NOCICEPTOR MODULATED CENTRAL SENSITIZATION CAUSES MECHANICAL HYPERALGESIA IN ACUTE CHEMOGENIC AND CHRONIC NEUROPATHIC PAIN

Brush-evoked pain (mechanical allodynia, dynamic mechanical hyperalges ia) is a hallmark of neuropathic and inflammatory pain states. Here we have examined the neural mechanisms that induce and maintain this com ponent of mechanical hyperalgesia. The principle finding of these expe riments is that the severity of brush-evoked pain correlates with the intensity of background pain in patients suffering from chronic painfu l neuropathies and in normal subjects with acute experimental chemogen ic pain. In experiments on nine normal subjects topical application of mustard oil for 5 min evoked strong burning pain and hyperalgesia to light mechanical stimuli. Differential nerve blocks (by compression of the superficial radial nerve) revealed that the brush-evoked pain was transmitted by A beta-fibres, which normally encode non-painful tacti le sensations, while the burning pain was signalled by C-fibres. Psych ophysical measurements showed that mustard oil treatment resulted in a pronounced sensitization of nociceptors to heat so that subsequent in nocuous changes of skin temperature from 35 to 40 degrees C resulted i n a proportional increase of burning background pain. Changes in the m agnitude of ongoing burning pain were closely correlated (r = 0.81) to the intensity of brush-evoked pain. While conduction block of A-fibre s eliminated only touch-evoked pain, blockade of C-fibre excitation in stantaneously abolished both ongoing and touch-evoked pain. In nine pa tients with chronic neuralgia (15 years mean duration) ongoing and bru sh-evoked pain were examined. In six patients, differential block of A beta-fibres eliminated touch-evoked pain, but ongoing pain persisted when only C-fibres were conducting. Complete relief of both ongoing an d stimulus-induced pain was obtained in two patients with intravenous regional guanethedine block and in two other individuals by local anae sthetic blocks of nerves supplying the symptomatic skin, indicating th at input from primaly afferents was necessary for the maintenance of t he pains and that ongoing pain was not self-perpetuated by central mec hanisms alone. Quantitative sensory tests revealed heat hyperalgesia i n four patients. fn those individuals, an increase of skin temperature produced a graded increase of their ongoing pain which was closely co rrelated (r = 0.94) with the level of brush-evoked pain. In the remain ing five patients there was no heat hyperalgesia and consequently no a ggravation of pain by increases of skin temperature. Nevertheless when the intensity of the background pain fluctuated spontaneously there w ere also parallel changes (r = 0.88) of the severity of brush-evoked p ain. We conclude that in normal volunteers, brush-evoked pain can be i nduced by short periods of nociceptive C-fibre excitation which induce s a state of central nervous sensitization as the basis of A beta-fibr e-mediated mechanical hyperalgesia. This central excitability increase , which permits brush-evoked pain to be expressed, is very malleable a nd depends critically on the continuous excitation of unmyelinated pri mary afferents. As a corollary, we propose that these mechanisms could account for ongoing and brush-evoked pain in chronic neuralgia, altho ugh they probably do not explain other sensory abnormalities observed in neuropathic pain states. This could mean that an excitation of prim ary nociceptive afferents is an important cause of neuropathic pain an d that the ensuing central mechanisms responsible for brush-evoked pai n are a normal sequel of nociceptor activation.