J. Physiol. (1969), 204, pp.

91-98 91
With 3 text-ftgure8
Printed in Great Britain

EPIPHARYNGEAL RECEPTORS RESPONDING TO

MECHANICAL STIMULATION
BY B. S. NAIL, G. M. STERLING AND J. G. WIDDICOMBE
From the University Laboratory of Physiology, Oxford
(Received 3 February 1969)
SUMMARY
1. Action potentials were recorded from twenty-one afferent nerve
fibres from receptors in the epipharynx in anaesthetized, paralysed cats.
Sixteen of the fibres had no spontaneous discharge.
2. Gentle mechanical stimulation of the epithelium of the epipharynx
with a nylon fibre caused all twenty-one receptors to discharge with
rapidly adapting bursts of impulses at a mean peak frequency of 197
impulses/sec.
3. Stimulation with a stream of air through the epipharynx sufficient to
distend the whole pharynx caused seven out of twelve receptors to dis-
charge in rapidly adapting bursts. Stimulation with a jet of air directly on
to the epithelium of the epipharynx caused seven out of nine receptors to
discharge.
4. Chemical stimulation of the epipharynx with ammonia vapour caused
an increased discharge in only three out of twenty receptors, and intra-
venous histamine had no effect on the four units tested.
5. It is concluded that the receptors mediate the 'aspiration reflex'
elicited by mechanical stimulation of the epipharyngeal mucosa.

INTRODUCTION
In the cat, mechanical stimulation of the epithelium of the epipharynx,
dorsal to the free border of the soft palate and just cranial to the insertion
of the soft palate in the lateral wall of the pharynx (Fig. 1), causes broncho-
dilatation, hypertension and repeated rapid contractions of the diaphragm
(Ivanco & Korpas, 1954; Ivanco, Korpas & Tomori, 1956; Takagi, Irwin
& Bosma, 1966; Tomori & Widdicombe, 1969). This response has been
called the 'aspiration reflex' (Tomori, 1965) and can also be caused by
electrical stimulation of the pharyngeal branch of the glossopharyngeal
nerve (Nail, Sterling & Widdicombe, 1969), which is the main afferent
supply of the region described above. Electrophysiological analysis of the

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92 B. S. NAIL AND OTHERS
motor side of this reflex has shown the occurrence of short bursts of very
rapid discharge in phrenic motoneurones in response to stimulation of the
epipharynx (Tomori & Widdicombe, 1969), and corresponding to the
diaphragmatic twitches seen in spontaneously breathing animals. Expira-
tory muscle motoneurones do not increase their discharge. Inspiratory
intercostal motoneurones show a similar response to that of the phrenic
nerves (B. S. Nail, G. M. Sterling and J. G. Widdicombe, unpublished).
The afferent side of the reflex has not been examined previously and this
paper describes the electrical activity in the pharyngeal branch of the
glossopharyngeal nerve during stimulation of the epipharynx.

METHODS
Four cats weighing 1-6-3-0 kg were anaesthetized with intraperitoneal pento-
barbitone sodium, 32 mg/kg. The trachea was cannulated just below the cricoid
cartilage. Femoral arterial and venous catheters were inserted, the former for con-
tinuous monitoring of arterial blood pressure with a strain gauge transducer (Con-
solidated Electrodynamic), and the latter for injection of further anaesthetic or other
drugs. Intratracheal pressure was measured with an air-filled catheter and capaci-
tance manometer (Infra-red Devp. Co.). End-tidal CO2 % was followed continuously
with a rapid infra-red analyser (Beckman LBI). Records of blood pressure and
tracheal pressure together with action potentials from nerve fibres were displayed
on a five-channel oscilloscope (Tektronix 551) and were photographed or recorded on
magnetic tape (Thermionix T 1000) for subsequent analysis.
The region high on the dorsal wall of the pharynx which was to be stimulated was
approached in two of the cats through a small hole made in the side-wall of the
pharynx just cranial to the wing of the hyoid bone. This revealed the free border of
the soft palate, behind which it was possible to reach the epipharynx. In the other
two cats the ventral wall of the pharynx, including the body of the hyoid bone, was
excised widely, so that the epipharyngeal epithelium could be stimulated under
more direct vision.
The largest branch of the glossopharyngeal nerve emerges from the pharyngeal
wall deep to the lingual artery and nerve to join the carotid sinus nerve at the base
of the skull. This 'pharyngeal branch' was carefully dissected out and cut as near as
possible to its junction with the carotid sinus nerve, and the distal cut end was then
teased out into single or few-fibre strands. Action potentials from these were re-
corded via bipolar platinum electrodes and after amplification (Tektronix 122 pre-
amplifier) were displayed on the oscilloscope.
Before recording was started, the cats were paralysed with gallamine triethiodide,
20 mg, and were then maintained on artificial positive pressure ventilation at 40-50
c/min. Stroke volume of the pump was adjusted to keep end-tidal CO2 % close to the
level observed during spontaneous breathing.
The dorsal wall of the epipharynx above and behind the free border of the soft
palate (Fig. 1) was stimulated mechanically with a fine nylon fibre inserted through
the hole in the side wall or the ventral surface of the pharynx. Small movements of
the fibre against the epithelium of the epipharynx were made by hand, the distortion
of the mucosa being kept to a minimum.
The effect of air flow on the epipharyngeal receptors was tested by blowing dry
air at 6 I./min through a catheter inserted into one nostril. The air escaped from the

