572 J Neurol Neurosurg Psychiatry 2005;76:572

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.2004.047381 on 16 March 2005. Downloaded from http://jnnp.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
HISTORICAL NOTE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
doi: 10.1136/jnnp.2004.047381
Post herpetic neuralgia
The herpes virus colleagues carried out extensive pathological studies of nerve
In Romeo and Juliet (I.iv), Shakespeare gives a possible root and dorsal ganglion and cord.9 In four post-herpetic
description of herpes simplex: neuralgia cases, shrinkage of the ipsilateral dorsal horn was
combined with loss of DRG neurones and peripheral large
‘‘O’er ladies’ lips, who straight on kisses dream; myelinated axons. However, one of the cases without PHN
Which oft the angry Mab with blisters plagues.’’ had an ipsilateral myelopathy with loss of myelinated axons
indistinguishable from chronic post-herpetic neuralgia.10
William Heberden distinguished chickenpox from small-
Thus, there was no specific pathology to correlate with the
pox in 1767 in a report to the Royal College of Physicians. In
presence or absence of neuralgia.
1875 Steiner transmitted varicella to children by inoculating
fluid from the vesicles of chickenpox patients, thus establish- Noordenbos, in 1959, using intercostal nerve biopsies
ing its infectious nature. showed a reduction of large diameter myelinated fibres and
James Von Bokay in 18921 first questioned: proposed that the predominant loss of large myelinated
afferents leads to a loss of their central inhibitory effects on
‘‘whether or not the unknown infectious material of pain produced by small diameter C-fibre nociceptive affer-
chickenpox could under certain circumstances manifest ents.11 Noordenbos’s hypothesis of the unrestrained effects of
itself instead as a zoster eruption.’’ C-fibre input into the cord became influential in Melzack and
Wall’s gate control hypothesis.12
In 1904 Ernest Tyzzer studied epidemics in a Philippines Patients with post-herpetic neuralgia are classified into:
prison; he concluded that smallpox and chickenpox were (1) an irritable nociceptor group with minimal deafferenta-
different illnesses and proved that they could be separated by tion and touch evoked allodynia owing to peripheral
microscopy of skin biopsies (where he saw large multi- nociceptor input; (2) a deafferentation group with marked
nucleated cells in varicella but not in smallpox). In 1925 sensory loss and no allodynia; and (3) a deafferentation
Kundratitz demonstrated that vesicular fluid from zoster group with sensory loss and allodynia owing to central
patients could produce varicella when inoculated into reorganisation. Post-herpetic neuralgia correlates with allo-
susceptible children. In 1948 the virus was revealed by dynia and altered sensory thresholds to several modalities.
electron microscopy. The isolation of the virus from zoster Somatotopic remodelling or central sensory reorganisation13
and varicella patients was the work of Weller and Stoddard2 are the words often applied to the creation of pain: though
in 1952 and that the same virus was common to both words of conjecture they remain.
diseases was recognised by Weller et al in 1958. Hope-
Simpson deduced that herpes zoster was caused by reactiva- J M S Pearce
tion of dormant varicella-zoster virus. 304 Beverley Road, Anlaby, East Yorkshire HU10 7BG, UK;
jmsp@freenet.co.uk
Post-herpetic neuralgia
Clinically, post-herpetic neuralgia (PHN) behaves as a References
‘‘central’’ or deafferentation pain, resistant to peripheral 1 Von Bokay J. Uber den atiologischen Zusammenhang der Varizellan mit
gewissen Fallen von Herpes Zoster Wien Zlin Wochenschr 1909;22:1323–6.
destructive procedures. [Bokay’s first paper Hungarian paper was published in 1892, translated by
Richard Bright suspected a link between herpes zoster and Jako& Jako, 1986, cited by Weller TH. In: Varicella-zoster virus, Ed Arvin AM,
the peripheral nerve apparatus in 1831.3 The first post- Gershon AA, Cambridge Univ Press, 2000 pp 9–25].
mortem examination—which identified the damage in the 2 Weller TH, Stoddard MB. Intranuclear inclusion bodies in cultures of human
dorsal root ganglion—was performed by von Bärensprung in tissue inoculated with varicella vesicle fluid. J Immunol 1952;68:311–9.
3 Bright R. Reports of Medical Cases, Selected With a View of Illustrating the
1861.4 Symptoms and Cure of Diseases by a Reference to Morbid Anatomy. 2
Medical knowledge remained rudimentary until Henry volumes, London, Longmans, 1827–1831. Facsimile of volume 1. London:
Head with A W Campbell (pathologist to Rainhill County Gower Publishers & Royal Society of Medicine, 1985, [The second part
Asylum) studied herpes zoster.5 6 Head lived in the hospital published in 1831 was devoted to the nervous system, illustrations appearing
in a separate volume].
for two years recording 450 cases and 21 autopsy studies.
4 Von Barensprung FGF. Betrage zur Kenntnis des Zoster. Berlin: Ann d Char
Foerster commended the accuracy of Head’s observations Krankenheit, 1862;10:96–104.
when compared to the method of section of nerve roots. 5 Head H, Campbell AW. The pathology of herpes zoster and its bearing on
Crucially, from this investigation the understanding of sensory localization. Brain 1900;23:353–529.
segmental dermatomes arose. Head and Campbell mapped 6 Henson RA. Henry Head: his influence on the development of ideas on
the dermatomes and showed that each corresponded to a sensation. Br Med Bull 1977;33:91–6.
single dorsal root ganglion (DRG). They characterised the 7 Zacks SI, Langfitt TW, Elliott FA. Herpetic neuritis: a light and electron
microscopic study. Neurology 1964;14:744–50.
onset and progression of the disease from ganglionitis to
8 Smith FP. Pathological studies of spinal nerve ganglia in relation to intractable
post-herpetic neuralgia. intercostal pain. Surgical Neurology 1978;10:50–3.
Despite these contributions the pathophysiology remained 9 Watson CPN, Deck JH. The neuropathology of herpes zoster with particular
incomplete. In 1964, Zacks, Langfitt, and Elliot7 reported on reference to postherpetic neuralgia and its pathogenesis. In: Watson CPN,
biopsied peripheral nerves in four zoster patients, two with eds. Herpes zoster and postherpetic neuralgia. Amsterdam: Elsevier,
1993:139–58.
post-herpetic neuralgia. Wallerian degeneration was present,
10 Watson CPN, Deck JH, Morshead C, et al. Postherpetic neuralgia: further
but neural fibrosis did not correlate with PHN. A central pain post-mortem studies of cases with and without pain. Pain 1991;44:105–17.
mechanism was suspected because few fibres remained. 11 Noordenbos W. Pain. Amsterdam: Elsevier, 1959:68–80.
Smith8 excised DRGs in 16 patients with intractable inter- 12 Melzack R, Wall PD. Pain mechanisms: a new theory. Science
costal PHN. Some were cystic and even at one year some were 1965;150:971–78.
infiltrated with chronic inflammatory cells. Watson and 13 Leading article. Postherpetic neuralgia. Lancet 1990;336:37–8.

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