Here, I briefly respond to Robinson, Staud and Price6 concerning what constitutes the ‘neural signature’ of pain (p. 325), note a logical mistake in their article, and highlight a reason why explaining pain is difficult. It is probable that conscious pain may be subserved by an unconscious physical base with a specific neurophysiological signature. Explaining pain in this direct way aims first to describe the base as a correlate of pain, then ultimately to achieve a reductive neurophysiological explanation of pain. Multiple evidential lines demonstrate that the neurophysiological base of pain need not be limited to one physical location, as Robinson, Staud and Price rightly note (p. 325). Since the hypothetical pain base is probably distributed, and therefore is more akin to the immune system than the liver, it is mistaken to expect that if it is not confined to a single neural region, or a single pattern of functional interaction, then there cannot be a physical signature of pain, as Robinson, Staud and Price appear to think (p. 325). Instead of a region-based view of the hypothetical pain base, it may be more accurate to think of it as a distributed mechanism.5, 8

The mechanism of pain could involve any number of neurophysiological systems (nervous, endocrine, immune), or reciprocal interactions between them, or any number of neurophysiological levels (pathway, network, single cell, molecular), or reciprocal interactions between them.1, 7, 8 The probability of a distributed mechanism, combined with the open-ended probability concerning the systems and level at which the mechanism exists, explains why current hypotheses and theories of pain in the literature, including those made in the article by Robinson, Staud and Price, are relatively unconstrained. However, the absence of constraints is not indicative of the likely truth of Cartesian dualism, the futility of searching for neurophysiological pain correlates, or the unreliability of verbal pain self-report. Rather, it indicates that pain science has much to do.

Neurophysiological mechanism and pain experiences can be correlated for a variety of reasons: the mechanism is part of the cause of pain; the mechanism is part of the effect of pain; the mechanism indirectly parallels pain; the mechanism is what pain can be identified with.2, 8 Discovering the neurophysiological signature of pain requires the identification of some neurophysiological mechanism with pain. The correlation of mechanism x with pain is informative because x may be the one for identifying pain. Correspondingly, mechanism y that does not correlate with pain indicates that y may not be the one. If there is a pain mechanism with a neurophysiological signature identifiable with pain experiences, the scientific and clinical benefits could be huge. Thus, investigating pain directly is worth a try.

Now, it is quite possible that a scientist may be looking at an instance of the pain signature without comprehending that it is an instance. This will occur if the physical base of pain does not possess an identifying property that is obvious to naïve researchers, but is comprehensible only through the availability of a more complete general theory of brain function.2, 3, 4, 8 The limitations in explaining pain are not simply technological. After all, how would a person know, independently of Antoine Lavoisier’s studies on oxygen, that metabolizing, burning and rusting are identical with the same mechanism, but that lightning and sunlight are not? Thus, Robinson, Staud and Price are right in asserting that it is misconceived to replace pain ratings with neuroimaging data, especially at this early stage of pain investigations.


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