Escolar Documentos
Profissional Documentos
Cultura Documentos
y
Recent studies (39-41) have shown
that volleys of nerve impulses in large S
fibers are extremely effective initially
in activating the T cells but that their
later effect is reduced by a negative
feedback mechanism. In contrast, vol- Fig. 4. Schematic diagram of the gate control theory of pain mechanisms: L, the
leys in small fibers activate a positive large-diameter fibers; S, the small-diameter fibers. The fibers project to the substantia
feedback mechanism which exaggerates gelatinosa (SG) and first central transmission (T) cells. The inhibitory effect exerted by
SG on the afferent fiber terminals is increased by activity in L fibers and decreased by
the effect of arriving impulses. Experi- activity in S fibers. The central control trigger is represented by a line running from
ments (37, 39, 41) have shown that the large-fiber system to the central control mechanisms; these mechanisms, in turn,
these feedback effects are mediated by project back to the gate control system. The T cells project to the entry cells of the
cells in the substantia gelatinosa. Ac- action system. +, Excitation; —, inhibition (see text).
tivity in these cells modulates the
membrane potential of the afferent
fiber terminals and thereby determines If the stimulus intensity is increased, that pain results after prolonged moni-
the excitatory effect of arriving im- more receptor-fiber units are recruited toring of the afferent input by central
pulses. Although there is evidence, so and the firing frequency of active units cells. First, threshold for shock on one
far, for only presynaptic control, there is increased (9, 24). The resultant pos- arm is raised by a shock delivered as
may also be undetected postsynaptic itive and negative effects of the large- long as 100 milliseconds later to the
control mechanisms that contribute to fiber and small-fiber inputs tend to other arm (43). Second, in pathologi-
the observed input-output functions. counteract each other, and therefore cal pain states, delays of pain sensa-
We propose that three features of the output of the T cells rises slowly. tion as long as 35 seconds after stimu-
the afferent input are significant for If stimulation is prolonged, the large lation cannot be attributed to slow con-
pain: (i) the ongoing activity which fibers begin to adapt, producing a rela- duction in afferent pathways (10). We
precedes the stimulus, (ii) the stimu- tive increase in small-fiber activity. As suggest, then, that there is temporal
lus-evoked activity, and (iii) the rela- a result, the gate is opened further, and spatial summation or integration
tive balance of activity in large versus and the output of the T cells rises of the arriving barrage by the T cells.
small fibers. The spinal cord is con- more steeply. If the large-fiber steady The signal which triggers the action
tinually bombarded by incoming nerve background activity is artificially raised system responsible for pain experience
impulses even in the absence of ob- at this time by vibration or scratch- and response occurs when the output
vious stimulation. This ongoing activ- ing (a maneuver that overcomes the of the T cells reaches or exceeds a
ity is carried predominantly by small tendency of the large fibers to adapt), critical level. This critical level of fir-
myelinated and unmyelinated fibers, the output of the cells decreases. ing, as we have seen, is determined by
which tend to be tonically active and Thus, the effects of the stimulus- the afferent barrage that actually im-
to adapt slowly, and it holds the gate evoked barrage are determined by (i) pinges on the T cells and has already
in a relatively open position. When a the total number of active fibers and undergone modulation by substantia
stimulus is applied to the skin, it pro- the frequencies of nerve impulses that gelatinosa activity. We presume that
duces an increase in the number of ac- they transmit, and (ii) the balance of the action system requires a definite
tive receptor-fiber units as information activity in large and small fibers. time period for integrating the total
about the stimulus is transmitted to- Consequently, the output of the T cells input from the T cells. Small, fast
ward the brain. Since many of the may differ from the total input that variations of the temporal pattern
larger fibers are inactive in the ab- converges on them from the peripheral produced by the T cells might be in-
sence of stimulus change, stimulation fibers. Although the total number of effective, and the smoothed envelope
will produce a disproportionate rela- afferent impulses is a relevant stimulus of the frequency of impulses—which
tive increase in large-fiber over small- parameter, the impulses have different contains information on the rate of
fiber activity. Thus, if a gentle pres- effects depending on the specialized rise and fall, the duration, and the
sure stimulus is applied suddenly to functions of the fibers that carry them. amplitude of firing—would be the ef-
the skin, the afferent volley contains Furthermore, anatomical specialization fective stimulus that initiates the ap-
large-fiber impulses which not only fire also determines the location and the propriate sequence of activities in the
the T cells but also partially close the extent of the central terminations of cells that comprise the action system.
