Expression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary Hyperhidrosis

doi:10.1016/j.athoracsur.2012.10.068

The Annals of Thoracic Surgery

Volume 95, Issue 2, February 2013, Pages 465-470

https://doi.org/10.1016/j.athoracsur.2012.10.068 Get rights and content

Background

The pathophysiologic characteristics of primary hyperhidrosis are not well understood and seem to be related to a sympathetic nervous system dysfunction. The resection of thoracic sympathetic chain ganglia is the most effective treatment for hyperhidrosis; however sympathetic ganglia function in normal individuals and in patients with hyperhidrosis is unknown.

Methods

A cross-sectional study, in which 2 groups of 20 subjects were analyzed: the hyperhidrosis group (HYP), comprised of patients with hyperhidrosis who were eligible for thoracic sympathectomy, and the control group (CON) comprised of brain-dead organ donors without a history of hyperhidrosis. For each subject, the following were performed: resection of the third left sympathetic ganglion, measurement of the ganglion's diameter, and immunohistochemical evaluation by quantification of strong and weak expression areas of primary antibodies against acetylcholine and alpha-7 neuronal nicotinic receptor subunit.

Results

The presence of a strong alpha-7 subunit expression area was 4.85% in patients with primary hyperhidrosis and 2.34% in controls (p < 0.001), whereas the presence of a weak expression area was 11.48% in the HYP group and 4.59% in the CON group (p < 0.001). Strong acetylcholine expression was found in 4.95% of the total area in the HYP group and in 1.19% in the CON group (p < 0.001), whereas weak expression was found in 18.55% and 6.77% of the HYP and CON groups, respectively (p < 0.001). Furthermore, diameter of the ganglia was 0.71 cm in the HYP group and 0.53 cm in the CON group (p < 0.001).

Conclusions

There is a higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis. Furthermore, the diameter of the thoracic sympathetic chain ganglia is larger in such patients.

Section snippets

Study Design

We performed a cross-sectional study in which 2 groups were analyzed: the hyperhidrosis (HYP) group, comprising patients with palmar hyperhidrosis who were eligible for thoracic sympathectomy, and the control (CON) group, comprising brain-dead organ donors without a history of hyperhidrosis. This study was approved by the Ethics Committee for Analysis of Research Projects, and all participants (or their legal guardians) provided written consent.

Setting

Ganglia resections in the HYP group were carried

Results

From December 2008 to March 2010, 47 subjects were enrolled. Four subjects were excluded because of a body mass index greater than 25 kg/m², 2 were excluded because of diabetes, and 1 was excluded because of suspected hyperhidrosis (all them in the CON group). There were no surgical complications or significant delay in the retrieval of other organs (CON group). Similarly, there was no data loss. The median participant age was 26 years (24–30.25 years) in the HYP group and 46.5 years (28.25–53

Comment

Surgical treatment of primary hyperhidrosis by video-assisted thoracic sympathectomy has improved the quality of life in a growing number of individuals worldwide every year. This procedure already accounts for a significant portion of the activity of most thoracic surgery services, yet little is known about the target organ of this operation: the sympathetic ganglion, especially among patients with hyperhidrosis, the subgroup of individuals who will be operated on [1, 3, 4, 14, 15, 16, 17, 18

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Citation Excerpt :
An important pathological cause of PFH is the dysfunction of the autonomous sympathetic nervous system. Previous studies have shown that PFH is associated with up-regulation of acetylcholine receptor subunits, choline acetyltransferase and vasoactive intestinal peptide in the thoracic sympathetic ganglia (de Moura et al., 2013). A PFH-related gene on chromosome 2q31.1 has been identified through exome sequencing and genome-wide single nucleotide polymorphism chain scan analysis in a PPH-001 family of patients with familial inheritance (Chen et al., 2015).
The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.
Symptoms of anxiety and depression in patients with primary hyperhidrosis and its association with the result of clinical treatment with oxybutynin
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Studies have identified correlations between the psychological characteristics of individuals with primary hyperhidrosis (HH), the degree of sweating, and the quality of life (QoL). This study aimed to evaluate the prevalence of anxiety and depression symptoms in patients with HH before and after oxybutynin treatment.
Data were collected from 81 patients. Palmar or axillary HH was the most frequent complaint (84.0%). All patients were evaluated before the medication was prescribed and after five weeks of treatment. The Beck Depression Inventory and Beck Anxiety Inventory were used to evaluate depression and anxiety.
Improvement in HH occurred in 58 patients (71.6%), but there was no improvement in 23 patients (28.4%). The QoL before treatment in all patients was either “poor” or “very poor.” Patients who experienced improvement in sweating rates also experienced a greater improvement in QoL than patients who did not experience improvement in sweating at the main site (87.9% vs. 34.7%) (p<0.001). A total of 19.7% of patients showed an improvement in their level of depression, and a total of 46.9% of patients exhibited improvements in their level of anxiety. A significant correlation was observed between sweating and anxiety (p=0.015).
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Original articleGeneral thoracicExpression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary Hyperhidrosis

Background

Methods

Results

Conclusions

Section snippets

Study Design

Setting

Results

Comment

J Am Acad Dermatol

J Am Acad Dermatol

J Am Acad Dermatol

Clin Neurophysiol

J Thorac Cardiovasc Surg

Auton Neurosci

Ann Thorac Surg

J Vasc Surg

Quality of life, before and after thoracic sympathectomy—report on 378 operated patients

Ann Thorac Surg

Hyperhidrosis: evolving therapies for a well-established phenomenon

Mayo Clin Proc

Ultrastructure of the hyperhidrotic eccrine sweat gland

Br J Dermatol

Original article
General thoracic
Expression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary Hyperhidrosis