-12th penetrating the rectus abdominis muscle. These nerves innervate the abdominal wall sensory (4). Our centre has noticed that about half of the ACNES patients exhibit a range of so called pseudovisceral complaints such as bloating, relation of pain to food ingestion, nausea, weight loss, etc. (5). We hypothesize that these symptoms may reflect a disturbed segmental relation between a viscus and a dermatoma resulting in a Head zone (6). Following this line of thought, the effect of percutaneous electrical neurostimulation of these nerves was recently evaluated in a RCT in obese patients. It was concluded that stimulation of Th 6 nerves resulted in a significant loss of appetite and weight loss that was most probably due to the creation of a somato-autonomic reflex (7). The same research group described a direct correlation between appetite reduction and ghrelin reduction after treatment with electrical neurostimulation at Th 6 nerve level in obese patients (10). Ghrelin is a peptide hormone produced by mainly the gastric fundus that induces appetite. The aim of this study is to demonstrate that there is an association between ACNES and pseudovisceral complaints, We hypothesize that in patients with ACNES and visceral complaints with a loss of appetite and weight loss, ghrelin levels are lowered. The results of this study could learn us more of the etiology of ACNES.

Objective: The aim of this study is to verify our theory of an association between ACNES and pseudovisceral symptoms. We hypothesize in this study that fasting ghrelin blood level in ACNES patients with pseudovisceral symptoms and weight loss is lowered in comparison with a healthy control group.
Study design: Matched pilot study with 40 participants ( intervention group n= 20, control group n=20).

Study population:
- Intervention group: ACNES patients with visceral complaints and weight loss, age 18-65, BMI <30.
- Control group: healthy volunteers without ACNES, age 18-65, BMI <30.

Intervention:
- Intervention group: at baseline and 6 weeks after last treatment a fasting venepuncture and questionnaire. During treatment optional questionnaires.
- Control group: at baseline questionnaire for selection and after selection a fasting venepuncture.

Main study parameters/endpoints:
- The difference in fasting ghrelin blood level between ACNES patients and a healthy control group.
- The difference in fasting ghrelin blood level before and after treatment for ACNES.
- The difference in fasting ghrelin blood level after treatment for ACNES between the ACNES patients with a successful therapy and those with a failed therapy.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients do not benefit of participation in this study but the outcome of this study can contribute to the knowledge of ACNES. Patients receive investigation and treatment as by standard of care for ACNES. There are no major risks involving fasting venepuncture. Timing will be in consultation with the patient (day of surgery, with consultation in the morning, etc.).

The aim of the primary objective is to verify our theory ( `proof of concept`) of an association between ACNES and pseudovisceral symptoms. This will give us more insight in the etiology of ACNES. Our theory is that these pseudovisceral symptoms may be a reflection of a compromised or disturbed segmental relation between the viscus and the thoracic nerve resulting in a painful head zone. We hypothesize in this study that fasting ghrelin blood level in ACNES patients with pseudovisceral symptoms and weight loss is lowered in comparison with a healthy control group.
Secondary objective is to investigate a change in ghrelin blood levels in ACNES patients before and after their treatment. Our theory is that after successful treatment patients do not experience the visceral complaints anymore. Thereby, we hypothesize that ghrelin blood level is changed to more normal levels. We are also interested in a possible association between treatment outcome (success versus failure) and ghrelin blood levels. In this case, we hypothesize that ghrelin blood level is not changed after a failed treatment.

Baseline (week 0) : start of the study before treatment
• Use of data in the EPD
• Additional questionnaire (see F1a)
• One fasting blood sample by venepuncture at our hospital
During treatment (optional)
• Use of data in the EPD
• Additional questionnaire in follow-up (see F1a) for changes in weight, medication and medical conditions if patient is visiting our outpatient department
6 weeks after finishing treatment (week 6 - month 6): study end
• Use of data in the EPD
• Additional questionnaire (see F1a)
• One fasting blood sample by venepuncture at our hospital

Questionnaire and 2 samples of fasting blood by venepuncture.