Classification of primary headaches: pathophysiology versus nosology?
The classifications of primary headache disorders, both the 1988
version and its revision in 2004, are purely phenomenological exercises
without any pathophysiological basis.1 The acknowledgement of critical
limitations of primary headache nosology 2 carries no inkling of the
mutually opposing influences of nosological sophistication and evolution
of pathophysiology.3 Identification of narrow homogenous groups can
actually impede the creation of an overarching comprehensive
pathophysiological system.
No pathophysiological insight about "transforming" primary headaches
devolves from the new version of classification. The pathogenetic
mechanism(s) of rather semantic subtypes of migraine or tension-type
headache cannot be as diverse as the classification itself, which
reservation underscores a substantial degree of artificial individuality
to the entities (episodic tension-type headache, chronic tension-type
headache, other tension-type headaches, transformed migraine, chronic
daily headache or chronic migraine) created primarily on the basis of
frequency of head pain.1 The basis of the concept of analgesic-associated
headache is a vague mass of suppositions; we know of no central neuronal
process possibly relevant to migraine pathophysiology that might be
affected by chronic analgesic consumption.2 Today, migraine research
stands where ischemic heart disease stood before the discovery of the
atheromatous plaque, when every variant of anginal chest pain could be
touted as a new clinically important variant or subtype.
Experimental and therapeutic studies in migraine, stimulated by
nosological sophistication, have circumvented the formidable challenges of
the basic sciences involved. Only with such a clinical-research disconnect
might one maintain the hope, as expressed,2 that pathophysiological,
genetic, or therapeutic evidences may further fragment the already
somewhat cumbersome classification. Anatomically, no bioclinical correlate
is more important than the characteristic lateralization of headache,
unilateral, bilateral or side-shifting. Simply because the physico-
chemical substrate / idiosyncracy responsible for lateralizing headache
has not yet been detected, it does not mean that it is not important.
Migraine researchers have attempted to attenuate the anatomical importance
of lateralizing headache by implicating midline-crossing pontine neuronal
interconnections, a theory that challenges fundamental neuroanatomical
concepts.4 Physiologically, post-stress headache is the vital clue that
will establish the conceptual divide between pathogenetic and adaptive
physiological events that push the patient towards headache or headache-
free state, respectively. The primary pathogenetic system in migraine is
afforded a considerable but eventually exhaustible protection during
stress. While we do not fully understand post-stress headache, the
proposal for a neuroendocrine "system" that maintains vascular integrity,
antinociception, and behaviour control is a first step in this direction.5
Pharmacologically, two key issues are considered unimportant by headache
researchers: (i) Atenolol, a first line prophylactic evaluated in three
well-controlled trials as well as mentioned in several critical reviews,
does not freely cross the blood-brain barrier (BBB). The ability of
prophylactic agents to cross BBB is critical in influencing brain neuronal
function.4 (ii) Both serotonin antagonists and agonists prevent migraine.
Amitriptyline, a well proven prophylactic agent,6 is unambiguously
regarded as a brain serotonin agonist, except in the field of primary
headache research. Amitriptyline remains uncertainly grouped with other
proven prophylactic agents.6
Till basic science issues surrounding primary headache
pathophysiology remain peripheral, no meaningful biological advance will
be achieved. Taxonomic sophistication is working against basic sciences in
migraine research.7
References
1. Gupta VK. De novo headache and analgesic consumption:
pathophysiological insights from nosologic complexity? Headache 2004 (In
press, April issue).
2. Peatfield R. A revised classification of headache disorders. BMJ
2004;328: 119-20.
3. van Pragg HM, Lader MH, Rafaelsen OJ, Sachar EJ. Handbook of
Biological Psychiatry. New York: Marcel Dekker, INC, 1979.
4. Gupta VK. Migraine following haemorrhage in brain stem cavernous
angioma: pathophysiological considerations. Published electronic response
to Afridi S, Goadsby PJ. New onset migraine with a brain stem cavernous
angioma. J Neurol Neurosurg Psychiatry 2003;74: 680-1.
5. Gupta VK. A clinical review of the adaptive role of vasopressin in
migraine. Cephalalgia 1997:17: 561-9.
6. Goadsby PJ, Lipton RB, Ferrari MD. Migraine – current understanding and
treatment. N Engl J Med 2002;346: 257-70.
7. Gupta VK. Menstrual migraine is not pathogenetically related to
premenstrual syndrome. Cephalalgia 1994;14: 411-14.
