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PubMed2005

Repetitive transcranial magnetic stimulation of dorsolateral prefrontal cortex increases tolerance to human experimental pain.

Dorsolateral prefrontal cortex (DLPFCx) has been implicated in pain perception and in a pain modulation pathway. However, the precise participation of this region is not completely understood. The aim of this study was to evaluate whether 1 Hz rTMS of DLPFCx modifies threshold and tolerance in experimental pain. The effect of 1 Hz rTMS during 15 min at 100% motor threshold was tested in one hundred and eighty right-handed healthy volunteers, using a parallel-group stimulation design. The stimulation sites were right or left DLPFCx, right or left motor cortex, vertex or sham. rTMS was applied in two experimental contexts: (1) To evaluate its transitory effect (interference or facilitation) during cold pressor threshold (CPTh) and tolerance (CPTt) and (2) to evaluate its long-term effect by stimulating before CPTh, CPTt, pain heat thermal threshold, pain pressure threshold and tolerance. During rTMS of right DLPFCx, an increase in left hand CPTt (mean +/- SD; 17.63 s +/- 5.58 to 30.94 s +/- 14.84, P < 0.001) and in right hand CPTt (18.65 s +/- 6.47 to 26.74 s +/- 11.85, P < 0.001) were shown. No other stimulation site modified any of the pain measures during or after rTMS. These results show that 1 Hz rTMS of right DLPFCx has a selective effect by increasing pain tolerance and also sustains a right hemisphere preference in pain processing.

Adolescent↗
PubMed2025

GHSR suppression in neurons protects against aging-associated metabolic and cognitive impairments.

Aging is accompanied by progressive declines in metabolic and cognitive functions. Growth hormone secretagogue receptor (GHSR), a receptor for the gut hormone ghrelin, is highly expressed in neurons and plays a crucial role in metabolic regulation. We previously reported that aged global GHSR-ablated mice are lean and insulin-sensitive, and that neuronal GHSR-deleted mice (Syn1-cre;Ghsrf/f) completely prevent diet-induced obesity. However,&#xa0;the role of neuronal&#xa0;GHSR in metabolic and cognitive aging has not been elucidated. The current study aims to determine the roles of neuronal GHSR in aging metabolism and cognitive dysfunction. Syn1-cre;Ghsrf/f mice were subjected to cold stress, glucose- and insulin-tolerance tests, behavioral tests, and tissue analysis. Aging is accompanied by glycemic dysregulation and insulin resistance; old Syn1-cre;Ghsrf/f mice showed improved glucose tolerance and insulin sensitivity. Aging is associated with thermogenic impairment and cognitive decline; old Syn1-cre;Ghsrf/f mice showed better cold resistance and retained better recognition memory. Noticeably,&#xa0;there were&#xa0;increased expression of thermogenic makers (PGC1&#x3b1; and UCP1) and elevated sympathetic innervation markers (tyrosine hydroxylase and synaptophysin) in brown adipose tissue of old Syn1-cre;Ghsrf/f mice. Lastly, old Syn1-cre;Ghsrf/f mice exhibited decreased pro-inflammatory cytokines and increased neural plasticity-related markers (brain-derived neurotrophic factor, synaptophysin, and tyrosine hydroxylase) in metabolic and cognitive-relevant brain regions such as hypothalamus, cortex, and hippocampus. In conclusion, neuronal inhibition of GHSR promotes a healthy aging phenotype showing improved energy metabolism and cognitive function, which is likely contributed to the improved thermogenesis and insulin sensitivity, reduced inflammation, and restored neuronal plasticity.

Animals↗
PubMed2002

The absence of acute tolerance during remifentanil infusion in volunteers.

