© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.2.6.3 Nauseogenesis and Emetogenesis

Can the mere presence of nanorobots in the human body provoke nausea or vomiting (emesis) [2426-2433]? Vomiting is one of the most complex motor functions performed by humans. Emesis is a sequential interaction between viscera, the central nervous system, and somatic muscles that results in the expulsion of intraluminal contents from the proximal small intestine and stomach [2422]. Nausea and the act of vomiting are controlled by a region in the medulla that coordinates the respiratory and vasomotor centers and the vagus nervous innervation of the gastrointestinal tract [2421]. This “vomiting center” [2424, 2427] may be stimulated by four different sources of afferent input from:

(1) afferent vagal nerve fibers, rich in serotonin 5-hydroxytryptamine (5-HT3) receptors, and splanchnic nerve fibers in the gastrointestinal viscera that may be stimulated by biliary distention, gastrointestinal distention, mucosal or peritoneal irritation, or infections [2421]. Noxious enteric contents initiate the emetic reflex through the activity of vagal and sympathetic afferent nerve fibers that reach to the brainstem [2422]. More specifically, vomiting can be induced (a) via irritation of the gastric mucosa by the alkaloid emetine in ipecac syrup [2434], copper sulfate [2435], mercury [2436], lye [2437], or bile reflux [2438]; (b) via gastrointestinal mucosal irritation by iron salts [2439], various laxatives [2440] and pesticides [2441], mechanical irritation [2442] or duodenal [2443] or urinary [2444, 2445] obstruction, and by bile duct perforation [2446]; (c) via peritoneal irritation associated with post-anesthetic residual tissue stretching [2447] or colonic perforation [2448], acute pancreatitis [2449, 2450], or various drugs and other chemicals [2451-2453]; or even (d) via coronary artery occlusion [2433]. Emetogenic mechanoreceptors and chemoreceptors have been found in the stomach, jejunum and ileum [2433].

Properly designed medical nanorobots should not externally display or emit nauseogenic or emetogenic molecules. Massive numbers of medical nanorobots simultaneously physically traversing or cooperatively manipulating the intestinal walls (Sections 8.2.3 and 15.5.1.4, Chapter 26) could in principle produce sufficient mechanical irritation or tissue stretching to elicit emetogenesis. However, esophageal and intestinal shear forces of >~1 N/m² due to the normal passage of chyme or feces (Section 9.4.3.3) are not commonly nauseogenic. A cubic (~300 micron)³ intestinal nanorobot applying ~100 nN of lateral towing force (similar in size and strength to an amoeba; Section 9.4.3.7) also applies ~1 N/m² shear force, which likewise should not induce emesis. Amebiasis involving 12- to 50-micron motile trophozoites in the large bowel produces vomiting only in cases of severe dysenteric colitis [498], and it is not clear whether the cause of the vomiting is the number and movement of amoebae or some other factor. The presence and movements of tens of trillions (Section 8.5.1) of motile micron-sized commensal bacteria in the human colon is not normally nauseogenic.

(2) the vestibular system, having fibers with high concentrations of histamine H1 and muscarinic cholinergic receptors, which may be stimulated by motion [2454, 2455], sensory conflict [2456], or infections [2421, 2422]. Purposeful mechanical manipulations of the human vestibular (Section 7.4.6.2) or auditory (Section 7.4.6.3) sensory apparatuses by medical nanodevices could be nauseogenic or induce vertigo [2464]. These symptoms are unpleasant but not life-threatening. Nevertheless, nanorobot missions should be designed to avoid these outcomes or else the patient may require administration of the belladonna alkaloid scopolamine (a traditional prophylactic treatment for motion sickness [5498]) or other agents such as meclizine (an antihistamine with anticholinergic properties) [2422].

(3) higher central nervous system centers, including disorders of the central nervous system (e.g., elevated intracranial pressure caused by tumors [2457-2460], closed head injuries [2461], migraine and epilepsy [2461], or even intracranial amoebic invasions [2462]) or certain sights, smells, taste aversions, or emotional experiences that may induce vomiting [2421]. For example, patients receiving chemotherapy may develop vomiting in anticipation of chemotherapy; sedatives such as benzodiazepines are antiemetic for patients with anticipatory or psychogenic vomiting [2421]. Normally the presence of therapeutic nanorobots inside the human body will not be directly detectable by the human senses, but the in vivo administration of nanodevices might still elicit psychogenic emesis in worried patients who are anticipating receiving nanorobots (Chapter 17).

(4) the chemoreceptor trigger zone (CTZ) [2423-2426], rich in receptors for serotonin 5-HT3, dopamine D2, histamine and opioids, and located outside the blood-brain barrier in the area postrema of the medulla, whose chemoreceptors may be stimulated [2421, 2422, 2463] by drugs and chemotherapeutic agents [2464-2469], opioids and anesthetic agents [2472], circulating toxins or other humoral agents, hepatic amoebic invasions [2473], hypoxia [2474], uremia [2475], chlorine fumes [2476], acidosis, and radiation therapy [2425]. Barring poorly planned releases of nauseogenic effluents, medical nanorobots should not activate the CTZ.

In the highly unlikely event that nanorobots and their missions cannot be designed to be completely non-nauseogenic, many antiemetics are available [2469-2471]. Antihistamines are weakly antiemetic for “vomiting center”-mediated emesis [2421]. Blockade by serotonin 5-HT3 receptor antagonists (e.g., ondansetron [2477] and tropisetron [2467]), dopamine antagonists [2478, 2479] (e.g., metoclopramide [2479]), and NK1 [2480] antagonists is well known. Phenothiazines and related compounds specifically block CTZ-mediated vomiting [2424].

Nausea is the conscious recognition of excitation of an area in the medulla associated with the vomiting center [5489]. The sensation of nausea apparently involves the cerebral cortex [2430], and the “vomiting center” is actually a distributed control system [2428-2430] perhaps including a central pattern generator [2461, 2481] comprised of several distinct neural clusters or pathways. So most efficiently, a small number of specialized nanorobots could be stationed within (1) the vomiting center located in the nucleus tractus solitarius [2482], (2) the brain stem between the obex and the retrofacial nucleus [2430], (3) the medullary midline [2429], (4) the area postrema [2483], (5) the parabrachial nucleus [5909], and (6) certain higher brain centers [2430]. These precisely positioned specialized nanorobots could then directly control or completely extinguish all emesis-related neuron signal traffic by means previously described (Sections 4.8.6, 7.4.2.6, and 7.4.5.4), thus directly preventing nausea and vomiting.

Last updated on 30 April 2004