Wednesday, February 05, 2014

What Patrick Wall said about the relationship of nociception and pain

I am looking at a paper Patrick D Wall wrote with SB McMahon:

... published in Trends in Neuroscience in 1986. 

(Gee, that doesn't feel like almost 30 years ago. Time sure flies by.) 


In paragraph 1, the authors say this:

"The word nociceptor is a purely physiological term meaning fibre that responds to stimuli that damage tissue or would damage tissue if they were prolonged. The word pain is a purely psychological term defined as 'an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage'. What then is the relation between the physiological existence of impulses in nociceptors and the psychological response? For visceral pain, the question may not even arise, since the existence of specific visceral nociceptors is strongly doubted. But nonetheless, most textbooks of physiology and neurology imply that pain is a unique consequence of impulses in nociceptors by referring to pain fibres, pain cells and pain tracts. For instance, a recent text specializing in neuroscience states 'primary pain afferents terminate in the dorsal horn of the spinal cord', and 'the pain projection pathways are collectively called the anterolateral system'."

My bold. The reference for that is none other than Kandel, E. R. and Schwarz, J. H. (eds) (1985) Principles of Neural Science, 2nd edn, Elsevier. It's a classic. Anyone who wants to know anything about neuroscience has this big thick book on their shelf. I have the 4th edition. It is a good three inches thick and filled with wonderfulness. I don't have the latest 5th edition - something might have changed, but generally what Wall and McMahon said is true - people who write textbooks make that same sloppy error, over and over. 

In the second paragraph the authors refer to Hagbarth and Vallbo, two Swedes who developed single afferent nerve fibre recording in humans in 1968, direct comparisons they made of sensation with primary afferent discharge patterns. 

They say:

"For cutaneous sensations, the results do not support the classical view, which is still adopted by so many. Rather they demonstrate that the threshold, intensity, quality, time course and location of perceived pain is determined by central mechanisms that take into account several specifiable factors in addition to the firing of nociceptors. This article will consider these factors in some detail."

Right there is a good reason to do human primate social grooming - persuade the brain at the other end of those neurons to change its mind about how the world "feels" to it. But I digress. For more about microneurography, you can check out these cited references: Hagbarth, K. E. and Vallbo, A. B. (1968) Exp. Neurol. 22, 674-694, and Vallbo, A. B. and Hagbarth, K. E. (1968) Exp. Neurol. 21, 270-289. 

Wall and McMahon go on about very specific advanced (in the day) microneurography technique "in which they pass current through their recording electrodes and claim to stimulate the same fibre that they had been recording from, and that fibre only." And they cite:  
Schady, W. J. L., Torebjörk, H. E. and Ochoa, J. L. (1983) Brain Res. 277, 249-261 5
Torebjörk, H. E. and Ochoa, J. L. (1980) Acta Physiol. Scand. 110, 445--447 6
Vallbo, A. B. (1976)Acta Physiol. Scand. 97, 66-74 7
Vallbo, A. B. (1981)Brain Res. 215,359-363 8
Vallbo, A. B., Olsson, K. A., Westberg, K-G. and Clark, F. J. (1984) Brain 107,727-740
They continue describing how this approach has been used for a range of tactile cutaneous afferents, how this has led the researchers to conclude that "activation of a single afferent nerve fibre gives rise to a sensation that corresponds to the properties of the receptive field of the fibre." That "these findings endorse the concept that the quality of sensation is coded in specific sensory systems", that "they provide novel evidence that sensory quality, magnitude and localization can be exquisitely resolved at cognitive levels on the basis of input initiated in a single mechanoreceptor unit." The reference provided is Ochoa, J. and Torebjörk, E. (1983) J. Physiol. (London) 342, 633-654.

Apparently Wall and McMahon must have protested the neatness and tidiness and conclusiveness of all this: the arguments they mounted are "fully discussed elsewhere" in Wall, P. D. and McMahon, S. B. (1985)Pain 21, 209-229.

They continue:
"Here we wish only to point out that there are objections to these conclusions and to correct any impression that the work supports the notion that pain is the equivalent of afferent nociceptor discharge. In fact, even the microneuronographers themselves do not make the same claims for pain as they do for touch, although it is easy to see how their general conclusions regarding cutaneous sensibility might be taken to apply to pain."

A bunch of technical stuff follows: tungsten electrodes, who was who and who did what. Comments are made about how the size of the electrode is the same as that of the axon being tested. They remark, "The most likely explanation of these single unit recordings is that the presence of the electrode and its manipulation induces a pressure block of the majority of the nearby fibres allowing only one or a few axons to conduct impulses into the region of the recording tip."

Details reside in  
Hallin, R. G. and Torebjörk, H. E. (1970) Acta Soc. Med. Ups. 75, 277-281
Torebjörk, H. E. and Hallin, R. G. (1970) Acta Soc. Med. Ups. 75, 81-84
Van Hees, H. and Gybels, J. M. (1972) Brain Res. 48, 397-400

