Science Topics – 104

The descending pain inhibitory pathways activate the spinal defecation centre
Kiyotada Naitou(Yasutake Shimizu)

Gastrointestinal dysmotility in patients with irritable bowel syndrome (IBS) and the Parkinson’s disease is a significant clinical problem. It is apparent that constipation and/or diarrhea associated with these diseases are caused by dysfunction of central nervous system rather than that of peripheral enteric nervous system. However, precise mechanisms for controlling intestinal motility by the central nervous system are still unclear. There are two centres controlling defecation in the lumbosacral spinal cord and brain, which termed the spinal defecation center and supraspinal defecation centre, respectively. We have investigated mechanisms that the spinal defecation centre controls colorectal motility. In present studies, we demonstrated that intrathecally administrated noradrenaline1) or dopamine2) enhances colorectal motility. Noradrenaline or dopamine activates preganglionic neurons of the sacral parasympathetic nerve through alpha-1 adrenoceptor or D2-like dopamine receptor, respectively.

It is well known that noradrenaline and dopamine are associated with regulation of pain in the spinal cord. Almost all spinal noradrenaline and dopamine are derived from the brain. Therefore, the descending noradrenergic and dopaminergic pathways are termed descending pain inhibitory pathways. Our results propose a novel theory that descending pain inhibitory pathways control not only pain but also defecation reflexes (Figure). We expect that the theory would provide new insight into studies about pathophysiological mechanisms of IBS. Since hypersensitivity is occurred in the large intestine of IBS patients, descending pain inhibitory pathways would be over activated and result in the bowel dysfunction. In patients with Parkinson’s disease, degeneration of dopaminergic neurons in the central nervous system causally attenuates dopamine release in the spinal defecation centre, yielding chronic constipation. We believe that our results may have important implications for elucidating pathophysiology of gastrointestinal dysmotility related to functional disorders in the central nervous system.

1)Naitou K, Shiina T, Kato K, Nakamori H, Sano Y, Shimizu Y. Colokinetic effect of noradrenaline in the spinal defecation center: implication for motility disorders. Sci Rep. 2015. 5:12623. doi: 10.1038/srep12623.
2)Naitou K, Nakamori H, Shiina T, Ikeda A, Nozue Y, Sano Y, Yokoyama T, Yamamoto Y, Yamada A, Akimoto N, Furue H, Shimizu Y. Stimulation of dopamine D2-like receptors in the lumbosacral defecation centre causes propulsive colorectal contractions in rats. J Physiol. 2016. in press, doi: 10.1113/JP272073.

Department of Basic Veterinary Science, Laboratory of Physiology, The United Graduate School of Veterinary Sciences, Gifu University