Slowly conducting afferents activated by innocuous low temperature in human skin

Campero, Mario; Serra, Jordi; Bostock, Hugh; Ochoa, José L.

doi:10.1111/j.1469-7793.2001.t01-1-00855.x

Cited by 172 publications

(142 citation statements)

References 31 publications

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“…Using a combination of calcium microfluorimetry and patch clamp, we have identified a novel type of cold-sensitive neuron with a transient response to a cooling step that was not activated or sensitized by the TRPM8 and TRPA1 agonists menthol or cinnamaldehyde (Babes et al 2006). The time course of this rapid adaptation to cold fits very well with the fast component of cold receptor adaptation measured in vivo (in the time range of seconds; Darian-Smith et al 1973;Kenshalo and Duclaux 1977;Campero et al 2001), which cannot be accounted for by TRPM8 or TRPA1, as both display much slower desensitization during cooling. Na v 1.8 is a voltage-gated, TTX-resistant sodium channel selectively expressed in small-diameter sensory neurons with nociceptive function (Akopian et al 1996).…”

Section: Other Thermo-sensitive Ion Channels That (May) Participate Isupporting

confidence: 52%

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Babeș

2009

Biophys Rev

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Substantial progress in understanding thermal transduction in peripheral sensory nerve endings was achieved with the recent cloning of six thermally gated ion channels from the TRP (transient receptor potential) super-family. Two of these channels, TRP melastatin 8 (TRPM8) and TRP ankyrin 1 (TRPA1), are expressed in dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons, are activated by various degrees of cooling, and are candidates for mediating gentle cooling and noxious cold, respectively. However, accumulating evidence suggests that more than just these two channels are involved in cold sensing in mammals. A recent report described a critical role of the voltage-gated tetrodotoxin-resistant sodium channel Na v 1.8 in perceiving intense cold and noxious stimuli at cold temperatures. Other ion channels, such as two-pore domain background potassium channels (K2P), are known to be expressed in peripheral nerves, have pronounced temperature dependence, and may contribute to cold sensing and/or cold hypersensitivity in pain states. This article reviews the evidence supporting a role for each of these channels in cold transduction, focusing on their biophysical properties, expression pattern, and modulation by pro-inflammatory mediators.

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Section: Other Thermo-sensitive Ion Channels That (May) Participate Isupporting

confidence: 52%

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Babeș

2009

Biophys Rev

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“…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. More recently, Campero et al (2001) discovered cold-sensitive C-fibers in humans that discharge statically to temperatures up to 30°C yet respond maximally below 20°C. These C-fibers and the sensitive C-mechanothermal nociceptors described by Georgopoulos (1976) could potentially mediate cold LTN ≤30°C, although Campero et al (2001) questioned whether the C-fibers contribute to thermal perception after a vigorous discharge in one of the fibers failed to evoke a sensation.…”

Section: Discussionmentioning

confidence: 99%

“…However, the possibility that LTN arises from classically defined cold fibers and warm fibers cannot be ruled out, as the thresholds of fibers that express TRPM8 and TRPV3 fall within the range of putative cold and warm fibers. Support for involvement of cold fibers comes from their 'paradoxical' response to high temperatures (Dodt and Zotterman 1952;Long 1973;Campero et al 2001) and from the phenomenon of the heat grill illusion, or 'synthetic heat' (Green 1977;Green 2002;Fruhstorfer et al 2003). Whereas the high threshold [>50°C; (Long 1977)] and temporal irregularity of the paradoxical discharge rule out a role for cold fibers in encoding heat pain, evidence that repeated heating sensitizes cold fibers to heat and lowered the threshold of the paradoxical discharge (Dubner et al 1975;Long 1977) led to speculation that cold fibers may contribute to heat hyperalgesia (Dubner et al 1975;Price and Dubner 1977).…”

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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“…While these studies have provided the basis for well-established notions, such as fibers specificity in humans (i.e. the class of specific nerve fibers which are involved in warm and cold temperatures detection), recent evidence based on microneurographic recordings of activity in primary thermo-sensory nerve fibers in awake humans has challenged some of these well-established ideas (39,40,264).…”

Section: Neurophysiology Of Temperature Sensationmentioning

confidence: 99%

Neurophysiology of Skin Thermal Sensations

Filingeri

2016

Comprehensive Physiology

104

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Undoubtedly, adjusting our thermoregulatory behavior represents the most effective mechanism to maintain thermal homeostasis and ensure survival in the diverse thermal environments that we face on this planet. Remarkably, our thermal behavior is entirely dependent on the ability to detect variations in our internal (i.e. body) and external environment, via sensing changes in skin temperature and wetness. In the past 30 years, we have seen a significant expansion of our understanding of the molecular, neuroanatomical and neurophysiological mechanisms that allow humans to sense temperature and humidity. The discovery of temperature-activated ion channels which gate the generation of action potentials in thermosensitive neurons, along with the characterization of the spino-thalamo-cortical thermosensory pathway, and the development of neural models for the perception of skin wetness, are only some of the recent advances which have provided incredible insights on how biophysical changes in skin temperature and wetness are transduced into those neural signals which constitute the physiological substrate of skin thermal and wetness sensations. Understanding how afferent thermal inputs are integrated and how these contribute to behavioral and autonomic thermoregulatory responses under normal brain function is critical to determine how these mechanisms are disrupted in those neurological conditions which see the concurrent presence of afferent thermosensory abnormalities and efferent thermoregulatory dysfunctions. Furthermore, advancing the knowledge on skin thermal and wetness sensations is crucial to support the development of neuro-prosthetics. In light of the above, this review will focus on the peripheral and central neurophysiological mechanisms underpinning skin thermal and wetness sensations in humans.

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Slowly conducting afferents activated by innocuous low temperature in human skin

Cited by 172 publications

References 31 publications

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

Ion channels involved in cold detection in mammals: TRP and non-TRP mechanisms

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

Neurophysiology of Skin Thermal Sensations

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