OSM-9 and OCR-2 TRPV channels are accessorial warm receptors in Caenorhabditis elegans temperature acclimatisation

Caenorhabditis elegans (C. elegans) exhibits cold tolerance and temperature acclimatisation regulated by a small number of head sensory neurons, such as the ADL temperature-sensing neurons that express three transient receptor potential vanilloid (TRPV) channel subunits, OSM-9, OCR-2, and OCR-1. Here, we show that an OSM-9/OCR-2 regulates temperature acclimatisation and acts as an accessorial warmth-sensing receptor in ADL neurons. Caenorhabditis elegans TRPV channel mutants showed abnormal temperature acclimatisation. Ectopic expression of OSM-9 and OCR-2 in non-warming-responsive gustatory neurons in C. elegans and Xenopus oocytes revealed that OSM-9 and OCR-2 cooperatively responded to warming; however, neither TRPV subunit alone was responsive to warming. A warming-induced OSM-9/OCR-2-mediated current was detectable in Xenopus oocytes, yet ADL in osm-9 ocr-2 double mutant responds to warming; therefore, an OSM-9/OCR-2 TRPV channel and as yet unidentified temperature receptor might coordinate transmission of temperature signalling in ADL temperature-sensing neurons. This study demonstrates direct sensation of warming by TRPV channels in C. elegans.

The Mechanism of Moxibustion: Ancient Theory and Modern Research

The moxibustion has a dual effect of tonification and purgation in TCM theories, which are based on two aspects: the actions of the meridian system and the roles of moxa and fire. Modern research works of the moxibustion mechanism mainly relate to the thermal effects, radiation effects, and pharmacological actions of moxa and its combustion products. Experimental results showed that moxibustion thermal stimulation affects both shallow and deep tissues of the skin, and the warm-heat effects of moxibustion have a close relation to the warm receptors or/and the polymodal receptor. The burning moxa radiation spectrum ranges from 0.8 to 5.6 μm; peak is nearby 1.5 μm, lying within the near infrared portion. There is an amazing consistency in the infrared spectrums of three types of indirect moxibustion and the unified spectrum of acupoints; all have their peaks of radiation near 10 μm. Lots of ingredients had been identified from mugwort leaves and moxa smoke, which have a variety of biological activities; they were considered to participate in the comprehensive effects of moxibustion. Although lots of research works have been carried out and made some progress, there is still a great distance from fully understanding the mechanism of moxibustion.

Facilitation of a Nociceptive Flexion Reflex in Man by Nonnoxious Radiant Heat Produced by a Laser

Plaghki, Léon, Dominique Bragard, Daniel Le Bars, Jean-Claude Willer, and Jean-Marie Godfraind. Facilitation of a nociceptive flexion reflex in man by nonnoxious radiant heat produced by a laser. J. Neurophysiol. 79: 2557–2567, 1998. Electromyographic recordings were made in healthy volunteers from the knee-flexor biceps femoris muscle of the nociceptive RIII reflex elicited by electrical stimulation of the cutaneous sural nerve. The stimulus intensity was adjusted to produce a moderate pricking-pain sensation. The test responses were conditioned by a nonnoxious thermal (≤40°C) stimulus applied to the receptive field of the sural nerve. This stimulus was delivered by a CO2 laser stimulator and consisted of a 100-ms pulse of heat with a beam diameter of 20 mm. Its power was 22.7 ± 4.2 W (7.2 mJ/mm2), and it produced a sensation of warmth. The maximum surface temperature reached at the end of the period of stimulation was calculated to be 7°C above the actual reference temperature of the skin (32°C). The interval between the laser (conditioning) and electrical (test) stimuli was varied from 50 to 3,000 ms in steps of 50 ms. It was found that the nociceptive flexion reflex was facilitated by the thermal stimulus; this modulation occurred with particular conditioning-test intervals, which peaked at 500 and 1,100 ms with an additional late, long-lasting phase between 1,600 and 2,300 ms. It was calculated that the conduction velocities of the cutaneous afferent fibers responsible for facilitating the RIII reflex, fell into three ranges: one corresponding to Aδ fibers (3.2 m/s) and two in the C fiber range (1.3 and 0.7 m/s). It is concluded that information emanating from warm receptors and nociceptors converges. In this respect, the present data show, for the first time, that in man, conditioning nonnociceptive warm thermoreceptive Aδ and C fibers results in an interaction at the spinal level with a nociceptive reflex. This interaction may constitute a useful means whereby signals add together to trigger flexion reflexes in defensive reactions and other basic motor behaviors. It also may contribute to hyperalgesia in inflammatory processes. The methodology used in this study appears to be a useful noninvasive tool for exploring the thermoalgesic mechanisms in both experimental and clinical situations.

