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.     

TLV in cold environments

1. 1. The risks encountered during cold exposure are general body cooling or local cooling of parts of th body.

2. 2. Measures of cold stress must account for the effects of climate, clothing and metabolic heat production on heat balance.

3. 3. The combinaed effect of air temperature, mean radiant temperature, humidity and air velocity determines the cooling power of the environment.

4. 4. The cooling power can be easily converted into a required insulation value (IREQ) for whole body heat balance.

5. 5. Extensive cooling of hands and feet may be a limiting factor, even when sufficient total insulation is provided. In addition the cooling effect of wind on unprotected skin must be considered.

6. 6. Recommendation regarding acceptable exposures can be expressed as lowest ambient temperatures and time limits as function of available protection and activity level, with due attention to both general and local effects.

Hemoproteins in the cold

This review highlights some aspects of the biochemistry of cold-adapted hemoproteins in fish and bacteria, without claiming to be exhaustive. Heme hexacoordination where the sixth ligand is provided by an internal amino-acid residue, in cold-adapted hemoproteins will be discussed.     

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.     

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.     

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.     

Work in artificial cold environments

The physiological characteristics of work in cold stores, as a typical artificial cold environment, are reviewed mainly from our various field and experimental studies. There are about 4,000 cold stores in Japan, and 85% of them are kept at temperatures below -20 degrees C. Although the duration of cold exposure per stay in a cold store was very short, forklift workers entered the cold stores very frequently. Cold stress and the decrease in workers' performance were the same as for continuous exposure to cold. Since the peripheral skin temperature of subjects at night is higher than that in the afternoon, they are less likely to feel cold or pain sensation at night. However, there was a marked decrease in rectal temperature and in manual performance. There is an increased risk of both hypothermia and accidents for those who work at night. The cold store workers, however, had adapted to cold through daily repeated cold exposures.     

Plants in a cold climate

Plants are able to survive prolonged exposure to sub-zero temperatures; this ability is enhanced by pre-exposure to low, but above-zero temperatures. This process, known as cold acclimation, is briefly reviewed from the perception of cold, through transduction of the low-temperature signal to functional analysis of cold-induced gene products. The stresses that freezing of apoplastic water imposes on plant cells is considered and what is understood about the mechanisms that plants use to combat those stresses discussed, with particular emphasis on the role of the extracellular matrix.