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The Journal of Neuroscience, June 1, 2003, 23(11):4766-4774

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Fatigue and Paradoxical Enhancement of Heat Response in C-Fiber Nociceptors from Cross-Modal Excitation

Yuan B. Peng,¹ Matthias Ringkamp,¹ Richard A. Meyer,^1,2 and James N. Campbell^1,2

¹ Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, and ² Johns Hopkins Applied Physics Laboratory, Laurel, Maryland 20723

Fatigue refers to the decrement of response seen with repeated stimulation and is a prominent attribute of nociceptors. Whether fatigue in nociceptors involves transduction, spike initiation, or conduction mechanisms is unknown. We investigated systematically how electrical, mechanical, and heat conditioning stimuli (eCS, mCS, hCS) affected the subsequent response to a test-heat stimulus applied 5 sec later to the receptive field of cutaneous nociceptors. Standard teased-fiber techniques were used to record from mechano–heat-sensitive C-fiber afferents in the anesthetized monkey. The eCS was applied to the nerve trunk, whereas the hCS and mCS were applied to the heat-test site. For the eCS, the number of pulses rather than frequency of stimulation determined the level of fatigue. Fatigue varied inversely with the time interval between the eCS and the test stimulus. For comparable responses from the CS, the magnitude of fatigue was less after the mCS than after the eCS. The mCS (but not the eCS) sometimes evoked a paradoxical increase in response to the test-heat stimulus. Recovery from fatigue was significantly faster after the eCS and mCS than the hCS. The paradoxical enhancement after the mCS probably results from temporal summation of generator potentials produced by mechanical and heat stimulation and suggests that the time constant of the generator potential is on the order of seconds. Concurrent enhancement–fatigue effects may also explain why fatigue was less after the mCS than the eCS. The dependency of recovery from fatigue on the modality of the CS suggests that fatigue results from transduction–spike initiation mechanisms.

Key words: pain; somatosensory system; primary afferents; adaptation; fatigue; sensitization; nociceptors

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Received Sep. 10, 2002; revised Jan. 16, 2003; accepted Mar. 14, 2003.

This article has been cited by other articles:

				W. Greffrath, S. T. Schwarz, D. Busselberg, and R.-D. Treede Heat-Induced Action Potential Discharges in Nociceptive Primary Sensory Neurons of Rats J Neurophysiol, July 1, 2009; 102(1): 424 - 436. [Abstract] [Full Text] [PDF]

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