Threshold for detecting temperature changes in a spider thermoreceptor

1. The threshold for detecting a change in temperature of a warm receptor in the wandering spider Cupiennius salei was determined by means of its frequency-dependent noise. To accomplish this, the warm receptor was regarded as a linear system consisting of two components, an amplifier (gain of the frequency response) and noise at its input added to the temperature stimulus (input noise density). 2. The frequency response was investigated with sinusoidal temperature modulations at frequencies between 0.05 and 12.8 Hz. The gain increased by 3.5 dB/octave in the frequency range between 0.05 and 6.4 Hz, from 0.19 to 3.1 degrees C-1. However, at the highest frequency, 12.8 Hz, the gain was reduced. 3. The noise density of the warm receptor was measured by the root-mean-square noise amplitude of the gain. The output noise density of the warm receptor, which describes the noise density of the gain, was constant at approximately 0.2 Hz-0.5 in the 0.05 to 6.4 Hz range, and increased at higher frequencies. The input noise density, given by the ratio of output noise density to gain, decreased by -2.7 dB/octave between 0.05 and 6.4 Hz, from 1.1 to 0.12 degrees C*Hz-0.5. 4. To define the threshold for detection of temperature changes from the input noise density, the energy of the threshold was equated to the energy of the noise. Assuming a signal-to-noise ratio of 1 and an upper limiting frequency of 10 Hz, the threshold estimated for the wandering spider Cupiennius ranges from 0.6 to 0.08 degrees C, depending on whether the inputs from only 1 or all 70 warm receptors of the 10 tarsal organs are combined.

Fos-like immunoreactivity in the superficial medullary dorsal horn induced by noxious and innocuous thermal stimulation of facial skin in the rat

1. To examine further the ability of different classes of nociceptive and nonnociceptive primary afferent neurons to induce c-fos expression in central neurons, fos-like immunoreactivity was examined in the medullary dorsal horn (laminae I-IV) of the rat after facial application of a range of warming and cooling thermal stimuli. Urethan-anesthetized rats received 15 30-s thermal pulses (53, 50, 47, 41, 25, or 10 degrees C) applied to the vibrissal pad over a period of 30 min and were perfused 2 h after the end of stimulation. 2. Stimulation of 41 degrees C produced no significant increase in the number of fos-LI-labeled cells in lamina I or II compared with control (35 degrees C) animals. 3. Stimulation of 47 degrees C produced a significant increase in the number of fos-LI-labeled cells in both laminae I and II. Stimulation of 50 degrees C produced a significant increase in labeling, compared with that produced by 47 degrees C, which was primarily in lamina II. Stimulation of 53 degrees C produced no further increase in the number of labeled cells, compared with that produced by 50 degrees C, in lamina I or II. 4. In the cooling direction, 25 degrees C produced a significant increase in labeling above control levels in both lamina I and II, whereas 10 degrees C produced a further increase compared with 25 degrees C, which was restricted to lamina I. 5. None of the stimuli produced a significant increase in labeling in laminae III-IV. 6. The results are interpreted as providing evidence that low-threshold cold receptors, high-threshold cold receptors, and nociceptors are capable of inducing fos expression in dorsal horn neurons, whereas warm receptors are relatively ineffective. The results also provide evidence that neurons that receive input from C polymodal nociceptors are present in both laminae I and II, as are neurons that receive input from low-threshold cold receptors. Neurons that receive input from high-threshold cold receptors, but not from low-threshold cold receptors, appear to be located preferentially in lamina I. The shape of the curve relating fos-LI labeling to stimulus temperature in the warming direction is consistent with the expected pattern of recruitment of primary afferent nociceptors.