UNLABELLED: The development of acute opioid tolerance in humans remains controversial. We tested the hypothesis that continuous remifentanil infusion leads to rapid development of opioid tolerance. Twenty healthy male volunteers were enrolled onto a randomized, placebo-controlled, double-blinded, cross-over design study to receive a 3 h continuous infusion of remifentanil (0.08 microg x kg(-1) x min(-1)) or saline. Test procedures included determination of pain perception thresholds and pain tolerance thresholds to heat and cold and neuroselective sine wave constant current at 5 Hz and 250 Hz. Test procedures were performed at baseline and then repeated at 25, 55, 85, 115, and 160 min (heat/cold) and at 35, 65, 95, 125, and 170 min (electrical current) during infusion. No significant decrease of the pain threshold devolutions between 55 and 180 min after the start of infusion of remifentanil could be detected. In conclusion, no development of acute opioid tolerance was observed during constant remifentanil infusion of 3 h in volunteers. IMPLICATIONS: The opioid remifentanil was applied to 20 volunteers at a constant concentration for 3 h while pain thresholds to temperature and current were repeatedly assessed. Our aim was to study whether thresholds decrease over time because of the rapid development of opioid tolerance. No development of rapid opioid tolerance was observed.

Adult↗
PubMed1996

Arabidopsis mutants showing an altered response to vernalization.

Flowering in many plant species is accelerated by a long period of cold temperature, known as a vernalization period. This research investigates how this cold temperature signal is perceived by plant cells and the mechanism by which it influences the transition to flowering. Mutagenesis of the late-flowering, vernalization-responsive, Arabidopsis mutant, fca, has yielded five independent mutations (termed vrn mutations) conferring an altered vernalization response. Allelism tests showed that these mutations fall into at least three complementation groups defining three loci named VRN 1, 2 and 3. The vrn1 and vrn2 mutations did not affect the acclimation response as judged by expression of cold-induced transcripts and freezing tolerance assays. vrn1-1 affected the short-day vernalization response of Landsberg erecta and reduced the vernalization response of other late-flowering Arabidopsis mutants. The acceleration of flowering by GA3 was not affected by vrn1-1. The VRN 1 locus was mapped to chromosome 3.

Acclimatization↗
PubMed2002

The effect of laboratory-induced depressed mood state on responses to pain.

Some researchers have suggested that a depressed mood state is associated with alterations in responses to pain. The authors examined cognitive, behavioral, and affective responses of 75 randomly assigned participants to depressed, neutral, or elated mood state induction conditions and subjected them to the cold-pressor task. Because they were unsuccessful in inducing elated moods, the authors used only the data for the depressed and neutral states as they measured pain threshold, tolerance, and unpleasantness during the test. After the task, the authors measured sensory, affective, and evaluative responses to the cold-pressor pain, as well as the participants' catastrophizing ideation about the painful procedure. The depressed mood state group, compared with the neutral group, had significantly lower cold-pressor tolerance times and higher pain catastrophizing scores. These results support previous findings that a depressed mood state may be associated with alterations in some pain responses.

Adult↗
PubMed2003

CBL1, a calcium sensor that differentially regulates salt, drought, and cold responses in Arabidopsis.

Although calcium is a critical component in the signal transduction pathways that lead to stress gene expression in higher plants, little is known about the molecular mechanism underlying calcium function. It is believed that cellular calcium changes are perceived by sensor molecules, including calcium binding proteins. The calcineurin B-like (CBL) protein family represents a unique group of calcium sensors in plants. A member of the family, CBL1, is highly inducible by multiple stress signals, implicating CBL1 in stress response pathways. When the CBL1 protein level was increased in transgenic Arabidopsis plants, it altered the stress response pathways in these plants. Although drought-induced gene expression was enhanced, gene induction by cold was inhibited. In addition, CBL1-overexpressing plants showed enhanced tolerance to salt and drought but reduced tolerance to freezing. By contrast, cbl1 null mutant plants showed enhanced cold induction and reduced drought induction of stress genes. The mutant plants displayed less tolerance to salt and drought but enhanced tolerance to freezing. These studies suggest that CBL1 functions as a positive regulator of salt and drought responses and a negative regulator of cold response in plants.

