Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets.     

Effect of cold acclimation on antioxidant status in cold acclimated skaters

We investigated whether cold acclimation leads to increased activity of the antioxidant defense enzymes and muscle injury. Comparisons were between short track skaters (n=6) and inline skaters (n=6) during rest and at submaximal cycling (65% VO2max) in cold (ambient temperature: 5+/-1 degrees C, relative humidity: 41+/-8%) and warm conditions (ambient temperature: 21+/-1 degrees C, relative humidity: 35+/-5%), during 60 min, respectively, and during the recovery phase. Erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHpx), reduced glutathione (GSH), thiobarbituric substance acid (TBARS), serum creatine kinase (CK), lactate dehydrogenase (LDH), plasma myoglobin (Mb) and cortisol were determined. Activities of CAT and GSHpx and the level of GSH and TBARS in erythrocyte and the level of LDH in serum were elevated in cold acclimated subjects. We suggested that the compensatory increase in antioxidative defense enzymes resulting from long-term cold exposure may reflect the elevated reactive oxygen species (ROS) production and muscle injury at this environment acclimation.     

冷受体TRPM8在冷感知中的作用和调节

感觉体内外温度变化是生物与生俱来的能力之一,可有效调节机体体温,参与防御反应和减少自身损伤等.瞬时受体电位melastatin 8(transient receptor potential melastatin 8,TRPM8)是机体重要的一种冷受体,它的缺乏使动物对冷的敏感性减弱,对冷物质模拟物如薄荷醇和冰片等反应能力降低.TRPM 8的活性受细胞膜电位和膜脂的影响,它参与了体温调节和痛觉反应等.这些研究一方面有助于帮助理解机体对冷的感知机理,另一方面也使TRPM8有望成为新的药物作用靶点.     

Heat debt during cold air exposure before and after cold water immersions

Acclimation to cold can manifest itself in several different ways, insulative and metabolic being the most common. Bittel (J. Appl. Physiol. 62: 1627-1634, 1987) has demonstrated that heat debt, which encompasses both heat production and heat loss, can be used as a unitary index of acclimation. However, conflicting results are obtained if heat debt is calculated using a mean-weighted body temperature (Tb) vs. the change of body heat content through the integration of heat storage (S). The present study examines the determination of heat debt by three methods of calculation, the first based on Tb and the other two based on S where heat losses are measured in one and predicted in the other. Data were obtained from five healthy young males exposed to 10 degrees C air for 2 h on four different occasions. The first two exposures provided control data, while the last two were performed after 5 and 10 days, respectively, of daily immersions in 15 degrees C water to induce acclimation. The variability in response between the control exposures was as large as that among the other exposures. Although the method of calculation using Tb indicated that subjects were close to a thermal balance after 2 h of cold air exposure, this contrasted sharply with the result of the other two methods that indicated heat debt was still increasing steadily. The latter two methods are considered more accurate for transient heat debt calculation. Although cases of individual acclimation were found, these were different among the subjects, resulting in pooled responses that indicated no group acclimation by means of any of the three methods of calculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonshivering thermogenesis and cold resistance in rats under severe cold conditions.

Following either chronic exposure to 6 degrees C, or outdoor winter exposure, or chronic treatment with tyramine rats were exposed to -40 degrees C and their oxygen consumption and colonic temperature monitored. Fall in body temperature with time of exposure followed a sigmoid curve which had an inflection point around 32.9 degrees C. Both the time required for body temperature to reach this point and hypothermic resistance defined as the total O2 consumed up to the inflection time were useful indices of resistance to severe cold; Three days before the cold tests, capacity for norepinephrine-induced nonshivering thermogenesis was measured in all animals by examination of their metabolic response to tyraminemthe magnitude of response to tyramine correlated well with hypothermic resistance only for those rats chroncally treated with tyramine. It is concluded that it is impossible to predict with any reasonable degree of confidence the cold resistance of a rat from its tyramine response. In cold-acclimated rats, factors in addition to norepinephrine sensitivity are significantly involved in cold resistance and deserve further studies.     