presynaptic gate, thereby shortening the fibers (24, 41, 42). Central control trigger. It is now
the barrage generated by the T cells. There are two reasons for believing firmly established {44) that stimula-
19 NOVEMBER 1965 975
tion of the brain activates descending carry two-point discrimination, rough- components of the whole experience,
efferent fibers (45) which can influ- ness discrimination, spatial localiza- such as rubbing the damaged area,
ence afferent conduction at the earliesttion, tactile threshold, and vibration avoidance behavior, and so forth.
synaptic levels of the somesthetic sys- (48). Complex discrimination and lo- The perceptual awareness that accom-
tem. Thus it is possible for central calization, however, are not a modal- panies these events changes in quality
nervous system activities subserving at-ity; they represent decisions based on and intensity during all this activity.
tention, emotion, and memories of an analysis of the input. Indeed, the This total complex sequence is hidden
prior experience to exert control over traditional view is questionable in the in the simple phrases "pain response"
the sensory input. There is evidence light of Cook and Browder's (49) ob- and "pain sensation." The multiplicity
(44) to suggest that these central in- servation that surgical section of the of reactions demands some concept of
fluences are mediated through the gate dorsal columns produced no perma- central mechanisms which is at least
control system. nent change in two-point discrimina- capable of accounting for sequential
The manner in which the appropri- tion in seven patients. patterns of activity that would allow
ate central activities are triggered into The second candidate for the role the complex behavior and experience
action presents a problem. While some of central control trigger is the dorso- characteristic of pain.
central activities, such as anxiety or Iateral path (50), which originates in The concept of a "pain center" in
excitement, may open or close the gate the dorsal horn and projects, after re- the brain is totally inadequate to ac-
for all inputs at any site on the body, lay in the lateral cervical nucleus, to count for the sequences of behavior
others obviously involve selective, lo- the brain stem and thalamus. This sys- and experience. Indeed, the concept is
calized gate activity. Men wounded in tem has small, well-defined receptive pure fiction, unless virtually the whole
battle may feel little pain from the fields (51) and is extremely fast; in brain is considered to be the "pain
wound but may complain bitterly spite of having one additional relay, center," because the thalamus (7, 25),
about an inept vein puncture (13). it precedes the dorsal column-medial the limbic system (54), the hypothala-
Dogs that repeatedly receive food im- lemniscus volley in the race to the mus (55), the brain-stem reticular for-
mediately after the skin is shocked, cortex (52). mation (56), the parietal cortex (57),
burned, or cut soon respond to these Both these systems, then, could ful- and the frontal cortex (14) are all
stimuli as signals for food and salivate,
fill the functions of the central control implicated in pain perception. Other
without showing any signs of pain, yet trigger. They carry precise informa- brain areas are obviously involved in
howl as normal dogs would when the tion about the nature and location of the emotional and motor features of
stimuli are applied to other sites on the stimulus, and they conduct so the behavior sequence. The idea of a
the body (16). The signals, then, must rapidly that they may not only set the "terminal center" in the brain which
be identified, evaluated in terms of receptivity of cortical neurons for sub- is exclusively responsible for pain sen-
prior conditioning, localized, and in- sequent afferent volleys but may, by sation and response therefore becomes
hibited before the action system is ac- way of central-control efferent fibers, meaningless.
