Local somatothermal stimulation inhibits motility of the internal anal sphincter through nitrergic neural release of nitric oxide

PURPOSE: A somatoanal reflex had been demonstrated in our previous work. Be cause nitric oxide plays an important role in mediating relaxation of the i nternal anal sphincter, our purpose was to examine whether and how local so matothermal stimulation inhibits the function of the internal anal sphincte r by stimulating nitric oxide release via nitrergic neurons and to elucidat e the possible mechanism. METHODS: The activity of the internal anal sphinc ter in anesthetized rabbits was measured by use of continuously perfused, o pen-tip manometric methods. Local somatother mal stimulation was achieved b y applying an electroheating rod 1 cm away from the skin area at the right popliteal region. The responses were further manipulated by pretreating the rabbits with agonists or antagonists linked to nitric oxide synthesis. RES ULTS: The motility of the internal anal sphincter before and during local s omatothermal stimulation was significantly different (tonic pressure (mean +/- standard error of the mean), 5.4 +/- 0.3 vs. 4.9 +/- 0.3 mmHg, P = 0.01 95; phasic pressure, 3.9 +/- 0.6 vs. 2.9 +/- 0.4 mmHg, P = 0.0002; frequenc y distribution of the phasic contractions (peak-to-peak interval), 28.9 +/- 3.7 vs 65.3 +/- 10.4 seconds, P = 0.0001). The response began at approxima tely one minute after local somatothermal stimulation when the skin tempera ture was 41 +/- 0.3 degrees C. No anal response was observed when local som atothermal stimulation was applied at the control area. The local somatothe rmal stimulation-induced internal anal sphincter relaxation was not inhibit ed by pretreatment with atropine, propranolol, or phentolamine (tonic press ure, 5.8 +/- 1 vs. 5.2 +/- 0.8 mmHg, P = 0.038; phasic pressure, 4.2 +/- 0. 9 vs. 3.1 +/- 0.6 mmHg, P = 0.020; peak-to-peak interval, 27.2 +/- 4.3 vs. 52.9 +/- 14.5 seconds, P = 0.043) but was completely blocked by pretreatmen t with a nitric oxide synthesis inhibitor. The effect of the nitric oxide s ynthesis inhibitor could be reversed by pretreatment with L-arginine (tonic pressure, 6 +/- 0.7 vs. 5.6 +/- 0.7 mmHg, P = 0.047; phasic pressure, 4.7 +/- 0.7 vs. 3.9 +/- 0.5 mmHg, P = 0.048; peak-to-peak interval, 23.8 +/- 3 vs. 33 +/- 3.7 seconds, P = 0.048), but not by D-arginine. CONCLUSION: Loca l somatothermal stimulation inhibits internal anal sphincter motility throu gh the activation of nonadrenergic noncholinergic neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of anorectal diseases with hypofunction of the L-arginine/nitric oxide pat hway.