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David D Mckemy - One of the best experts on this subject based on the ideXlab platform.
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the molecular and cellular basis of Cold Sensation
ACS Chemical Neuroscience, 2013Co-Authors: David D MckemyAbstract:Of somatosensory modalities, Cold is one of the more ambiguous percepts, evoking the pleasant Sensation of cooling, the stinging bite of Cold pain, and welcome relief from chronic pain. Moreover, unlike the precipitous thermal thresholds for heat activation of thermosensitive afferent neurons, thresholds for Cold fibers are across a range of cool to Cold temperatures that spans over 30 °C. Until recently, how Cold produces this myriad of biological effects has been poorly studied, yet new advances in our understanding of Cold mechanisms may portend a better understanding of sensory perception as well as provide novel therapeutic approaches. Chief among these was the identification of a number of ion channels that either serve as the initial detectors of Cold as a stimulus in the peripheral nervous system, or are part of rather sophisticated differential expression patterns of channels that conduct electrical signals, thereby endowing select neurons with properties that are amenable to electrical signaling in the Cold. This review highlights the current understanding of the channels involved in Cold transduction as well as presents a hypothetical model to account for the broad range of Cold thermal thresholds and distinct functions of Cold fibers in perception, pain, and analgesia.
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how Cold is it trpm8 and trpa1 in the molecular logic of Cold Sensation
Molecular Pain, 2005Co-Authors: David D MckemyAbstract:Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful) temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP) family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermoSensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious Cold Sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the Sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in Cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious Cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in Cold Sensation needs to be confirmed. Thus, the molecular logic for the perception of Cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these Cold thermoreceptors, as well as address the current controversy regarding TRPA1 and Cold signaling.
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How Cold is it? TRPM8 and TRPA1 in the molecular logic of Cold Sensation.
Molecular Pain, 2005Co-Authors: David D MckemyAbstract:Recognition of temperature is a critical element of sensory perception and allows us to evaluate both our external and internal environments. In vertebrates, the somatosensory system can discriminate discrete changes in ambient temperature, which activate nerve endings of primary afferent fibers. These thermosensitive nerves can be further segregated into those that detect either innocuous or noxious (painful) temperatures; the latter neurons being nociceptors. We now know that thermosensitive afferents express ion channels of the transient receptor potential (TRP) family that respond at distinct temperature thresholds, thus establishing the molecular basis for thermoSensation. Much is known of those channels mediating the perception of noxious heat; however, those proposed to be involved in cool to noxious Cold Sensation, TRPM8 and TRPA1, have only recently been described. The former channel is a receptor for menthol, and links the Sensations provided by this and other cooling compounds to temperature perception. While TRPM8 almost certainly performs a critical role in Cold signaling, its part in nociception is still at issue. The latter channel, TRPA1, is activated by the pungent ingredients in mustard and cinnamon, but has also been postulated to mediate our perception of noxious Cold temperatures. However, a number of conflicting reports have suggested that the role of this channel in Cold Sensation needs to be confirmed. Thus, the molecular logic for the perception of Cold-evoked pain remains enigmatic. This review is intended to summarize our current understanding of these Cold thermoreceptors, as well as address the current controversy regarding TRPA1 and Cold signaling.
Michele Curatolo - One of the best experts on this subject based on the ideXlab platform.
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block of pinprick and Cold Sensation poorly correlate with relief of postoperative pain during epidural analgesia
The Clinical Journal of Pain, 1999Co-Authors: Michele Curatolo, Roselyne Kaufmann, Steen Petersenfelix, Lars Arendtnielsen, Pasquale Scaramozzino, A M ZbindenAbstract:OBJECTIVE: To test the following hypotheses: there is a correlation between spread of epidural analgesia as assessed postoperatively by pinprick/Cold test and postoperative pain intensity; block of pinprick/Cold Sensation is associated with absence of postoperative pain. DESIGN: Correlation analysis on prospectively collected data. SETTING: University hospital. PATIENTS: One hundred patients undergoing major surgery. Consecutive sample. INTERVENTIONS: Patients received an epidural infusion of bupivacaine 1 mg/ml, fentanyl 2 microg/ml, and epinephrine 2 microg/ml for at least 48 hours postoperatively. The infusion rate was adjusted according to pain intensity, occurrence of hypotension, or motor block. OUTCOME MEASURES: Assessments were made on three time points: 20-24 hours, 32-36 hours, and 4248 hours after extubation. Assessments included pinprick and Cold sensitivity from C2 to S5, pain intensity (visual analogue scale, VAS) at rest, after cough, and after mobilization. Data were analyzed by multiple regression. RESULTS: VAS significantly decreased with increasing spread (number of dermatomes for which hyposensitivity to pinprick or Cold was observed). Spread could explain only 2-5% of the variability of VAS. Absence of both pinprick and Cold Sensation at all dermatomes corresponding to the surgical wound was frequently associated with pain. A high proportion of patients manifesting an upper level of block above T5 had pain after abdominal surgery. CONCLUSIONS: Spread and efficacy of epidural analgesia as assessed by pinprick and Cold stimulation correlate poorly with postoperative pain. These methods are of limited value both as clinical indicators of the efficacy of postoperative pain control and for investigating the effect of epidural drugs and techniques.
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Spinal anaesthesia inhibits central temporal summation.