tivated. We propose, therefore, that also act on the gate control system. We propose, instead, that the trig-
there exists in the nervous system a Part, at least, of their function, then, gering of the action system by the T
mechanism, which we shall call the could be to activate selective brain cells marks the beginning of the se-
central control trigger, that activatesprocesses that influence information quence of activities that occur when
the particular, selective brain processes
which is still arriving over slowly con- the body sustains damage. The diver-
that exert control over the sensory in- ducting fibers or is being transmitted gence of afferent fibers going to the
put (Fig. 4). There are two known up more slowly conducting pathways. dorsal horns and the dorsal column
systems that could fulfill such a func- nuclei marks only the first stage of the
tion, and one or both may play a role. Action system. Pain is generally
considered to be the sensory adjunct process of selection and abstraction of
The first is the dorsal column- of an imperative protective reflex information. The stimulation of a sin-
medial lemniscus system. The largest (55). Pain, however, does not consist gle tooth results in the eventual acti-
and most rapidly conducting A fibers of a single ring of the appropriate vation of no less than five distinct
which enter the spinal cord send short central bell, but is an ongoing process. brain-stem pathways (58). Two of
branches to the substantia gelatinosa, We propose, then, that once the inte- these pathways project to cortical
and long central branches directly to grated firing-level of T cells exceeds a somatosensory areas I and II (59),
the dorsal column nuclei. Fibers from critical preset level, the firing triggers while the remainder activate the thal-
these nuclei form the medial lemniscus, a sequence of responses by the action amic reticular formation and the lim-
which provides a direct route to the system. bic system (60), so that the input has
thalamus and thence to the somato- Sudden, unexpected damage to the access to neural systems involved in
sensory cortex. The striking character- skin is followed by (i) a startle re- affective (54) as well as sensory ac-
istics of this system are that informa- sponse; (ii) a flexion reflex; (iii) tivities. It is presumed that interac-
tion is transmitted rapidly from the postural readjustment; (iv) vocaliza- tions occur among all these systems
skin to the cortex, that separation of tion; (v) orientation of the head and as the organism interacts with the en-
signals evoked by different stimulus eyes to examine the damaged area; vironment.
properties and precise somatotopic lo- (vi) autonomic responses; (vii) evo- We believe that the interactions be-
calization are both maintained through- cation of past experience in similar tween the gate control system and the
out the system (46), and that conduc- situations and prediction of the conse- action system described above may oc-
tion is relatively unaffected by anes- quences of the stimulation; (viii) many cur at successive synapses at any level
thetic drugs (47). Traditionally, the other patterns of behavior aimed at of the central nervous system in the
dorsal column system is supposed to diminishing the sensory and affective course of filtering of the sensory input.
976 SCIENCE, VOL. 150
Similarly, the influence of central ac- taneous activity, which would have the spread of pain, and trigger points at
tivities on the sensory input may take effect of keeping the gate open. Low- some distance from the original site
place at a series of levels. The gate level, random, ongoing activity would of body damage also point toward sum-
control system may be set and reset a then be transmitted relatively un- mation mechanisms, which can be un-
number of times as the temporal and checked (because of the predominant derstood in terms of the model. The
spatial patterning of the input is ana- loss of A fibers), and summation could T cell has a restricted receptive field
lyzed and acted on by the brain. occur, producing spontaneous pain in which dominates its "normal activi-
the absence of stimulation. This is a pos- ties." In addition, there is a wide-
sible mechanism for the pains of anes- spread, diffuse, monosynaptic input to
Adequacy of the Theory thesia dolorosa and the "spontaneous" the cell, which is revealed by electrical
pains which develop after peripheral- stimulation of distant afferents (41).
