Noxious heat receptors present in cold-sensory cells in rats

Okazawa, Makoto; Inoue, Wataru; Hori, Aiko; Hosokawa, Hiroshi; Matsumura, Kiyoshi; Kobayashi, Shígeo

doi:10.1016/j.neulet.2004.01.074

Cited by 81 publications

(56 citation statements)

References 15 publications

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“…Recently, we found that a subpopulation of neurons with nociceptive properties (e.g., capsaicin sensitivity) also expresses functional TRPM8 receptors, but their expression level is low (Xing et al, 2006). Consistently, two other recent studies showed detectable TRPM8-IR in some TRPV1-expressing neurons of rats (Okazawa et al, 2004;Abe et al, 2005).…”

Section: Introductionsupporting

confidence: 79%

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Xiao¹,

Chen²,

Ling³

et al. 2007

J. Neurosci.

206

177

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The cold-and menthol-sensitive receptor TRPM8 (transient receptor potential melastatin 8) has been suggested to play a role in cold allodynia, an intractable pain seen clinically. We studied how TRPM8 is involved in cold allodynia using rats with chronic constrictive nerve injury (CCI), a neuropathic pain model manifesting cold allodynia in hindlimbs. We found that cold allodynic response in the CCI animals was significantly attenuated by capsazepine, a blocker for both TRPM8 and TRPV1 (transient receptor potential vanilloid 1) receptors, but not by the selective TRPV1 antagonist I-RTX (5-iodoresiniferatoxin). In L5 dorsal root ganglion (DRG) sections of the CCI rats, immunostaining showed an increase in the percentage of TRPM8-immunoreactive neurons when compared with the sham group. Using the Ca 2ϩ -imaging technique and neurons acutely dissociated from the L5 DRGs, we found that CCI resulted in a significant increase in the percentage of menthol-and cold-sensitive neurons and also a substantial enhancement in the responsiveness of these neurons to both menthol and innocuous cold. These changes occurred in capsaicin-sensitive neurons, a subpopulation of nociceptive-like neurons. Using patch-clamp recordings, we found that membrane currents evoked by both menthol and innocuous cold were significantly enhanced in the CCI group compared with the sham group. By retrograde labeling afferent neurons that target hindlimb skin, we showed that the skin neurons expressed TRPM8 receptors, that the percentage of menthol-sensitive/cold-sensitive/capsaicin-sensitive neurons increased, and that the menthol-and cold-evoked responses were significantly enhanced in capsaicin-sensitive neurons after CCI. Together, the gain of TRPM8-mediated cold sensitivity on nociceptive afferent neurons provides a mechanism of cold allodynia.

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Section: Introductionsupporting

confidence: 79%

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

Xiao¹,

Chen²,

Ling³

et al. 2007

J. Neurosci.

206

177

View full text Add to dashboard Cite

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“…In addition, TRPV3 continues to respond to painfully hot temperatures (Peier et al 2002b) knockout mice that lack TRPV3 show deficits in response to both noxious and innocuous heat (Moqrich et al 2005). Similarly, the menthol and cold receptor TRPM8 (McKemy et al 2002;Peier et al 2002a), which was recently shown in mice to be the principal receptor for cold below 30°C (Bautista et al 2007;Colburn et al 2007;Dhaka et al 2007;see however Munns et al 2007), has been reported in some DRG and trigeminal ganglion neurons that are capsaicin-sensitive and/or were shown to express TRPV1 (McKemy et al 2002;Okazawa et al 2004;Abe et al 2005;Xing et al 2006;Hjerling-Leffler et al 2007). (See, however, Kobayashi et al 2005.…”

Section: Discussionmentioning

confidence: 96%

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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“…At a concentration of 100 μM antagonist, 4 of 6 fish showed surgical anesthetic response to menthol, but others did not showed surgical anesthesia within 6 min. Pretreatment of the antagonist with 100 μM significantly (P < 0.01) prolonged (20)(20)(20) (20)(20)(20) (20)(20)(20) (12)(12)(12) (12)(12) (12)(12)(12) (12) (12) (12) A 1.0 [12][12] [12] (12) (12)(12) 1.0 1.0 [12][12] [12] 1.0 [12] the latency to 351 ± 5 s (n = 4) in (Fig. 4A).…”

Section: Effects Of Gaba and Gaba A -Antagonist On Mentholinduced Anementioning

confidence: 99%

“…The cold-and menthol-sensitive receptor 1 (CMR1) or transient receptor potential melastatin-8 (TRPM8) has been recognized as a member of transient receptor potential (TRP) family of excitatory ion channels and functions as a transducer of cold stimuli in the somatosensory systems [9,10]. TRPM8 receptors are widely expressed and are considered to function specifically as cold receptors in tyrosine kinase receptor A (TrkA + ) affected smalldiameter primary sensory neurons [9,[11][12][13][14]. At relatively high concentrations, topical application of menthol induces cold pain and hyperalgesia, possibly via activation of both cold-sensitive C-type nociceptors and A -fibers [5,15].…”

Section: Introductionmentioning

confidence: 99%

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

Kasai¹,

Hososhima²,

Yun-Fei³

2014

TONEURJ

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Abstract:To determine whether fishes respond to menthol, Japanese medaka Oryzias latipes, goldfish Carassius auratus, and zebrafish Danio rerio were exposed to various types of menthol receptors agonists and the behavioral responses to these drugs were observed. Waterbone application of dl-menthol (0.5 mM) induced surgical anesthesia in 100% of medaka, 90% of goldfish, and 100% of zebrafish. The percentage of response increased dose-dependently from 0.2 mM to 0.5 mM. There were no differences in either percentage or latency of the response in surgical anesthesia among dl-, d-, and l-types of menthol. A high (3.0 mM) concentration of any of the three types of menthol induced rapid movement followed by the anesthetic response. Rapid movement was observed with allyl isothiocyanate, a cold nociceptor agonist, but not with icilin, a cold receptor agonist, in medaka and goldfish. Both allyl isothiocyanate and icilin failed to induce surgical anesthesia. To determine the involvement of -aminobutyric acid (GABA) system in menthol-induced surgical anesthesia, the effect of the receptors antagonist for the GABA A was tested. Pretreatment with a specific GABA A receptor antagonist prolonged the latency of the anesthetic response to menthol, but not to cold-water stimulation, in medaka and goldfish. These results demonstrate that menthol can play a role in the induction of surgical anesthesia in fishes, related at least in part to the activation of GABA A receptors, and of rapid movement possibly via cold nociceptors.

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Noxious heat receptors present in cold-sensory cells in rats

Cited by 81 publications

References 15 publications

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

TRPM8 Mechanism of Cold Allodynia after Chronic Nerve Injury

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

Menthol Induces Surgical Anesthesia and Rapid Movement in Fishes

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