Neurogenic hyperalgesia: Central neural correlates in responses of spinothalamic tract neurons

D. A. Simone, L. S. Sorkin, U. Oh, J. M. Chung, C. Owens, R. H. LaMotte, W. D. Willis

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The contribution of activity in spinothalamic tract (STT) neurons to the pain and neurogenic hyperalgesia produced by an intradermal injection of 100 μg of capsaicin was investigated. Electrophysiological responses of identified STT neurons recorded in anesthetized monkeys were compared with psychophysical measurements of pain and hyperalgesia obtained in humans using identical stimuli. Magnitude estimates of pain in humans were obtained after an injection of capsaicin or the vehicle. Capsaicin produced immediate burning pain that was most intense within 15 s after injection and then declined over the next 10-30 min. The vehicle produced no pain. Cutaneous hyperalgesia to gentle stroking (allodynia) and also hyperalgesia to punctate stimulation developed in a wide area surrounding the capsaicin injection. Within this area, magnitude estimates of pain produced by a punctate stimulus (von Frey type with force of 225 mN) increased over preinjection values by an average of sixfold at test sites 1, 2, and 3 cm away from the injection site. At the capsaicin injection site, magnitude estimates of pain in response to punctate simulation typically remained the same or were decreased. After capsaicin, but not vehicle, the mean heat pain thresholds were lowered from ~45°C before injection to 34°C after, but only in the immediate vicinity of the injection site. At a site located 2 cm away, the thresholds were not significantly altered. Similarly, magnitude estimates of pain produced by suprathreshold heat stimuli were increased after capsaicin only at the injection site. STT neurons were classified as high-threshold (HT) or wide-dynamic-range (WDR) cells according to responses evoked by graded cutaneous mechanical stimulation. An intradermal injection of capsaicin excited 4 of 7 HT cells and 10 of 12 WDR cells. The discharge rates of STT neurons correlated in time course with the magnitude estimates of pain in humans. The correlation was considerably better for WDR than for HT neurons, suggesting a predominant contribution of WDR neurons to the pain from capsaicin. Capsaicin significantly increased the responses of HT neurons (9-fold) and the responses of WDR neurons (2-fold) to stroking the skin within the receptive field. Similar increases in responses to a standard punctate stimulus were observed at test sites, 1, 2, and 3 cm away from the injection site. After injection of vehicle, the responses to punctate stimulation increased by a mean of only 1.2- and 1.4-fold for HT and WDR neurons, respectively. Thus the increased responsiveness of both HT and WDR STT neurons is likely to contribute to the mechanical hyperalgesia produced by capsaicin. The mean heat thresholds for 12 WDR neurons decreased at the capsaicin injection site from 48.3 ± 0.8°C before the injection of capsaicin to 32.3 ± 1°C after. The responses to suprathreshold heat stimuli were also enhanced. With the exception of one neuron, the responses to heat applied 2 cm away from the capsaicin injection site were unchanged. Heat thresholds were not changed significantly on or away from the vehicle injection site before and after injection of vehicle. Only one of the HT neurons responded consistently to heat and the responses were not appreciably altered after either vehicle or capsaicin. We conclude that the heat sensitization of WDR neurons contributes to the heat hyperalgesia after a capsaicin injection. In six of eight cells tested (1 HT and 5 WDR), responses evoked by electrical stimulation of the proximal end of a cut dorsal rootlet-at intensities sufficient to activate only large myelinated afferent fibers-increased significantly after capsaicin but not after vehicle. This suggests that intradermal injection of capsaicin increases the excitability of dorsal horn neurons. It is concluded that activity in STT neurons contributes to the pain and hyperalgesia produced by a cutaneous injury, in this case a chemical injury. Enhanced responses of STT neurons evoked by cutaneous stimulation after capsaicin are mediated, at least in part, by an increase in central excitability. These results support the hypothesis that certain neurons within the dorsal horn of the spinal cord become sensitized during neurogenic hyperalgesia.

Original languageEnglish (US)
Pages (from-to)228-246
Number of pages19
JournalJournal of neurophysiology
Issue number1
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology


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