The concept of interacting gate con- nerve and dorsal-root lesions. Because We suggest that this diffuse input is
trol and action systems can account the total number of peripheral fibers normally inhibited by presynaptic gate
for the hyperalgesia, spontaneous is reduced, it may take considerable mechanisms, but may trigger firing in
pain, and long delays after stimulation time for the T cells to reach the firing the cell if the input is sufficiently in-
characteristic of pathological pain level necessary to trigger pain re- tense or if there is a change in gate
syndromes. The state of hyperalgesia sponses, so perception and response are activity. Because the cell remains dom-
would require two conditions: (i) delayed. This same mechanism can also inated by its receptive field, anesthesia
enough conducting peripheral axons account for post-ischemic pressure- of the area to which the pain is re-
to generate an input that can activate block hyperesthesia and for the delays ferred, from which only spontaneous
the action system (if, as in the case in sensation of as much as 10 seconds impulses are originating, is sufficient to
of leprosy, all components of the which occur when the large peripheral reduce the bombardment of the cell be-
peripheral nerve are equally affected, fibers fail to conduct (66). low the threshold level for pain. The
there is a gradual onset of anesthesia), We propose that the A-fiber input gate can also be opened by activities in
and (ii) a marked loss of the large normally acts to prevent summation distant body areas, since the substantia
peripheral nerve fibers, which may oc- from occurring. This would account gelatinosa at any level receives inputs
cur after traumatic peripheral-nerve for Adrian's (67) failure to obtain from both sides of the body and (by
lesions or in some of the neuropathies pain responses in the frog from high- way of Lissauer's tract) from the sub-
(61), such as post-herpetic neuralgia frequency air blasts which fired periph- stantia gelatinosa in neighboring body
(10). Since most of the larger fibers eral nerves close to their maximum fir- segments. Mechanisms such as these
are destroyed, the normal presynaptic ing rate, in an experiment meant to may explain the observations that stim-
inhibition of the input by the gate refute the view that summation of the ulation of trigger points on the chest
control system does not occur. Thus, effects of noxious stimuli is important and arms may trigger anginal pain
the input arriving over the remaining for pain. It is now clear that the air (70), or that pressing other body
myelinated and unmyelinated fibers is blasts would tend to fire a high pro- areas, such as the back of the head,
transmitted through the unchecked, portion of the low-threshold A fibers, may trigger pain in the phantom limb
open gate produced by the C-fiber in- which would exert presynaptic inhibi- (11).
put. tion on the input by way of the gate The sensory mechanisms alone fail
control system; thus the impulses to account for the fact that nerve le-
Spatial summation would easily oc-
would be prevented from reaching the sions do not always produce pain and
cur under such conditions. Any nerve
T cells where summation might occur. that, when they do, the pain is usually
impulses, no matter how they were
The double effect of an arriving vol- not continuous. We propose that the
generated, which converge on the cen-
ley is well illustrated by the effects of presence or absence of pain is deter-
tral cells would contribute to the out-
vibration on pain and itch. Vibration mined by the balance between the sen-
put of these cells. These mechanisms
activates fibers of all diameters, but sory and the central inputs to the gate
may account for the fact that non-
activates a larger proportion of A fi- control system. In addition to the sen-
noxious stimuli, such as gentle pres-
bers, since they tend to adapt during sory influences on the gate control sys-
sure, can trigger severe pain in patients
constant stimulation, whereas C-fiber tem, there is a tonic input to the sys-
suffering causalgia, phantom limb pain,
firing is maintained. Vibration there- tem from higher levels of the central
and the neuralgias. The well-known en-
fore sets the gate in a more closed po- nervous system which exerts an inhibi-
hancement of pain in these patients
sition. However, the same impulses tory effect on the sensory input (44,
during emotional disturbance and sex-
which set the gate also bombard the 71). Thus, any lesion that impairs the
ual excitement (62) might be due to
T cell and therefore summate with the normal downflow of impulses to the
increased sensory firing [as a result of
inputs from noxious stimulation. It is gate control system would open the
an increased sympathetic outflow (63,
observed behaviorally (26, 68) that vi- gate. Central nervous system lesions
64)] which is unchecked by presynaptic
bration reduces low-intensity, but en- associated with hyperalgesia and spon-
inhibition. Conversely, the absence of
hances high-intensity, pain and itch. taneous pain (7) could have this effect.