Then the discussion turns to A deltas and Cs:
Hallin, R. G. and Torebjörk, H. E. (1970) Acta Soc. Med. Ups. 75, 277-281
Torebjörk, H. E. and Hallin, R. G. (1970) Acta Soc. Med. Ups. 75, 81-84
Van Hees, H. and Gybels, J. M. (1972)Brain Res. 48, 397-400
Gybels, J., Handwerker, H. O. and van Hees, J. (1979) J. PhysioL (London) 292, 193-206
They continue: 
"It might be expected that the onset of firing of one of these types of fibre would invariably coincide with the onset of pain, but this has not been observed. Both groups of fibres begin to respond to pressure or chemicals or heat at stimulus intensities well below those that evoke pain. To take C fibres responding to heat as an example, most fibres begin responding at 41°C while the pain threshold can be as high as 49°C. In this study, the authors conclude that central spatial summation from many nociceptors is necessary before pain is sensed (Torebjörk, H. E., La Motte, R.H. and Robinson, C. J. (1984) J. Neurophysiol. 51, 325-339). Another group show that 'subjective ratings give a better estimation of stimulus size than did the discharge rates of the individual C fibres' (Gybels, J., Handwerker, H. O. and van Hees, J. (1979) J. PhysioL (London) 292, 193-206).
It is apparent that the ability to establish a threshold and to estimate intensity is not determined by the properties of single peripheral fibres or even types of peripheral fibre. Rather the periphery feeds information that is then interpreted in terms of threshold and intensity by central structures."

See what they did? They spotted an inconsistency in the work itself, an oversight, a contradiction between what was actually stated, and how most people went on to blithely interpret it. Then they pointed it out, in writing.

They go on about that for awhile longer, point out how subjects can't tell the difference between hot punctate stimulus or just punctate pressure, how much of a difference there is in pain threshold: "The C fibre firing rate when the stimulus becomes painful is 0.5 Hz for the heat stimulus and over 10 Hz for the pressure stimulus." How the difference is predicted by gate control theory, explained by the fact that pressure stimulus activates both high and low threshold fibres, that low threshold fibres exert inhibition over central excitation produced by small afferents (Melzack, R. and Wall, P. D. (1962)Brain 85, 331-356). How a larger afferent barrage is required in small fibres to produce the same central effect if large fibres are being stimulated at the same time. How this reflects the way the CNS responds to combinations of inputs from many different fibre types. This sort of reflection continues for a good length of time in the paper with minute detail about pain thresholds, size of area being stimulated, what size probe results in what sort of perceived sensation. 
"This evidence shows that the CNS is analysing modality and intensity not only on the basis of firing frequency in particular afferents but also by taking into account the spatial gradient of the stimulus. This contradicts the classical view that modality is determined by the activation of modality-labelled specific fibres that end in local skin spots. Spot-like variations in sensitivity exist but they cannot be attributed to the local presence of special nerve fibres for the following reasons. The spots rapidly move, appear and coalesce. They are not associated with particular types of ending. There are far more endings than spots. The size of the spot depends on the size of the stimulus (Melzack, R. and Wall, P. D. (1962) Brain 85, 331-356; Boring, E.G.(1942) Sensation and Perception in the History of Experimental Psychology, Appleton-Century-Crofts; Johansson, R. S. and Vallbo, A. B. (1979) J. Physiol. (London) 286, 283-300; Johansson, R. S. and Vallbo, A. B. (1976) in Sensory Functions of the Skin in Primates (Zotterman, Y ., ed.), pp. 171-184, Pergamon Press).
"These facts require that the central processing of the afferent barrage take into account which groups of fibres are responding, what is their relative frequency of discharge, and what is the spatial gradient of responding fibres."
Then more technical detail about A deltas and Cs.
Then,  "It is evident that the time course of sensation is determined by central factors other than the arrival of the afferent barrage (Vallbo, A. B. and Johansson, R. S. (1976) in Sensory Functions of the Skin in Primates (Zotterman, Y., ed.), pp. 185-199, Pergamon Press)."

This is true. So very true. Which is why we human primate social groomers need to be careful with our handling. 

They go on about what sort of subjects volunteer for such experiments, and comment that "It is not surprising that the slings and arrows of of the real world produce pain by mechanisms that require more factors for their explanation than the firing of a specific type of afferent. At one extreme, 90% of patients with brachial root avulsions suffer severe pain in the absence of afferents let alone impulses in afferents. At the other extreme, 40% of patients admitted to a civil accident hospital suffered no pain at the time of their injury in spite of being fully aware that they were severely injured. Between these extremes, pain is perceived in terms of injury in the context of the afferent barrage in nociceptors and of other afferents and of analytic processes in the brain."

My mind drifts back to Kevin Ware, who swore he felt no pain when his leg broke and he collapsed on the basketball court last spring, his tibia sticking out a good three inches beyond the skin it tore through, leg bent at a crazy angle, foot dangling helplessly; I am reminded of the guy who suffered acute agony in a construction injury, wouldn't let anyone touch him or the boot from which protruded a large spike, until he was give a big dose of pain meds, but when the boot was removed, it turned out the spike had only pierced the boot, not the foot. 

Wall and McMahon conclude,
"The awareness of touch by itself may be a neutral event without implicit meaning. The labelling of nociceptors as pain fibres was not an admirable simplification but an unfortunate trivialization. The writers of textbooks will continue to purvey trivialization under the guise of simplification. The experimental results show that the final analysis that produces the perception of pain is not monopolized by the peripheral receptor properties of nociceptors. The response of nociceptors is one of the factors incorporated into the central analytic mechanisms that can generate many perceptual syndromes including pain."
My bolds. 
Life grinds on. 
The 'unfortunate trivialization' continues. 

Patrick Wall

By Sigurd Mikkelsen, Norwegian PT

Mechanisms of Pain, Chapter 2 in Recognition and Alleviation of Pain in Laboratory Animals. Very clear straightforward elucidation of the difference between pain and nociception.