Competing interests:
None declared
Competing interests:
No competing interests
22 January 2004
Vinod K Gupta
Physician
Dubai Police Medical Services, P. Box 12005, Dubai, United Arab Emirates
Rapid Response:
Classification of primary headaches: pathophysiology versus nosology?
The classifications of primary headache disorders, both the 1988
version and its revision in 2004, are purely phenomenological exercises
without any pathophysiological basis.1 The acknowledgement of critical
limitations of primary headache nosology 2 carries no inkling of the
mutually opposing influences of nosological sophistication and evolution
of pathophysiology.3 Identification of narrow homogenous groups can
actually impede the creation of an overarching comprehensive
pathophysiological system.
No pathophysiological insight about "transforming" primary headaches
devolves from the new version of classification. The pathogenetic
mechanism(s) of rather semantic subtypes of migraine or tension-type
headache cannot be as diverse as the classification itself, which
reservation underscores a substantial degree of artificial individuality
to the entities (episodic tension-type headache, chronic tension-type
headache, other tension-type headaches, transformed migraine, chronic
daily headache or chronic migraine) created primarily on the basis of
frequency of head pain.1 The basis of the concept of analgesic-associated
headache is a vague mass of suppositions; we know of no central neuronal
process possibly relevant to migraine pathophysiology that might be
affected by chronic analgesic consumption.2 Today, migraine research
stands where ischemic heart disease stood before the discovery of the
atheromatous plaque, when every variant of anginal chest pain could be
touted as a new clinically important variant or subtype.
Experimental and therapeutic studies in migraine, stimulated by
nosological sophistication, have circumvented the formidable challenges of
the basic sciences involved. Only with such a clinical-research disconnect
might one maintain the hope, as expressed,2 that pathophysiological,
genetic, or therapeutic evidences may further fragment the already
somewhat cumbersome classification. Anatomically, no bioclinical correlate
is more important than the characteristic lateralization of headache,
unilateral, bilateral or side-shifting. Simply because the physico-
chemical substrate / idiosyncracy responsible for lateralizing headache
has not yet been detected, it does not mean that it is not important.
Migraine researchers have attempted to attenuate the anatomical importance
of lateralizing headache by implicating midline-crossing pontine neuronal
interconnections, a theory that challenges fundamental neuroanatomical
concepts.4 Physiologically, post-stress headache is the vital clue that
will establish the conceptual divide between pathogenetic and adaptive
physiological events that push the patient towards headache or headache-
free state, respectively. The primary pathogenetic system in migraine is
afforded a considerable but eventually exhaustible protection during
stress. While we do not fully understand post-stress headache, the
proposal for a neuroendocrine "system" that maintains vascular integrity,
antinociception, and behaviour control is a first step in this direction.5
Pharmacologically, two key issues are considered unimportant by headache
researchers: (i) Atenolol, a first line prophylactic evaluated in three
well-controlled trials as well as mentioned in several critical reviews,
does not freely cross the blood-brain barrier (BBB). The ability of
prophylactic agents to cross BBB is critical in influencing brain neuronal
function.4 (ii) Both serotonin antagonists and agonists prevent migraine.
Amitriptyline, a well proven prophylactic agent,6 is unambiguously
regarded as a brain serotonin agonist, except in the field of primary
headache research. Amitriptyline remains uncertainly grouped with other
proven prophylactic agents.6
Till basic science issues surrounding primary headache
pathophysiology remain peripheral, no meaningful biological advance will
be achieved. Taxonomic sophistication is working against basic sciences in
migraine research.7
References
1. Gupta VK. De novo headache and analgesic consumption:
pathophysiological insights from nosologic complexity? Headache 2004 (In
press, April issue).
2. Peatfield R. A revised classification of headache disorders. BMJ
2004;328: 119-20.
3. van Pragg HM, Lader MH, Rafaelsen OJ, Sachar EJ. Handbook of
Biological Psychiatry. New York: Marcel Dekker, INC, 1979.
4. Gupta VK. Migraine following haemorrhage in brain stem cavernous
angioma: pathophysiological considerations. Published electronic response
to Afridi S, Goadsby PJ. New onset migraine with a brain stem cavernous
angioma. J Neurol Neurosurg Psychiatry 2003;74: 680-1.
5. Gupta VK. A clinical review of the adaptive role of vasopressin in
migraine. Cephalalgia 1997:17: 561-9.
6. Goadsby PJ, Lipton RB, Ferrari MD. Migraine – current understanding and
treatment. N Engl J Med 2002;346: 257-70.
7. Gupta VK. Menstrual migraine is not pathogenetically related to
premenstrual syndrome. Cephalalgia 1994;14: 411-14.
Competing interests:
None declared
Competing interests: No competing interests