small fibers in the dorsal roots in a
Similar mechanisms may account for On the other hand, any central nerv-
patient with congenital insensitivity to
the fact that amputees sometimes ob- ous system condition that increases the
pain (65) suggests that the mecha-
tain relief from phantom limb pain by flow of descending impulses would tend
nisms for facilitation and summation
tapping the stump gently with a rub- to close the gate. Increased central fir-
necessary for pain may be absent.
ber mallet (69), whereas heavier pres- ing due to denervation supersensitivity
Spontaneous pain can also be ex- sure aggravates the pain (8). (72) might be one of these condi-
plained by these mechanisms. The tions. A peripheral nerve lesion, then,
smaller fibers show considerable spon- The phenomena of referred pain,
19 NOVEMBER 1965 977
system responsible for pain perception 27. P. D. Wall and A. Taub, J. Neurophysiol
would have the direct effect of open- 25, 110 (1962); L. Kruger and F. Michel
ing the gate, and the indirect effect, by and response is triggered after the cu- Exp. Neurol. S, 157 (1962).
28. G. F. Poggio and V. B. Mountcastle, Bull
increasing central firing and thereby in- taneous sensory input has been modu- Johns Hopkins Hasp. 106, 226 (1960).
creasing the tonic descending influences lated by both sensory feedback mech- 29. G. M. Kolmodin and C. R. Skoglund, Actc
Physiol. Scand. SO, 337 (1960); G. Gordon.
on the gate control system, of closing anisms and the influences of the cen- S. Landgren, W. A. Seed, / . Physiol. London
tral nervous system. We propose that 158, 544 (1960); J. S. Eisenman, S. Land-
the gate. The balance between sen- gren, D. Novin, Acta Physiol. Scand. Suppl
sory facilitation and central inhibition the abstraction of information at the 214, 1 (1963).
first synapse may mark only the be- 30. K. L. Casey, "A search for nociceptive ele-
of the input after peripheral-nerve le- ments in the thalamus of the awake squirrej
sion would account for the variability ginning of a continuing selection and monkey," paper read at the 16th Autumn
meeting of the American Physiological So-
of pain even in cases of severe lesion. filtering of the input. Perception and ciety, Providence, R.I., 1964.
The model suggests that psychologi- response involve classification of the 31. G. Weddell, Annu. Rev. Psychol. 6, 119
(1955).
cal factors such as past experience, at- multitude of patterns of nerve im- 32. D. H. Barron and B. H. C. Matthews, J,
tention, and emotion influence pain re- pulses arriving from the skin and are Physiol. London 92, 276 (1938).
33. D. O. Hebb, The Organization of Behavior
sponse and perception by acting on the functions of the capacity of the brain (Wiley, New York, 1949).
to select and to abstract from all the in- 34. R. W. Gerard, Anesthesiology 12, 1 (1951).
gate control system. The degree of cen- 35. T. Lewis, Pain (Macmillan, New York,
tral control, however, would be deter- formation it receives from the somes- 1942).
thetic system as a whole (7-9). A 36. G. H. Bishop, / . Nervous Mental Disease
mined, in part at least, by the tem- 128, 89 (1959).
poral-spatial properties of the input "modality" class such as "pain," which 37. P. D. Wall, Progr. Brain Res. 12, 92 (1964).
38. J. Szentagothai, J. Comp. Neurol. 122, 219
patterns. Some of the most unbearable is a linguistic label for a rich variety (1964).
pains, such as cardiac pain, rise so rap- of experiences and responses, repre- 39. P. D. Wall, / . Physiol. London 164, 508
(1963); L. M. Mendell and P. D. Wall, ibid.
idly in intensity that the patient is un- sents just such an abstraction from the 172, 274 (1964).
able to achieve any control over them. information that is sequentially re- 40. P. D. Wall, / . Neurophysiol. 22, 205 (1959);
J. Physiol. London 142, 1 (1958).
On the other hand, more slowly rising examined over long periods by the 41. L. M. Mendell and P. D. Wall, Nature 206
entire somesthetic system. 97 (1965).
temporal patterns are susceptible to 42. D. G. Whitlock and E. R. Perl, Exp. Neurol
central control and may allow the pa- 3, 240 (1961).