Effects of repeated short-term cold exposures on cold induced thermogenesis of women

The effects of repeated exposures to resting cold air (10°C) on the shivering and thermogenic responses of women to standard cold stress were investigated. Ten women, aged 18 to 34 years, were divided into two groups of five women each. One group, the acclimated (A) was exposed ten times within 2 weeks, the first and the last exposures being the pre-and post-tests respectively. The second group, the control (C) was exposed twice within 18 days. Measurements of rectal and skin temperatures, oxygen uptake, time to onset of shivering (TOS), and perceived cold were performed during all exposures. Shivering responses were evaluated by electromyography and visually. A significant (P<0.05), increase was seen in TOS (from 26.2 min to 55.6 min), and a significant decrease was seen in thermoregulatory heat production (from 14.78 kcal/h to –2.64 kcal/h) in group A; these changes were evident after about five exposures. It is concluded that the women became cold acclimated as a result of the repeated short-term resting cold air exposures.Research supported by Capes/Brazil, and by the Universidade Federal de Minas Gerais/Brazil     

Metabolomic profiling of rapid cold hardening and cold shock in Drosophila melanogaster

A short exposure to a mild cold stress is sufficient to increase cold tolerance in many insects. This phenomenon, termed rapid cold hardening (RCH) expands the thermal interval that can be exploited by the insect. To investigate the possible role of altered metabolite levels during RCH, the present study used untargeted (1)H NMR metabolomic profiling to examine the metabolomic response in Drosophila melanogaster during the 72 h following RCH and cold shock treatment. These findings are discussed in relation to the costs and benefits of RCH that are measured in terms of survival and reproductive output. Cold shock caused a persistent disturbance of the metabolite profile that correlated well with a delayed onset of cold shock mortality. The disruption of metabolite homeostasis was smaller following RCH, where control levels were fully recovered after 72 h. RCH improved both survival and reproductive output after a subsequent cold shock but the RCH treatment alone was associated with costs in terms of reduced survival and reproductive output. The most pronounced changes following the RCH treatment were elevated levels of glucose and trehalose. Although, it is difficult to discern if a change in a specific metabolite is linked to physiological processes of adaptive, neutral or detrimental nature we observed that the onset and magnitude of the increased sugar levels correlated tightly with the improved chill tolerance following RCH. These findings suggest a putative role of cryoprotectants during RCH which are discussed in the light of the existing literature on the mechanistic background of RCH.     

Effect of photoperiod and cold acclimation on survival of mice in cold

Male albino mice (Swiss-Webster) were raised at 5 °C under short (8L:16D) and long (16L:8D) light periods. All mice were housed in groups of three to five individuals in plastic mouse cages (16 × 12 × 28 cm) until 42 days of age with food and water ad libitum and cold exposed to ?40 °C between 10:00 am and 4:00 pm to determine survival time or time until loss of righting response occurred (CT min). Under short photo-periods, survival time was 49.3 ± 4.4 min and under long photoperiods it was 38.7 ± 1.9 min (P < 0.05). A second group of mice was maintained from birth at thermoneutral temperature (22 °C) under constant darkness, short day lengths (4L:20D), or constant light in the same fashion as mentioned above. When exposed to ?20 °C survival time was found to be 80.0 ± 5.0 min for the animals kept in constant darkness, 61.1 ± 2.3 min for animals raised in short photo-periods (4L:20D) (P < 0.01), and 52.4 ± 2.3 min for mice raised in constant light (P < 0.05). After 30 min mean rectal temperature was 32.1 ± 0.47 °C for constant-darkness animals, 30.5 ± 0.43 °C for short-day animals (P < 0.02), and 28.5 ± 0.74 °C for animals raised in constant light (P < 0.05). After 60 min mean rectal temperatures for constant-dark, 4L:20D, and constant-light animals were compared and body temperature was found to be 23.7 ± 1.6, 17.3 ± 1.5 (P < 0.01), and 12.8 ± 0.87 °C (P < 0.05), respectively. From these data, it is obvious that photoperiod influences cold resistance at both cold and thermoneutral acclimation temperatures although when considered individually, cold acclimation enhances cold survival to a greater degree than does reduced light exposure.