Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli.

Bessou, P; Perl, Edward R.

doi:10.1152/jn.1969.32.6.1025

Cited by 934 publications

(398 citation statements)

References 18 publications

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“…As presented here and elsewhere (Thut et al 2003), HT cool neurons also differ from LT cool neurons in the threshold and kinetics of their responses to cooling, cell body size, and IB4 binding. The notion that there are distinct populations of sensory neurons responsive to a decrease in temperature is consistent with electrophysiological and psychophysical studies, suggesting that at least two unique populations of cold-sensitive neurons exist in vivo: one population that is responsive to innocuous cooling and a second responsive to noxious cold (Bessou and Perl 1969;Darian-Smith et al 1973;Georgopoulos 1976;Iggo 1969). LT cool neurons and HT cool neurons may therefore represent cool fibers and cold nociceptors, respectively.…”

Section: Discussionsupporting

confidence: 56%

TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

Nealen¹,

Gold

Thut

et al. 2003

Journal of Neurophysiology

150

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. TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol 90: 515-520, 2003. First published March 12, 2003 10.1152/jn.00843.2002. Recent electrophysiological studies of cultured dorsal root and trigeminal ganglion neurons have suggested that multiple ionic mechanisms underlie the peripheral detection of cold temperatures. Several candidate "cold receptors," all of them ion channel proteins, have been implicated in this process. One of the most promising candidates is TRPM8, a nonselective cationic channel expressed in a subpopulation of sensory neurons that is activated both by decreases in temperature and the cooling compound menthol. However, evidence for the expression of TRPM8 in functionally defined cold-sensitive neurons has been lacking. Here, we combine fluorometric calcium imaging of cultured rat trigeminal neurons with single-cell RT-PCR to demonstrate that there are distinct subpopulations of cold responsive neurons and that TRPM8 likely contributes to cold transduction in one of them. TRPM8 is preferentially expressed within a subset of rapidly responsive, low-threshold (approximately 30°C), cold-sensitive neurons. A distinct class of slowly responsive cold-sensitive neurons that is activated at lower temperatures (approximately 20°C) generally lacks detectable TRPM8 mRNA. Together with previous findings, our data support the notion that cold responsive neurons are functionally heterogeneous.

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Section: Discussionsupporting

confidence: 56%

TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

Nealen¹,

Gold

Thut

et al. 2003

Journal of Neurophysiology

150

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“…The increase in peak discharge rate with stimulus ramp rate indicates a higher sensitivity to fast temperature changes and has usually been related to the phasic response characteristics of nociceptors. In summary, heat conduction to the receptor and the phasic response characteristics of nociceptors explain the apparent paradox described by Bessou & Perl (1969). Correlations between psychophysical measures of heat pain threshold and neurophysiological results Unlike CMH thresholds, human pain thresholds decrease as stimulus ramp rate increases.…”

Section: Resultsmentioning

confidence: 83%

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans.

Tillman¹,

Treede²,

Meyer³

et al. 1995

The Journal of Physiology

106

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1. Ramped heat stimuli were used to compare the effects of rate of temperature change on the responses of monkey nociceptors and on heat pain threshold in human subjects. Recordings were made from twenty-five cutaneous C fibre mechano-heat nociceptors (CMHs) innervating the hairy skin in the anaesthetized monkey. Heat pain thresholds were determined on the volar forearm of eight human subjects using a converging staircase technique. 2. The heat pain threshold decreased as stimulus ramp rate increased. In contrast, the CMH heat threshold, defined as the surface temperature at which the first action potential occurred, increased as stimulus ramp rate increased. Thus, the properties of the heat stimulus that dictate heat pain threshold are different from the properties of the heat stimulus that govern the initiation of a response in nociceptors. 3. Peak discharge frequency of CMHs during the heat ramp increased with stimulus ramp rate.Heat pain threshold was correlated with achievement of a minimum discharge rate in nociceptors (0 5 Hz), rather than with the threshold for action potential initiation.

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“…Although the spots were detected at temperatures served by cold fibers and warm fibers, it has been assumed that sensations of burning, stinging or pricking arise from stimulation of nociceptors, which by definition have high thresholds and respond to noxious stimulation (Bessou and Perl 1969;Iggo and Ogawa 1971). The test temperatures of 28° and 36°C were specifically chosen to avoid stimulation of C-polymodal nociceptors (CPNs), which have average cold thresholds below 20°C (Simone and Kajander 1996;Campero et al 1996) and average heat thresholds above 40°C (Bessou and Perl 1969;Van Hees and Gybels 1981;Yarnitsky et al 1992). However, Georgopoulos (1976) reported a few Aδ-and C-mechano-thermal nociceptors in primates that were unusually sensitive to cold, with some having thresholds as high as 30°C.…”

Section: Discussionmentioning

confidence: 99%

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

Green

Roman

Schoen

et al. 2008

Pain

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It was recently found that nociceptive sensations (stinging, pricking, or burning) can be evoked by cooling or heating the skin to innocuous temperatures (e.g., 29°, 37°C). Here we show that this lowthreshold thermal nociception (LTN) can be traced to sensitive 'spots' in the skin equivalent to classically defined warm spots and cold spots. Because earlier work had shown that LTN is inhibited by simply touching a thermode to the skin, a spatial search procedure was devised that minimized tactile stimulation by sliding small thermodes (16 mm 2 and 1 mm 2 ) set to 28° or 36°C slowly across the lubricated skin of the forearm. The procedure uncovered three types of temperature-sensitive sites (thermal, bimodal and nociceptive) that contained one or more thermal, nociceptive or (rarely) bimodal spots. Repeated testing indicated that bimodal and nociceptive sites were less stable over time than thermal sites, and that mechanical contact differentially inhibited nociceptive sensations. Intensity ratings collected over a range of temperatures showed that LTN increased monotonically on heat-sensitive sites but not on cold-sensitive sites. These results provide psychophysical evidence that stimulation from primary afferent fibers with thresholds in the range of warm fibers and cold fibers is relayed to the pain pathway. However, the labile nature of LTN implies that these lowthreshold nociceptive inputs are subject to inhibitory controls. The implications of these findings for the roles of putative temperature receptors and nociceptors in innocuous thermoreception and thermal pain are discussed.

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Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli.

Cited by 934 publications

References 18 publications

TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans.

Nociceptive sensations evoked from ‘spots’ in the skin by mild cooling and heating

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