43. A. M. Halliday and R. Mingay, Quart. J.
tient to "think about something else" Exp. Psychol. 13, 1 (1961).
References and Notes 44. K. E. Hagbarth and D. I. B. Kerr, J.
or use other stratagems to keep the Neurophysiol. 17, 295 (1954).
pain under control (73). 1. K. M. Dailenbach, Amer. J. Psychol. 52, 331
(1939); K. D. Keele, Anatomies of Pain 45. H. G. J. M. Kuypers, W. R. Fleming, J. W.
(Blackwell, Oxford, 1957). Farinholt, Science 132, 38 (1960); A. Lund-
The therapeutic implications of the 2. W. H. Sweet, Handbook Physiol. 1, 459 berg, Progr. Brain Res. 12, 197 (1964).
46. V. B. Mountcastle, in Sensory Communica-
model are twofold. First, it suggests (1959).
tion, W. A. Rosenblith, Ed. (Massachusetts
3. D. C. Sinclair, Brain 78, 584 (1955).
that control of pain may be achieved 4. M. von Frey, Ber. Kgl. Sachs. Ges. Wiss. 46, Institute of Technology, Cambridge, 1961).
185 (1894); ibid., p. 283. 47. J. D. French, M. Verzeano, W. H. Magoun,
by selectively influencing the large, rap- 5. A. Goldscheider, Ueber den Schmerz in AM.A. Arch. Neurol. Psychiat. 69, 519
idly conducting fibers. The gate may physiologischer und klinischer Hinsicht (1953): F. P. Haugen and R. Melzack,
(Hirschwald, Berlin, 1894). Anesthesiology 18, 183 (1957).
be closed by decreasing the small-fiber 6. G. H. Bishop, Physiol. Rev. 26, 77 (1946); 48. T. C. Ruch and J. F. Fulton, Medical
Physiology and Biophysics (Saunders, Phila-
input and also by enhancing the large- A-delta fibers are the smallest myelinated
delphia, 1960).
fibers, C fibers are the unmyelinated fibers,
fiber input. Thus, Livingston (74) in peripheral nerve. 49. A. W. Cook and E. J. Browder Arch.
Neurol. 12, 72 (1965).
found that causalgia could be effective- 7. H. Head, Studies in Neurology (Keegan Paul,
50. F. Morin, Amer. J. Physiol. 183, 245 (1955).
London, 1920).
ly cured by therapy such as bathing 8. W. K. Livingston, Pain Mechanisms (Mac- 51. E. Oswaldo-Cruz and C. Kidd, J. Neuro-
physiol. 27, 1 (1964).
the limb in gently moving water, fol- milJan, New York, 1943).
52. U. Norrsell and P. Voerhoeve, Acta Physiol.
9. R. Melzack and P. D. Wall, Brain 85 331
lowed by massage, which would in- (1962). Scand. 54, 9 (1962).
10. W. Noordenbos, Pain (Elsevier, Amsterdam 53. C. S. Sherrington, in Textbook of Physiology,
crease the input in the large-fiber sys- 1959). E. A. Schafer, Ed. (Pentland, Edinburgh,
tem. Similarly, Trent (75) reports a 1900).
11. B. Cronholm, Acta Psychiat. Neurol. Scand.
Suppl. 72, 1 (1951). 54. J. V. Brady, Handbook Physiol. 3 1529
case of pain of central nervous system 12. W. K. Livingston, Sci. Amer. 88, 59 (1953);
(1960).
55. W. R. Hess, Diencephalon: Autonomic and
origin which could be brought under R. Melzack, ibid. 204, 41 (1961); T. X.
