Neural control of the gastrointestinal tract: Implications for Parkinson disease

Abstract

Disorders of swallowing and gastrointestinal motility are prominent nonmotor manifestations of Parkinson disease (PD). Motility of the gut is controlled both by extrinsic inputs from the dorsal motor nucleus of the vagus (DMV) and paravertebral sympathetic ganglia and by local reflexes mediated by intrinsic neurons of the enteric nervous system (ENS). Both the ENS and the DMV are affected by Lewy body pathology at early stages of PD. This early involvement provides insights into the pathophysiology of gastrointestinal dysmotility in this disorder and may constitute an important step in the etiopathogenesis of Lewy body disease.

Medical records documentation of constipation preceding Parkinson disease

“…24,25 Indeed, Lewy bodies have frequently been reported in the autonomic nervous system of persons with incidental Lewy body disease, which is thought to reflect preclinical PD (Braak stages 1-2). 14,[26][27][28][29] This contrasts with the later involvement of the substantia nigra, the substrate for the motor findings of PD, which becomes manifest only during more advanced Braak stages (Braak stages 3-4).…”

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

“…Neuropathologic studies consistently demonstrate the involvement of the enteric nervous system [9,[49][50][51][52] and the dorsal motor nucleus of the vagus (DMV) based on alpha-synuclein histopathology [53,54]. These symptoms are classified as drooling, pharyngeal or esophageal dysmotility, early satiety and nausea, constipation and defecatory dysfunction, as elegantly summarized in a review by Cerosimo and Benaroch [55]. Chronic constipation most likely reflects a loss of neurons in the myenteric plexus [56,57] and may also occur as a manifestation of the age-related neurodegeneration of the ENS [58].…”

Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis

“…Although the movement disorder has dominated the attention of clinicians and researchers, it is becoming increasingly recognized that PD also involves a prominent nonmotor pathology. In fact, patients with PD experience a remarkably broad spectrum of prodromic nonmotor symptoms that include sleep disorders, orthostatic hypotension, and gastrointestinal (GI) dysfunctions, all of which add significantly to the overall disability caused by PD (9,22,26,33,38,42).GI symptoms, such as dysphagia, nausea, delayed gastric emptying and dysmotility, and constipation, often precede the onset of motor symptoms; indeed, their occurrence in otherwise healthy people has been associated with an increased PD risk (9,14,27,40). Furthermore, the GI-related dysfunctions experienced by patients with PD often adversely impact the quality of life, and, perhaps worse, their management is limited and often restricted to supportive measures (38, 47).…”

“…Although the movement disorder has dominated the attention of clinicians and researchers, it is becoming increasingly recognized that PD also involves a prominent nonmotor pathology. In fact, patients with PD experience a remarkably broad spectrum of prodromic nonmotor symptoms that include sleep disorders, orthostatic hypotension, and gastrointestinal (GI) dysfunctions, all of which add significantly to the overall disability caused by PD (9,22,26,33,38,42).…”