Arabidopsis↗
PubMed1999

Safety of a trivalent live attenuated intranasal influenza vaccine, FluMist, administered in addition to parenteral trivalent inactivated influenza vaccine to seniors with chronic medical conditions.

We conducted a randomized, double-blind trial to evaluate the safety and tolerability of a live attenuated cold adapted trivalent intranasal influenza vaccine, FluMist, compared with intranasal placebo when given in addition to a licensed trivalent injected inactivated influenza vaccine (TIV). The study population consisted of persons 65 years of age and older with chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days post-vaccination, sore throat was reported on at least one day by 15% (15/100) of FluMist recipients compared with 2% (2/100) of intranasal placebo recipients (p = 0.001). No other reactogenicity symptom was statistically associated with receipt of FluMist. Among this group, FluMist was safe and well tolerated when administered with TIV.

Administration, Intranasal↗
PubMed1998

Hatchling painted turtles (Chrysemys picta) survive only brief freezing of their bodily fluids.

Neonatal painted turtles (Chrysemys picta) spend their first winter inside the shallow, subterranean nest cavity where they completed embryogenesis. Consequently, hatchlings at high latitudes may be exposed to ice and cold during the winter. This study was undertaken to determine how long hatchlings withstand freezing at temperatures slightly below 0 degree C because tolerance for freezing has been proposed to be the key to survival by overwintering animals. A thermocouple was glued to the carapace of each hatchling. The animal was dipped in water to provide a site of nucleation of ice and was then placed into a glass jar that was partially immersed in a circulating bath at -2 degrees C. Carapace temperature was monitored throughout the procedure. When a freezing exotherm was detected, timing of the freezing event began. Animals were maintained in a frozen state for 12-48 h prior to being warmed to room temperature. Of the 39 hatchlings, 22 did not survive, and mortality increased as the duration of freezing increased. Logistic regression indicates that no turtle would have survived in a frozen state for more than 54 h. These results indicate that hatchlings can survive only brief exposure to freezing of the body fluids. Thus, hatchlings cannot tolerate freezing during prolonged periods of cold.

Acclimatization↗
PubMed1998

HOS1, a genetic locus involved in cold-responsive gene expression in arabidopsis.

Low-temperature stress induces the expression of a variety of genes in plants. However, the signal transduction pathway(s) that activates gene expression under cold stress is poorly understood. Mutants defective in cold signaling should facilitate molecular analysis of plant responses to low temperature and eventually lead to the identification and cloning of a cold stress receptor(s) and intracellular signaling components. In this study, we characterize a plant mutant affected in its response to low temperatures. The Arabidopsis hos1-1 mutation identified by luciferase imaging causes superinduction of cold-responsive genes, such as RD29A, COR47, COR15A, KIN1, and ADH. Although these genes are also induced by abscisic acid, high salt, or polyethylene glycol in addition to cold, the hos1-1 mutation only enhances their expression under cold stress. Genetic analysis revealed that hos1-1 is a single recessive mutation in a nuclear gene. Our studies using the firefly luciferase reporter gene under the control of the cold-responsive RD29A promoter have indicated that cold-responsive genes can be induced by temperatures as high as 19 degrees C in hos1-1 plants. In contrast, wild-type plants do not express the luciferase reporter at 10 degrees C or higher. Compared with the wild type, hos1-1 plants are l ess cold hardy. Nonetheless, after 2 days of cold acclimation, hos1-1 plants acquired the same degree of freezing tolerance as did the wild type. The hos1-1 plants flowered earlier than did the wild-type plants and appeared constitutively vernalized. Taken together, our findings show that the HOS1 locus is an important negative regulator of cold signal transduction in plant cells and that it plays critical roles in controlling gene expression under cold stress, freezing tolerance, and flowering time.

Arabidopsis↗
PubMed2004

Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients: a single-center, double-blind, placebo-controlled, randomized crossover study.