Extrapyramidal Functions (Grune, New York,
Barber, Psychol. Bull. 56, 430 (1959).
control when the patient tapped his 13. H. K. Beecher, Measurement of Subjective
1954).
56. J. M. R. Delgado, / . Neurophysiol. 18, 261
fingers on a hard surface. Conversely, Responses (Oxford Univ. Press, New York,
(1955); R. Melzack, W. A. Stotler, W. K.
1959).
any manipulation that cuts down the 14. W. Freeman and J. W. Watts, Psycho-
Livingston, ibid. 21, 353 (1958).
57. P. Schilder and E. Stengel, AM.A. Arch.
sensory input lessens the opportunity surgery in the Treatment of Mental Disorders
Neurol. Psychiat. 25, 598 (1931).
and Intractable Pain (Thomas, Springfield,
for summation and pain, within the III., 1950). 58. D. I. B. Kerr, F. P. Haugen, R. Melzack,
Amer. J. Physiol. 183, 253 (1955).
functional limits set by the opposing 15. I. P. Pavlov, Conditioned Reflexes (Milford,
59. R. Melzack and F. P. Haugen, ibid. 190,
Oxford, 1927).
roles of the large- and small-fiber sys- 16. , Lectures on Conditioned Reflexes 570 (1957).
(International Publishers, New York, 1928). 60. W. J. H. Nauta and H. G. J. M. Kuypers,
tems. Second, the model suggests that 17. J. P. Nafe, in Handbook of General Experi- in Reticular Formation of the Brain, H. H.
a better understanding of the pharma- mental Psychology, C. Murchison, Ed. (Clark Jasper et al., Eds. (Little, Brown, Boston,
Univ. Press, Worcester, Mass., 1934). 1958).
cology and physiology of the substan- 18. J. D. Hardy, H. G. Wolff, H. Goodell, Pain 61. W. Blackwood, W. H. McMenemey, A.
tia gelatinosa may lead to new ways Sensations and Reactions (Williams and Meyer, R. M. Norman, D. S. Russell, Green-
Wilkins, Baltimore, 1952). field's Neuropathology (Arnold, London,
of controlling pain. The resistance of 19. C. T. Morgan, Introduction to Psychology 1963).
62. W. R. Henderson and G. E. Smyth, / .
the substantia gelatinosa to nerve-cell (McGraw-Hill, New York, 1961).
Neurol. Neurosurg. Psychiat. 11, 88 (1948).
20. C. C. Hunt and A. K. Mclntyre, J. Physiol.
stains suggests that its chemistry differs London 153, 88, 99 (1960). 63. K. E. Chernetski, J. Neurophysiol. 27, 493
21. J. Maruhashi, K. Mizaguchi, I. Tasaki, ibid. (1964).
from that of other neural tissue. Drugs 117, 129 (1952). 64. J. Doupe. C. H. Cullen, G. Q. Chance, / .
affecting excitation or inhibition of sub- 22. W. W. Douglas and J. M. Ritchie, ibid. Neurol. Neurosurg. Psychiat. 7, 33 (1944).
139, 385 (1957). 65. A. G. Swanson, G. C. Buchan, E. C. Alvord,
stantia gelatinosa activity may be of 23. A. Iggo, ibid. 143, 47 (1958). Arch. Neurol. 12, 12 (1965).
particular importance in future at- 24. P. D. Wall, / . Neurophysiol. 23, 197 (1960). 66. D. C. Sinclair and J. R. Hinshaw, Brain 74,
25. V. H. Mark, F. R. Ervin, P. I. Yakovlev, 318 (1951)
tempts to control pain. Arch. Neurol. 8, 528 (1963). 67. E. D. Adrian, The Basis of Sensation: The
26. P. D. Wall and J. R. Cronly-Dillon, ibid. Action of Sense Organs (Christophers, Lon-
The model suggests that the action 2, 365 (1960). don, 1928).