Nanomedicine, Volume IIA: Biocompatibility

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

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

Could the presence of inhaled or perambulating medical nanorobots in the nasal passages induce sternutation (sneezing)? A sneeze involves dozens of muscles in the face, chest and abdomen, all operating in a correct sequence that has been hardwired in the brain and spinal cord [2290, 2291]. The sequence is mediated by the trigeminal nerve, particularly the anterior ethmoidal, posterior nasal, and infraorbital nerve branches [2292]. Most of the branches of the trigeminal nerve end in the facial skin where they carry messages serving the sense of touch (including temperature and pain), but some branches end in the nasal mucosa just below the surface [2290]. The nasal mucosa is densely innervated by small-diameter myelinated sensory nerve fibers [2293] ending in receptors [2294] located in and under the epithelium [2295, 2296]. Some nerve endings are chemically sensitive and respond to irritating odors to trigger a sneeze [2290, 2295]. Other types of nerve ending respond to touch or mechanical stimulation. Irritation of the nasal passages excites nerve impulses that travel through the trigeminal ganglion to a set of neurons collectively known as the sneezing center in the lateral medulla [2297], located in the lower brainstem (medulla oblongata). The sneeze reflex in humans occurs in two phases [2298]. During the nasal phase, the sneezing center sends impulses along the facial nerve back to the nasal passages and face, causing the nasal passages to secrete fluid and become congested, and the eyes to water. During the subsequent respiratory phase, the sneezing center sends impulses to respiratory muscles via the spinal cord, causing the characteristic deep inspiration and forceful expiration of air [2299].

Many stimuli can trigger a sneeze [2299], including nasal infections, allergies (e.g., pollens and molds), cold air and humidity, chemical irritants [2311] such as spices [2300] (mean level 0.15 mg/m3 [2301]) or ammonia [2290], newspaper dust [2302], 2- to 10-micron oil mists at 0.1-0.3 mg/m3 (~106 particles/m3) [2303], exposure to bright sunlight (autosomal-dominant photic sneeze reflex [2304] affecting 18-35% of the population [2305]), overeating, sexual excitement, hair pulling or eyebrow plucking, shivering, repetitive electrical stimulation [2306, 2307], catheter-delivered air puffs to the superior nasal meatus [2308], or a needle inserted into the orbital cavity [2309]. Sneezing can be a purely allergic reaction, accompanied by histamine and neuropeptide release [2310-2312] that can be locally suppressed using drugs like NSAIDs or Azelastine [2313]. However, nanorobots should be designed to be chemically and allergenically inert, so the most likely source of nanorobot sternutatogenicity is mechanical stimulation (c.f., a nylon fiber applied to the nasal mucosa [2314]). The most likely source of such stimulation in a nanomedical context is the physical motions of nanorobots moving across the surfaces of the nasal passages.

Precise measurements of the threshold stimulus needed to activate nasal mechanosensors have not yet been reported. However, the minimum detectable skin pressure, which occurs on tongue and fingertip, is ~2000 N/m2 (Section 9.5.2), and intranasal pressure during sneezing is ~600 N/m2 in adults [2315] and ~700 N/m2 in premature newborns [2316]. Mechanical stimulation of cat nasal membrane at 20 Hz with a peak-to-peak displacement of 500 microns evoked the sneeze reflex [2317]. Assuming the area compressibility modulus for this membrane is ~1 N/m (Section, the required displacement pressure was ~2000 N/m2. Assuming ~1000 N/m2 as the activation threshold for mechanically-stimulated sneezing (based on the aforementioned pressure values), and assuming the minimum value for mucus viscosity (Table 9.4), Eqn. 9.73 suggests that the viscous motive forces required to propel a spherical 1-micron diameter nanorobot through the mucus at a speed of ~1 cm/sec or slower (force <~1 nN, power <~10 pW power) should be insufficient to trigger the sneeze reflex. Thicker nasal mucus would demand slower locomotion to hold applied forces below the assumed threshold limit for sneezing, especially since nasal inflammation undoubtedly makes these reflexes more sensitive [5821]. These questions can be resolved by simple laboratory experiments.


Last updated on 30 April 2004