OBJECTIVE: OPC-28326 is a selective alpha-adrenergic antagonist with preferential binding to the alpha(2C)-adrenergic receptor (alpha(2C)-AR) subtype. This study observed the effect of OPC-28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma. METHODS: The study was designed as a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of OPC-28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature. RESULTS: Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC-28326 40-mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC-28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC-28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug-related were reported more frequently with 40 mg OPC-28326 than with 10 mg OPC-28326 or with placebo, but none were serious or sustained. CONCLUSION: OPC-28326 at doses of 10 mg and 40 mg was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC-28326 suggests that selective alpha(2C)-AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.

Administration, Oral↗
PubMedDate not supplied

Tolerance limits of liver grafts with 30 minutes of warm ischemia to cold preservation in swine.

AIM: The aim of this study was to investigate the safe time limits of cold preservation in University of Wisconsin (UW) solution of liver grafts subjected to warm ischemia (WI) for 30 minutes from non-heart-beating donors (NHBDs). METHODS: The safe time limits were studied in a simple porcine orthotopic liver transplantation (LTx) model. In donors, livers were subjected to 30 minutes of WI and subsequent 6-hour (Group 1, n = 5), 10-hour (Group 2, n = 5), and 14-hour (Group 3, n = 3) cold preservation in UW solution. RESULTS: All 5 animals in Group 1 survived up to 7 days, the survey endpoint. In Group 2, only 2 animals survived to the same survey endpoint. All animals in Group 3 died within 12 hours. The 1-week survival rate of Group 1 was significantly higher than those of the other 2 groups. Group 1 showed a lower level of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) after LTx, less pathological damage, higher concentration of adenosine triphosphate (ATP), and higher microcirculation blood flux in the grafted liver tissue at 1 hour after reperfusion than the other 2 groups. CONCLUSIONS: It is concluded that about 6 hours is the safe time limit of cold preservation in UW solution for liver grafts from NHBDs subjected to WI for 30 minutes.

Adenosine↗
PubMed2001

Affective pictures processing, attention, and pain tolerance.

Two experiments were conducted to determine whether attention mediates the effects of affective distractors on cold pressor pain, or whether the cognitive processes of priming and appraisal best account for the effects. In Experiment I, 65 male respondents were exposed to either pleasant, neutral or unpleasant pictures selected from the International Affective Pictures System (IAPS). The cold-pressor test was administered simultaneously. Consistent with predictions based on priming and appraisal hypotheses, results revealed a linear trend across conditions, such that pain tolerance scores were higher as a function of picture pleasantness. A second study was conducted to examine the role of pain cues in the effects of negative affect on cold pressor pain. Thirty-nine male respondents were exposed to unpleasant pictures that either did or did not include pain-related material. Respondents who viewed pictures without pain cues tolerated the cold water for a longer period of time than respondents who viewed pictures that contained pain-related information. Priming and appraisal processes that might underlie the observed differences, and the type of affective distractors that could be meaningful for enhancing pain tolerance, are discussed.

Adolescent↗
PubMed2001

Cold adaptive thermogenesis in small mammals from different geographical zones of China.

