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Phil Tompkins wrote: > > I ran across some interesting information that is not particularly > recent, but it is new to me and probably far less well known than > it should be. I've written it up in the form of the article below. > I hope you will find it interesting. Also, I would appreciate any > further information anyone can offer on this subject. > > Phil Tompkins > Hoboken NJ > age 61/dx 1990 > > ---------------------------------------------------------------- > > The Brain in the Gut and Parkinson's Disease > > Parkinson's disease (PD) is commonly defined as a degeneration of > dopamine-producing neurons in the substantia nigra resulting in the > primary symptoms of resting tremor, stiffness, bradykinesia, and poor > balance. But there are numerous other symptoms of PD that seem > remotely, if at all, related to the substantia nigra. These include > such diverse phenomena as slowed emptying of the stomach contents > into the small intestine, sexual impotence, sweating, and seborrhea. > One may well wonder by what mechanism a deficiency of dopamine in the > substantia nigra results in some of these other symptoms. > > Dopamine is produced and used elsewhere in the body besides in the > substantia nigra. One such site is a vast neural network embedded in > the gastrointestinal tract known as the enteric nervous system (ENS). > It is becoming evident that the effects of PD on the involuntary > functions of the gastrointestinal system are associated with > degeneration of those dopamine-producing cells located not in the > substantia nigra but rather in the ENS. The mechanism by which these > effects are produced is unknown. However, evidence such as Lewy > bodies in the enteric neurons and loss of dopaminergic neurons in the > colon points to the involvement of the ENS in PD in a manner > analogous to the involvement of the brain in PD. > > Gastrointestinal effects of PD attributable to the enteric system's > involvement in the disease include reflux, delayed gastric > emptying, and decreased motility. Swallowing difficulties and > constipation, which have aspects falling under both voluntary and > involuntary control, may be the result of PD in both the brain and > the ENS. > > The ENS is located in the muscle and connective tissues that line > the digestive organs. It contains some 100 million nerves cells, > about the same number as are in the spinal chord. Many of its > structures and chemicals parallel those of the brain, which it > closely resembles at the cellular level. It has sensory and motor > neurons, supportive glial cells, information processing circuits > which transmit and process messages, and immune system cells. It > has nearly every major substance found in the brain, including all > the major neurotransmitters. Because of these resemblances, the > ENS has been called a second brain, or "the brain in the gut." > > The ENS performs two major functions. First, it regulates the > routine activity of the digestive system, by controlling the > muscles which grind food in the stomach and move it through the > digestive tract; and it regulates secretions which occur in > the digestive tract. A particlar example of a control mechanism is > the feedback loop via which detection of fat in the small intestine > prolongs retention in the stomach of its remaining contents. > > In its routine digestive role the ENS can operate quite > independently of the central nervous system, being only fine-tuned > by signals from the latter. > > The other major ENS function is to assist in preparing the organism > for facing danger. Upon receipt of a "fight or flight" signal from > the brain via the vagus nerve, the ENS activates "canned" programs > to empty the digestive system by vomiting or diarrhea and to > mobilize an immune mechanism to fight infection. > > I take the similarities between the ENS and the brain plus the > relative independence of the ENS to be further reasons to attribute > gastrointestinal PD symptoms to direct involvement of the ENS in > the disease. > > The study of Parkinson's disease as it relates to the enteric nervous > system is relatively new. There is some research in this area, but > it has not yet yielded information or drugs for managing > gastrointestinal PD symptoms. Swallowing difficulties and > constipation in PD are handled in basically the same way as they are > for people without PD. Sinemet, the principal PD drug, was designed > to deliver levodopa across the brain-blood barrier to the brain, not > to the ENS. Effects of PD drugs on the ENS are largely unknown. > > Hopefully more research will be done. The NIH has increased > funding to the new field of neurogastroenterology, and the NPF has > also provided funds. At least PD can no longer be thought of as a > disorder eminating from the central nervous system alone. > > Bibliography > > Lewis, Ricki. "Neurogastroenterologists Combine Old And New > Research Approaches." The Scientist, Vol 10, #10, pp. 13-14. May > 13, 1996. On-line at > http://www.the-scientist.library.upenn.edu/yr1996/may/ > research_960513.html. > > Quigley, Eamonn M.M. "Gastrointestinal Dysfunction in Parkinson's > Disease." Seminars in Neurology. Vol 16, #3, pp. 245-250. > September 1996. > > "Body's 'Second Brain' May Cause Digestive Disorders." The New > York Times, Jan. 23, 1996. A lot of us, and some movement disorder specialists, already know about PD effects on the autonomous and peripheral system as well as the movement centers in the brain. Some of the levodopa in the Sinemet that you take for PD movement symptoms converts to dopamine outside the brain, where it might help with troubles of digestion, constipation, thermal sensing and control, etc., were it not quickly neutralized by natural enzymes. One of these is catechol-0-methyl transferase (COMT), which is inhibited by certain new drugs such as tolcapone (Tasmar) and entacapone (Comtan). The great virtue of these COMT inhibitors is that they extend the effect of levodopa in both the central and the peripheral system. I'm impatiently waiting for general availability of Comtan, which doesn't threaten liver failure as Tasmar does. Cheers, Joe -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013