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 EPIPHARYNGEAL RECEPTORS 93
pharynx mainly through the hole in the side wall used for mechanical stimulation.
By loosely closing this hole (so that the air now left by the tracheostomy opening)
it was possible to increase the amount of distension and deformation of the pharynx
due to air flow. In the cats in which the ventral wall of the pharynx had been widely
excised, a jet of air, usually at 1 1./min, was played directly on to the epithelium of
the epipharynx through a wide bore needle.
Chemical stimulation of epipharyngeal receptors was attempted by injecting 3-5
ml. strong ammonia vapour into a constant stream of air flowing through, or on to,

Fig. 1. Diagrammatic sagittal section of the mouth and pharynx of the

cat. Arrows mark area of mechanical stimulation of the dorsal wall of the
epipharynx.

the epipharynx. The ammonia vapour was obtained from the gas phase of a bottle
containing ammonia solution. On one occasion chemical stimulation by direct appli-
cation of 10 % C02 in air to the epithelium was attempted. Intravenous injection of
histamine acid phosphate, 50 jig/kg, was used in four experiments.

RESULTS
Mechanical stimulation
There was little spontaneous activity in the pharyngeal branch of the
glossopharyngeal nerve. All strands were tested by mechanical stimulation
of the epithelium of the epipharynx. If this caused a discharge, the strand
was teased out to make single fibre preparations.
Twenty-one single fibre units were studied. The majority were silent in
the absence of mechanical stimulation but five showed some irregular
spontaneous activity. Control discharge rates were generally slow, with
transient maximum frequencies of less than 30/sec. The action potentials

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94 B. S. NAIL AND OTHERS
A 120
200 I
100 E
M

I
1 sec
B

1j-
VTF
I*I.
iitIri
I I Ij
.
3-r
- ] .
I
i

C D

Fig. 2. Blood pressure, and action potentials in a strand of the pharyngeal

branch of the glossopharyngeal nerve during stimulation of the epipharynx.
A, 3 ml. ammonia vapour at signal; no response. B, Mechanical stimulation
with nylon fibre during signal; transient discharges with each movement
of the thread (blood pressure trace damped in A and B due to a clot in the
arterial catheter). C and D, Air flow at 6 1./min through a catheter in the
left nostril; rapidly adapting discharges at the start of air flow only. Long
horizontal bars mark the duration of each stimulus.
0, 20 200
U
CL *-
E 2c100 E
W....
WL . ......6.
.