The mechanisms of thermogenesis and thermoregulation were studied in the tree shrew (Tupaia belangeri) and greater vole (Eothenomys miletus) of the subtropical region, and Brandt's vole (Microtus brandti), Mongolian gerbil (Meriones unguiculatus), Daurian ground squirrel (Spermophilus dauricus) and plateau pika (Ochotona curzoniae) of the northern temperate zone. Resting metabolic rate (RMR) and non-shivering thermogenesis (NST) increased significantly in T. belangeri, E. miletus, M. brandti and M. unguiculatus after cold acclimation (4 degrees C) for 4 weeks. In T. belangeri, the increase in RMR and thermogenesis at liver cellular level were responsible for enhancing the capacity of enduring cold stress, and homeothermia was simultaneously extended. Stable body temperature in M. brandti, E. miletus, M. unguiculatus and O. curzoniae was maintained mainly through increase in NST, brown adipose tissue (BAT) mass and its mitochondrial protein content, and the upregulation of uncoupling protein (UCP1) mRNA, as well as enhancement of the activity of cytochrome C oxidase, alpha-glycerophosphate oxidase and T(4) 5'-deiodinase in BAT mitochondria. The RMR in O. curzoniae and euthermic S. dauricus was not changed, while NST significantly increased during cold exposure; the former maintained their stable body temperature and mass, while body temperature in the latter declined by 4.8 degrees C. The serum T(3) concentration or ratio of T(3)/T(4) in all the species was enhanced after cold acclimation. Results indicated that: (1) the adaptive mechanisms of T. belangeri residing in the subtropical region to cold are primarily by increasing RMR and secondly by increasing NST, and the mechanisms of thermogenesis are similar to those in tropical mammals; (2) in small mammals residing in northern regions, the adaptation to cold is chiefly to increase NST; (3) the mechanism of cold-induced thermogenesis in E. miletus residing in subtropical and high mountain regions is similar to that in the north; (4) a low RMR in warm environments and peak RMR and NST in cold environments enabled M. unguiculatus to tolerate a semi-desert climate; (5) O. curzoniae has unusually high RMR and high NST, acting mainly via increasing NST to adapt to extreme cold of the Qinghai-Tibet Plateau; (6) the adaptation of euthermic S. dauricus to cold is due to an increase in NST and a relaxed homeothermia; and lastly (7) the thyroid hormone is involved in the regulation of cold adaptive thermogenesis in all the species studied.

Adaptation, Physiological↗
PubMed2001

Interactive effects of the affect quality and directional focus of mental imagery on pain analgesia.

College students (25 men and 25 women) were randomly assigned (within sex) to each of the 4 factorial groups, based on manipulation of affect quality (positive vs. negative) and directional focus (internal vs. external) of mental imagery, and to a control group receiving no manipulation. Both imagery variables had a significant impact on pain tolerance and ratings during a cold-pressor test with positive affect and external imagery producing greater analgesia than their counterpart conditions. Positive affect imagery combined with external imagery resulted in the lowest reported pain amongst the groups. However, self-reported mood descriptors did not consistently parallel the pain tolerance and rating data. Likewise, although heart rate and skin potential responses increased during the cold pressor for the group as a whole, the only significant difference amongst the experimental groups was the relatively higher skin potential reactivity of the positive affect-external imagery group--possibly reflecting greater task engagement for this group. Seemingly, imagery in this situation operates primarily via cognitive, rather than via physiological mediators of the pain experience.

Adult↗
PubMed2004

Catastrophizing and pain sensitivity among chronic pain patients: moderating effects of sensory and affect focus.

BACKGROUND: Pain catastrophizing is a particularly harmful cognitive factor among patients with chronic pain, but little is known of mechanisms linking this factor to pain and disability. PURPOSE: The study examined whether attentional focus on sensory versus affective information about pain constitutes a pathway by which catastrophizing affects responses to painful stimuli. METHODS: Participants were 82 chronic pain patients assigned randomly to sensory focus, affect focus, or control conditions. They underwent cold pressors first prior to and then following an information focus manipulation, and they completed the Pain Catastrophizing Scale (PCS). RESULTS: Regressions produced significant Condition x PCS interaction effects on threshold and tolerance change from first to second cold pressor, such that PCS scores were significantly and negatively related to these changes in both sensory and affect focus conditions, but not in the control condition. Only a main effect for PCS scores emerged for self-reported pain changes. Solving regression equations for hypothetical PCS values (+- 1 SD from the mean) revealed that (a) high catastrophizers decreased threshold and tolerance in the affect focus condition and showed no appreciable changes in sensory focus and (b) low catastrophziers showed increases in threshold and tolerance in sensory focus, but no appreciable changes in affect focus. Further, the degree to which patients focused on emotions during pain partly mediated effects of PCS scores on threshold and tolerance changes. CONCLUSION: Catastrophizing about pain may affect pain severity and distress of chronic pain patients through a bias toward processing the most disturbing elements of a painful stimulus.

