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Neuropathic Pain: A Crisis of Definition?

2003; Lippincott Williams & Wilkins; Linguagem: Inglês

10.1213/01.ane.0000081724.18956.d9

1526-7598

Gary J. Bennett,

Musculoskeletal pain and rehabilitation

To provide a definition means to state the essential qualities of something. A definition is not quite the same thing as a diagnosis, which is the art of identifying a disease from its signs and symptoms. The signs and symptoms that characterize a disease are not necessarily its essential qualities. It is thus possible to diagnose a condition with a high degree of certainty without being able to give it a satisfactory definition; indeed, until a couple of centuries ago this was the rule, and in our own time it is far from rare. Neuropathic pain is a case in point. The introduction during the past two decades of animal models of posttraumatic and diabetic painful peripheral neuropathies has produced an enormous literature on possible pathogenic mechanisms, but, to my mind at least, it is still not possible to state the essential qualities of neuropathic pain. And diagnosis is still sometimes problematical, especially in cases where there are symptoms but no visible signs of damage to the nervous system, most notably complex regional pain syndrome (CRPS) type I (reflex sympathetic dystrophy), fibromyalgia, irritable bowel syndrome, and many cases of chronic low back pain. The International Association for the Study of Pain (IASP) defines neuropathic pain as being caused by a lesion or dysfunction of the nervous system. This definition has been criticized often, most frequently for the conceptual vagueness of “dysfunction.” I would stress that there is also an obvious problem with “lesion”: a very large majority of lesions to the nervous system (diabetes, herpes zoster, trauma, etc.) do not give rise to neuropathic pain. In this issue, Professor Backonja (1) calls attention to the growing concern that we face a crisis of definition and diagnosis of neuropathic pain. This is manifest by several recent articles decrying the use of neuropathic pain as a catchall diagnostic category. He suggests for our consideration and discussion a new definition of neuropathic pain, and he introduces a new category, “hypersensitivity pain disorder.” Is there really a crisis of definition or diagnosis? To my mind there is no crisis, just the usual frustrating muddle. Learned papers cannot help us here; what we need is more knowledge. Meanwhile, both basic researchers and clinicians have no choice but to carry on—in the frank cognizance of the limitations of our current knowledge and with determination to try to do something about it. I see no reason for pessimism. We have learned more about neuropathic pain in just the past decade than in all the centuries that have gone before. We have identified several new classes of drug, and some patients (regrettably not all) are obtaining relief that could not be offered before. Refinement of diagnosis continues: witness the realization that there are significant subtypes of postherpetic neuralgia, and the hypothesis that different symptoms (e.g., dynamic mechanoallodynia and paroxysmal spontaneous pain) may have different causes and require different therapies. Does the inclusion of, for example, irritable bowel syndrome, in the category of neuropathic pain do any harm? I doubt it. It seems to me that the worst that could happen is that the patient might receive a trial of gabapentin (which, for all we know, might work). Where does this sense of crisis come from? I think it is likely that the frustrating muddle is more frustrating than before. At a basic level, our knowledge is growing very rapidly. But progress has been much slower at the clinical level. Many have a profound distrust of a diagnosis based on symptoms alone when the symptom is pain, and basic research has not uncovered a test that would yield an unequivocal sign. Perhaps most importantly, the rush of basic science results has been slow to result in improved therapy (with the obvious exception of the discovery of efficacy among the new antiepileptic drugs). No one is at fault here; the animal models have shown us where efficacy lies, but Nature has made it very hard to find a well-tolerated N-methyl-d-aspartic acid receptor antagonist, N-type calcium channel blocker, or sodium channel blocker. Shall we accept a new definition—“neuropathic pain is due to disease or injury of the thermonociceptive component of the nervous system?” This is an attractive and testable hypothesis. It is consistent with the currently accepted definition of the central pain syndrome, extending the idea from thermonociceptive regions of the central nervous system to include the thermonociceptive primary afferent neurons, and it is consistent with a growing body of evidence that damage to unmyelinated and small myelinated primary afferent axons is somehow key to the genesis of neuropathic pain. But it seems to me to be very premature as a definition when the injury or disease is in the peripheral nervous system, and it does not address the problem of what constitutes the essential pain-evoking component of the injury or disease. Would it be useful to have a better definition of neuropathic pain? Of course it would, but I do not think we have the knowledge to improve upon the IASP definition. Shall we accept a new category of pain — “hypersensitivity pain disorder”? The purpose of the new category is to remove “dysfunction” from the main definition, and to place problematic diagnoses (CRPS-I, fibromyalgia, irritable bowel syndrome) in a separate category—a category for conditions where we presume that our knowledge of pain mechanisms is even poorer than it is for cases where there is a visible lesion of the nervous system. I see little logic in this proposal. First, why should conditions with a visible lesion of the nervous system be accorded special status when the lesion (as we know it today) tells us nothing about why there is pain? Second, why discard “dysfunction”? Congenital epilepsy and schizophrenia are reasonable diagnostic categories characterized by obvious dysfunction without a known lesion. Until just a few decades ago, Parkinson’s disease was defined as a dysfunction of the extrapyramidal motor system. Now we know the lesion—the death of dopaminergic neurons in the substantia nigra. One can hope that pain conditions (CRPS-I, fibromyalgia, etc.) now classified as dysfunctional states of the pain-sensing system (a concept no vaguer than “dysfunction of the extrapyramidal motor system”) will one day have their respective lesions identified. Until they do, why separate (and, I fear, stigmatize) them? Pain research is one of the most exciting and productive areas in neuroscience. New facts are accumulating rapidly. There are many examples in the history of science where the accumulation of facts raced ahead of an increase in real understanding and ahead of practical applications. That is where we are now. The key insights will come. Better therapy will come. Be patient and work hard.