Cutaneous sensory receptors in the rat foot

1. A total of 574 cutaneous afferent units in the sural and plantar nerves supplying the skin of the rat foot was examined: 399 A beta-units, 55 A delta-units, and 120 C-units. Their receptive-field (RF) properties were similar to those described in other mammals. However, the receptor type composition of units was different between the two nerves. 2. The sural A beta-fiber sample (n = 160) consisted of G-hair (41%), field (11%), rapidly adapting (RA; 6%), slowly adapting type I (SA-I; 7%), and type II (SA-II; 35%) mechanoreceptors. The plantar A beta-fiber sample (n = 239) was composed of G-hair (3%), RA (35%), SA-I (30%), SA-II (24%), and Pacinian corpuscle (PC; 8%) mechanoreceptors. 3. The RFs of SA-II units were located on both hairy and glabrous skin overlying the foot joints. Many of the SA-II units responded to movement of the foot joints. The RFs of both SA-I and RA units were small in size and located in high density on the toe tips and footpads. PC units were very sensitive to vibration and had extremely large RFs as in other species, although they were rare and found only in the plantar nerve. Field units were similar to SA-II units in response properties and RF distribution. 4. The sural A delta-fiber sample (n = 44) included nociceptors (68%), D-hair (27%), and cold (5%) receptors. All sampled plantar A delta-fibers (n = 11) were nociceptors. Of A delta-nociceptor units, A delta-mechanical nociceptors (73%) were dominant. 5. The sural C-fiber sample (n = 85) included nociceptors (44%), C-mechanoreceptors (33%), and cold receptors (21%). The plantar C-fiber sample (n = 35) included nociceptors (77%) and cold receptors (23%). No warm units were found among either the sural or plantar nerve fibers. Of C-nociceptors, C-mechanoheat nociceptors (80%) were dominant. 6. The results indicate that all well-known types of cutaneous receptors, except warm receptors, exist in the foot skin of the rat. On the basis of the fact that RFs of RA and SA-I units are in high density on the toe tips and footpads, it is suggested that those regions may have a spatial discriminating capacity. It is also suggested that SA-II receptors may play a role in proprioception, because they have RFs on the skin over foot joints and respond to joint movement.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of cold and capsaicin desensitization on prostaglandin E hypothermia in rats

Intraperitoneal injection of prostaglandin E1 (PGE) produces a transient hypothermia in rats that lasts 1-2 h. Rats exposed to an ambient temperature (Ta) of 26 degrees C displayed a decrease in rectal temperature (Tre) of 0.95 +/- 0.12 degrees C (SE) after injection with PGE (100 micrograms/kg ip). Hypothermia was produced mainly by heat losses, as indicated by increases in tail blood flow. At Ta of 4 degrees C, PGE produced a comparable fall in Tre of 1.00 +/- 0.14 degrees C. However, in the cold the hypothermia was caused solely by decreases in heat production. These results indicate that the PGE-induced hypothermia is not the result of a peripheral vasodilation induced by the direct action of PGE on the tail vascular smooth muscle but is a central nervous system-mediated response of the thermoregulatory system induced by PGE within the peritoneal cavity. Capsaicin injected subcutaneously induces a transient hypothermia in rats because of stimulation of the warm receptors. If administered peripherally in sufficient amounts, it is reputed to impair peripheral warm receptors so that they become desensitized to the hypothermic effects of capsaicin. We measured PGE-induced hypothermias in rats both before and after capsaicin desensitization at Ta of 26 degrees C. Before desensitization the hypothermia was -1.14 +/- 0.12 degrees C, whereas after capsaicin treatment the PGE-induced hypothermia was -0.34 +/- 0.17 degrees C. The biological effects of capsaicin are diverse; however, based on current thinking about the thermoregulatory effects of capsaicin desensitization, our results indicate that peripheral warm receptor pathways are in some manner implicated in the hypothermia induced by intraperitoneal PGE.

In Vitro Electrophysiologic Studies on Nasal Airway Receptors of the Rabbit

Rabbit nasal airway receptors were investigated electrophysiologically in vitro. Cold receptors, warm receptors, and mechanoreceptors were found in the nasal membrane. The cold receptors showed a maximum static discharge at 28°C, and the warm receptors at 38°C. These thermoreceptors were activated constantly at temperatures between 18°C and 40°C. The mechanoreceptors were seen to adapt rapidly to gentle mechanical stimulation and were activated easily by repeated stimuli. Air blown directly at the nasal membrane did not activate the mechanoreceptors. It was concluded that nasal airflow sensation is due mainly to the activation of cold or warm receptors in the nasal airway, rather than the stimulation of mechanoreceptors.

Respiratory responses to noxious and nonnoxious heating of skin in cats

Respiratory responses to increased skin temperatures were recorded in anesthetized cerebrate and in unanesthetized decerebrate cats. All were vagotomized, glomectomized, and paralyzed. Core body temperature and end-tidal Pco2 were kept constant with servoncontrollers. Stimulation of cutaneous nociceptors by heating the skin to 46 degrees C caused respiration to increase in both cerebrate and decerebrate cats. An even larger facilitation of respiration occurred when the skin temperature was elevated to 51 degrees C. However, respiration did not increase in either group of cats when the skin was heated to 41 degrees C to activate cutaneous warm receptors. The phenomenon of sensitization of nociceptors was observed. Spinal transection prevented all the respiratory responses to cutaneous heating. We conclude that noxious, but not nonnoxious, increases in skin temperature cause increases in respiratory output.