Brain, Vol. 117, No. 3, 579-591, 1994
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Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain
1Department of Neurology, University of Würzburg Germany 2Department of Clinical Neurophysiology, University Hospital Uppsala, Sweden
Correspondence to:
Correspondence to: Martin Koltzenburg, Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany
Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalgesia) is a hallmark of neuropathic and inflammatory pain states. Here we have examined the neural mechanisms that induce and maintain this component of mechanical hyperalgesis. The principle finding of these experiments is that the severity of brush-evoked pain correlates with the intensity of backgound pain in patients suffering from chronic painful neuropathies and in normal subjkects with acute experimental chemogenic pain.
In experiments on nine normal subjects topical application of mustrard oil for 5 min evoked strong buring pain and hyperalgesia to light mechanical stimuli. Differential nerve blocks (by comparession of the superficial radial nerve) revealed that the brush-evoked pain was transmitted by Aß-fibers, which normally encode non-painful tactile sensations, while the buring pain was signalled by C-fibers. Psychophysical measurements showed that mustard oil treatment resulted in a pronounced sensitization of nociceptors to heat so that subsequent innocuous changes of skin temperature from 35 to 40°C resulted in a proprotional rincrease of buring background pain. Changes in the magnitucde of ongoing buring pain were closely correlated (r = 0.81) to the intensity of brush-evoked pain. While conduction block of A-fibers eliminated only touch-evoked pain, blocked of C-fibre exciation instantaneously abolished both ongoing and touch-evoked pain.
In nine patients with chronic neuralgia (15 years mean duration) ongoing and brush-evoked pain were examined. In six patients, differential block of Aß-fibres eliminated touch-evoked pain, but ongoing pain persisted when only C-fibres were conducting. Complete relief of both ongiong and stimulus-induced pain was obtained in two patients with intravenous regional guanethedine block and in two other individuals by local anaesthetic blocks of nerves supplying the symptomatic skin, indicating that input from primary afferents was necessary for the maintenance of the pains and that ongoing pain was not self-perpetuated by central mechanisms alone. Quantitative sensory tests revealed heat hyperalgesia in four patients. In those individuals, an increase of skin temperature produced a granded increase of their ongoing pain which was closely correlated (r= 0.94) with the level of brush-evoked pain. In the remaining five patients there was no heat hyperalgesia and consequently no aggravation of pain increases of skin temperature. Nevertheless when the intensity of the background pain fluctuated spontaneously there were also parallel changes (r = 0.08) of the severity of brush-evoked pain.
We conclude that in normal volunteers, brush-evoked pain can be induced by short periods of nociceptive C-fibre excitation which induces a state of central nervous sensitization as the basis of Aß-fibre-mediated mechanical hyperalgesia. This central excitability increase, which permits brush-evoked pain to be expressed, is very malleable and depends critically on the continuous excitation of unm7yelinated primary afferents. As a corollary, we propose that these mechanisms could account for ongoing and brush-evoked pain in chronic neuralgia, although they probably do not explain other sensory abnormalities observed in neuropathic pain states. This could mean than an excitation of primary nociceptive afferents is an important cause of neuropathic pain and that the ensuing central mechanisms responsible for brush-evoked pain are a normal sequel of nociceptro activation.
allodynia; neuralgia; nociceptor sensitization; central sebsutuzation; sympathetically maintained pain
Received October 22, 1993. Accepted January 11, 1994.
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