Adult↗
PubMed2006

Stress responsive DEAD-box helicases: a new pathway to engineer plant stress tolerance.

Abiotic stresses including various environmental factors adversely affect plant growth and limit agricultural production worldwide. Minimizing these losses is a major area of concern for all countries. Therefore, it is desirable to develop multi-stress tolerant varieties. Salinity, drought, and cold are among the major environmental stresses that greatly influence the growth, development, survival, and yield of plants. UV-B radiation of sunlight, which damages the cellular genomes, is another growth-retarding factor. Several genes are induced under the influence of various abiotic stresses. Among these are DNA repair genes, which are induced in response to the DNA damage. Since the stresses affect the cellular gene expression machinery, it is possible that molecules involved in nucleic acid metabolism including helicases are likely to be affected. The light-driven shifts in redox-potential can also initiate the helicase gene expression. Helicases are ubiquitous enzymes that catalyse the unwinding of energetically stable duplex DNA (DNA helicases) or duplex RNA secondary structures (RNA helicases). Most helicases are members of DEAD-box protein superfamily and play essential roles in basic cellular processes such as DNA replication, repair, recombination, transcription, ribosome biogenesis and translation initiation. Therefore, helicases might be playing an important role in regulating plant growth and development under stress conditions by regulating some stress-induced pathways. There are now few reports on the up-regulation of DEAD-box helicases in response to abiotic stresses. Recently, salinity-stress tolerant tobacco plants have already been raised by overexpressing a helicase gene, which suggests a new pathway to engineer plant stress tolerance [N. Sanan-Mishra, X.H. Pham, S.K. Sopory, N. Tuteja, Pea DNA helicase 45 overexpression in tobacco confers high salinity tolerance without affecting yield. Proc. Natl. Acad. Sci. USA 102 (2005) 509-514]. Presently the exact mechanism of helicase-mediated stress tolerance is not understood. In this review we have described all the reported stress-induced helicases and also discussed the possible mechanisms by which they can provide stress tolerance.

DNA Helicases↗
PubMed1988

Platelet and clotting activities after cold stress in diabetic patients.

Platelet and clotting abnormalities have been described in diabetes, but little is known about their relationship to daily stresses. In order to evaluate whether states of abnormal carbohydrate metabolism modify the hemostatic response to stress, 12 subjects with type I diabetes mellitus, 9 with type II, 7 with impaired glucose tolerance and 10 healthy controls were exposed to a cold pressor test. Plasma concentrations of beta-thromboglobulin (index of platelet activation) and of fibrinopeptide A (index of thrombin formation) were measured before and 15 minutes after forearm immersion in melting ice. Basal levels of both proteins were significantly elevated (p less than 0.02) in the combined group of patients with diabetes and impaired glucose tolerance. While in healthy controls cold exposure failed to modify plasma concentration of either protein, obvious changes occurred in the diabetic and impaired glucose tolerance groups. In the combined patients group, beta-thromboglobulin levels decreased from 1.37 +/- 0.44 nmol/l to 1.03 +/- 0.39 (mean +/- SD, p less than 0.01), after the cold test, possibly in consequence of enhanced vascular permeability; while fibrinopeptide A levels increased from 1.52 +/- 1.03 nmol/l to 3.45 +/- 4.19 (p less than 0.02). The degree and pattern of abnormalities observed in basal as well as stimulated levels of fibrinopeptide A differed somewhat among the three groups of patients. These studies indicate that, in the basal state, patients with diabetes or simple carbohydrate intolerance are more susceptible than controls to platelet activation and that after stress thrombin formation can occur although some variability exists among and within groups of patients. The consequences of such increased thrombotic activity may have a bearing on the pathogenesis of large vessel disease, a complication common to diabetes and impaired glucose tolerance.

Blood Coagulation↗