I sec

-~~~~~~~~~~~~~~~~~~~~~~~~~---- - - - -----------
I. ~~~
~~~~~~~~~~~~~~~
Fig. 3. Blood pressure, tracheal pressure (TP) and action potentials in a
strand of the pharyngeal branch of the glossopharyngeal nerve during
stimulation by airflow at 6 1./min through the epipharynx. Upper record:
air flow with the hole in the pharyngeal wall open (little pharyngeal dis-
tension). Lower record: air flow with the hole in the pharyngeal wall closed
(greater pharyngeal distension). The horizontal bars indicate the durations
of air flow.

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 EPIPHARYNGEAL RECEPTORS 95
were typical of myelinated fibres (Figs. 2 and 3), but the nerve was not
long enough to determine conduction velocities.
With all the receptors, gentle mechanical stimulation caused rapid
bursts of impulses up to 330/sec (mean = 197, range 67-330 impulses/sec).
With a maintained steady pressure on one point the discharge was rapidly
adapting, but repeated bursts of impulses could be caused by small move-
ments of the stimulating fibre. A representative response is shown in Fig.
2 B, where five separate short bursts of impulses occurred in response to
repetitive mechanical stimulation of the epithelium.
Air flow
Air flow stimulated 14 of 21 receptors tested. Typical, rapidly adapting
responses are shown in Fig. 2C and D. In the experiments in which a jet
of air was played on the epipharyngeal epithelium under direct vision it
could be seen to cause local deformation of the tissues in the form of a
small dimple. Under these conditions seven out of nine receptors increased
their discharge rate, the maximum response being at a frequency of 330
impulses/sec (for the seven receptors, mean = 192, range 56-330
impulses/sec).
In the other experiments, air was blown through the pharynx at 6 L./
min via a catheter in one nostril. When the hole in the side wall of the
pharynx was closed (see Methods), there was visible distension of the whole
pharynx and seven out of twelve receptors showed characteristic rapidly
adapting discharges forming small bursts of impulses at the start, and
sometimes also at the end, of each period of air flow (for the seven receptors,
mean = 182, range 36-330 impulses/sec). The size of the response appeared
to be related to the degree of distension of the pharynx, and discharges
from the same receptor during air flow with the pharyngeal hole open and
closed are illustrated in Fig. 3.
Chemical stimulation
When 3-5 ml. strong ammonia vapour was added to a constant stream
of air flowing through the pharynx only three out of twenty receptors
showed an increased discharge rate. The impulse frequencies were 5, 38
and 140 impulses/sec. The last and strongest response may not have been
primarily due to chemical stimulation, since this particular receptor also
showed some increase in discharge, presumably due to transient mechanical
stimulation, when 3 ml. air (without ammonia) was injected into the
constant stream of air.
On the one occasion on which a receptor was tested with 10 % CO2
blown directly on to the epipharyngeal epithelium, without distortion of
the mucosa, there was no change in discharge rate. Similar negative results

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96 B. S. NAIL AND OTHERS
were obtained after intravenous histamine, 50 /sg/kg, tested on four
receptors.
DISCUSSION
Mechanical stimulation of the epipharynx in the cat causes a series of
rapid contractions of the diaphragm, called the 'aspiration reflex' (Ivanco
& Korpas, 1954; Takagi et al. 1966; Tomori, 1965). Electrical stimulation
of the pharyngeal branch of the glossopharyngeal nerve elicits the same
diaphragmatic response (Nail et al. 1969). The expiratory muscles do not
contract. The properties of the receptors we have studied indicate that they
mediate this 'aspiration reflex'.
Our results suggest that the end-organs are mainly mechanoreceptors,
sensitive to deformation of the epithelium or sub-epithelium of the
epipharynx. Thus they consistently discharge on small movements of the
epithelium caused by a fine nylon filament, and are also stimulated by
distension of the whole pharynx by a flow of air whose escape is impeded.
When the same flow of air is accompanied by less distension the receptors
discharge less, and it therefore seems likely that they respond to mechanical
deformation of the epipharynx rather than to any surface effect of the air
flow. This suggestion is supported by the finding that, under direct vision
with a fine jet of air, discharge in afferent nerve fibres is associated with a
'dimple' of the epithelium.
Conversely, the receptors do not appear to be chemosensitive, since only
in rare instances do they respond to strong ammonia vapour, and then
only rather weakly. On the few occasions on which they were tested they
did not respond to intravenous histamine. Thus it seems unlikely that
these receptors can mediate any sensory or reflex responses to chemical
irritation in the epipharynx.
The properties of the epipharyngeal receptors may be compared with
those of epithelial endings lower in the respiratory tract. Cough receptors
or irritant receptors in the trachea and bronchi are mechano-sensitive and
rapidly adapting; many respond to chemical irritants such as ammonia,
and their chemosensitivity seems to increase in relation to their depth in
the tracheobronchial tree (Widdicombe, 1954). Epithelial receptors in the
lungs are stimulated by injections of histamine, but this effect is mainly
due to contraction of associated smooth muscle (Mills, Sellick & Widdi-
combe, 1969). The epithelium of the larynx and epiglottis also contains
rapidly adapting mechanosensitive endings (Andrew, 1956; Franken-
haeuser, 1948), but their responses to chemical irritants do not seem to
have been tested. Thus epithelial receptors throughout the respiratory
tract are similar in that they give rapidly adapting responses to mechanical
deformation, but their reflex actions on the inspiratory and expiratory

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 EPIPHARYNGEAL RECEPTORS 97
muscles, and on the cardiovascular system and bronchomotor tone, differ
profoundly according to the receptor site (Tomori & Widdicombe, 1969).
Our experimental procedure was designed to select fibres from epithelial
endings responding to gentle touch of the mucosa with a nylon fibre.
Deeper receptors, such as muscle spindles and joint receptors, would
probably not be stimulated by this method. Some such endings were
identified, but since they did not respond to the gentle mechanical stimu-
lation that elicits the aspiration reflex, they are not included in this
description.
There seems to be no information on the histological structure of the
epipharyngeal receptors. Their role in the intact animal is also obscure,
but probably not negligible, since their stimulation provokes a strong
motor response capable of disrupting and replacing the normal pattern of
respiration. However, there are species differences, the dog and rabbit
apparently lacking an 'aspiration reflex' (Teitelbaum & Ries, 1935) though
it is present in the new-born human and pig (Takagi et al. 1966). The last
authors have suggested that the reflex may be important in maintaining
a normal ventilatory pattern, since the latter may be lost after tracheotomy
in the human neonate. Our results indicate that the receptors will only be
stimulated in eupnoea if the aerodynamic events appreciably distort the
epipharyngeal wall.
B.S.N. is a Nuffield Dominions Demonstrator. G.M.S. is an M.R.C. Clinical
Research Fellow. Part of the apparatus used was bought with grants from the Royal
Society and the M.R.C. We are grateful to Mrs M. Jolly and Mr F. O'Connor for their
efficient technical help, and to Dr Z. Tomori for his advice and discussion.

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