Selective autonomic and sensory deficits in slow transit constipation

Chronic idiopathic constipation is likely to be a heterogeneous condition. Our previous studies on the stimulated sweating response suggested that autonomic dysfunction may be a cause in a subset of patients. Our aims were to test selectively the neural and sweat gland components of the sweat response and to test unmyelinated sensory fibres so as to determine whether a small fibre neuropathy is present. Twelve female patients with proven slow transit constipation and nineteen age-matched healthy volunteers took part in the study. The sensory tests included thermal thresholds and axon reflex vasodilatation in response to intradermal capsaicin, measured with a laser Doppler. Direct and axon reflex sweating was induced with intradermal methacholine and nicotine, respectively, and measured with an evaporimeter. Non-parametric tests were used for statistical comparison with a group of seven control subjects. Results are expressed as medians and range. All four patients who reported constipation from childhood had a selective deficit of unmyelinated afferent fibre function in the feet, with markedly elevated thresholds to warm sensation (controls 5.2; 4.3-10.6, patients 13.8; 11.8-16.1 delta T (degree C), P < 0.02) and heat pain (controls 10.6; 8.2-14.7, patients 18.1; 13.9-22.6 delta T (degree C), P < 0.05) and a reduced response to capsaicin (controls 47.0; 24-117, patients 13.5; 12-30 delta Flux (V), P < 0.005). In contrast, patients with adult onset constipation (n = 7) had a selective neural sweating deficit (controls 49.8; 32.0-61.8; patients 27.7; 7.3-44.3 g/m2 h, P < 0.05), indicating dysfunction of post-ganglionic sympathetic cholinergic fibres. Patients from both groups were shown to have normally functioning sweat glands in direct response to methacholine. Our findings suggest that patients with severe chronic idiopathic constipation may have selective small fibre neuropathies, of which constipation is a manifestation.