In his thoughtful review [1], Dr. Macionis identifies to some extent problems arising from the uncritical clinical acceptance of the construct of “nociplastic pain” which, he emphasises, is “a mechanism of pain rather than a diagnosis”. We agree that “nociplastic pain” is not a diagnosis, just as “nociceptive” and “neuropathic” pain are not diagnoses, according to the IASP terminology [2].

But Dr. Macionis’ point highlights the misconception of these “mechanistic descriptors of pain”, often called “pain descriptors”. Both terms are misnomers, as they refer to hypotheses of the activation of nociception [3], which is necessary but not sufficient for the experience of pain [4]. Nociception and pain are different phenomena and must not be conflated.

Possibly inadvertently, Dr. Macionis also repeats the conflation of “nociplastic pain,” “chronic pain,” and “nociceptive central sensitization” that is found in the literature, even though the first is a hypothesis of activation of nociception, the second is a taxonomic concept, and the third (also termed “central sensitization of nociception”) is a neurophysiological process.

It is true, as Dr. Macionis asserts, that the underlying pathophysiology of nociplastic pain is speculative at this time. However, his characterization of it as “spontanenous activity (firing) of neurons” is incomplete, as the phenomenon of “neural sensitization” includes a prolonged but reversible increase in the excitability and synaptic efficacy, in this case of neurons in central nociceptive pathways [5]. In this context, recognition and dissection of the clinical phenomenon of allodynia is integral to the appreciation of nociplastic pain.

Dr. Macionis incorrectly asserts that the definition of nociplastic pain (which admittedly is clumsy) implies “alteration (or malfunction) of nociceptors” when, in fact, it invokes “altered nociception” [6], which, as has been argued, should refer to a broader nociceptive apparatus [3].

Dr. Macionis’ argument then rapidly turns to the search for “a persistence of organic pathology that eludes diagnosis but can drive central sensitization” or “a periodic rekindling of latent sensitization via the alternating activity of some background organic condition” such as an “occult neuropathy”. His concept of “latent sensitization” recalls that of “latent trigger points”. Indeed, Dr. Macionis does appear enamoured of myofascial pain theory, a construct that has not withstood critical analysis [7,8]. In any event, his hypothesis that “occult, currently undetectable, conditions associated with neural damage may explain nociplastic pain” is inherently untestable and, as such, can be dismissed.

Very surprisingly to us, Dr. Macionis then veers into discredited territory, to include the nebulous concepts of psychogenic (somatoform) pain and pure emotional (psychological) pain under the banner of nociplastic pain. Where is the evidence for “psyche-driven sensitization”? Here, he invokes the fallacious concept of pain as a “thing” by stating that “...sensitization (neural hypersensitivity) can be caused (sic) both by psychogenic and by emotional pain”. Pain, as an experience, has no agentive properties [9], while “emotional pain” is a metaphor for suffering, as distinct from the experience of pain [10].

The ”nociplastic pain” construct arose out of clinical need [6]. Although it is based on careful clinical observation and sound theoretical foundations, it remains a placeholder concept until its underlying pathophysiological bases–in humans–are elucidated. Of course, it is not a diagnosis, any more than “chronic pain” or “pain” itself were ever “diagnoses”, but it has opened up a conversation about nociception and its conflation with pain at a fundamental level, while providing clinical legitimacy if not also preventing harm, rather than “weaken[ing] diagnostic alertness”.