BJA: British Journal of Anaesthesia, 1997Co-Authors: Michele Curatolo, Steen Petersen-felix, Lars Arendt-nielsen, Alex M. ZbindenAbstract:In a previous investigation we found that extradural anaesthesia did not adequately inhibit temporal summation of repeated electrical stimuli: pain to repeated stimuli was blocked in only one of 10 patients, and pain thresholds to repeated stimuli were significantly lower than pain thresholds to a single stimulus. In this study we have investigated in 10 patients the effect of spinal anaesthesia on temporal summation, assessed by repeated electrical stimulation of the sural nerve. Plain 0.5% bupivacaine 18 mg was injected at L2-3. The pain threshold to a single electrical stimulus, summation threshold (increase in perception during repeated electrical stimuli with five impulses of the same intensity at 2 Hz), pinprick and Cold Sensation were assessed. After spinal anaesthesia, pain to both single and repeated stimulation, and pinprick and Cold Sensation, disappeared in all patients. We conclude that spinal anaesthesia inhibits temporal summation elicited by repeated electrical stimulation.
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Temporal summation during extradural anaesthesia
BJA: British Journal of Anaesthesia, 1995Co-Authors: Michele Curatolo, Steen Petersen-felix, Lars Arendt-nielsen, M. Fischer, Alex M. ZbindenAbstract:We have investigated in 10 patients the effect of extradural anaesthesia on temporal summation by comparing pain thresholds to single and repeated (five impulses at 2 Hz) electrical stimuli and compared these tests with pinprick and Cold stimulation. Bupivacaine 0.5% (20 ml) was injected at L2-3. After extradural anaesthesia the threshold to repeated stimuli was significantly lower than the threshold to single stimuli (P = 0.0007). Nine patients lost Cold Sensation and 10 patients pinprick Sensation. Pain to single electrical stimulation disappeared in six patients and pain to repeated electrical stimulation in one. Pain may be evoked by temporal summation of repeated electrical stimuli even when pinprick Sensation, Cold Sensation and pain to single electrical stimuli are inhibited. Thus temporal summation should be taken into consideration when extradural analgesia is assessed.
Ardem Patapoutian - One of the best experts on this subject based on the ideXlab platform.
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trpm8 is required for Cold Sensation in mice
Neuron, 2007Co-Authors: Ajay Dhaka, Amber N Murray, Jayanti Mathur, Taryn J Earley, Matt Petrus, Ardem PatapoutianAbstract:SUMMARY ThermoTRPs, a subset of the Transient Receptor Potential (TRP) family of cation channels, have been implicated in sensing temperature. TRPM8 and TRPA1 are both activated by cooling; however, it is unclear whether either ion channel is required for thermoSensation in vivo. We show that mice lacking TRPM8 have severe behavioral deficits in response to Cold stimuli. In thermotaxis assays of temperature gradient and two-temperature choice assays, TRPM8-deficient mice exhibit strikingly reduced avoidance of Cold temperatures. TRPM8deficient mice also lack behavioral response to Cold-inducing icilin application and display an attenuated response to acetone, an unpleasant Cold stimulus. However, TRPM8-deficient mice have normal nociceptive-like responses to subzero centigrade temperatures, suggesting the presence of at least one additional noxious Cold receptor.Finally,we show that TRPM8 mediates the analgesic effect of moderate cooling after administration of formalin, a painful stimulus. Therefore, depending on context, TRPM8 contributes to sensing unpleasant Cold stimuli or mediating the effects of Cold analgesia.
Christa Boer - One of the best experts on this subject based on the ideXlab platform.
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thermographic skin temperature measurement compared with Cold Sensation in predicting the efficacy and distribution of epidural anesthesia
Journal of Clinical Monitoring and Computing, 2018Co-Authors: Arnoud A Bruins, Kay R J Kistemaker, Annemieke Boom, John H G M Klaessens, Rudolf M Verdaasdonk, Christa BoerAbstract:Due to the high rates of epidural failure (3–32%), novel techniques are required to objectively assess the successfulness of an epidural block. In this study we therefore investigated whether thermographic temperature measurements have a higher predictive value for a successful epidural block when compared to the Cold Sensation test as gold standard. Epidural anesthesia was induced in 61 patients undergoing elective abdominal, thoracic or orthopedic surgery. A thermographic picture was recorded at 5, 10 and 15 min following epidural anesthesia induction. After 15 min a Cold Sensation test was performed. Epidural anesthesia is associated with a decrease in skin temperature. Thermography predicts a successful epidural block with a sensitivity of 54% and a PPV of 92% and a specificity of 67% and a NPV of 17%. The Cold Sensation test shows a higher sensitivity and PPV than thermography (97 and 93%), but a lower specificity and NPV than thermography (25 and 50%). Thermographic temperature measurements can be used as an additional and objective method for the assessment of the effectiveness of an epidural block next to the Cold Sensation test, but have a low sensitivity and negative predictive value. The local decrease in temperature as observed in our study during epidural anesthesia is mainly attributed to a core-to-peripheral redistribution of body heat and vasodilation.
Spyros Kollias - One of the best experts on this subject based on the ideXlab platform.
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the supraspinal neural correlate of bladder Cold Sensation an fmri study
Human Brain Mapping, 2011Co-Authors: Ulrich Mehnert, Lars Michels, Monikazita Zempleni, Brigitte Schurch, Spyros KolliasAbstract:In recent years, functional imaging studies have revealed a supraspinal network, which is involved in perception and processing of bladder distention. Very little information exists on the cortical representation of C-fiber transmitted temperature Sensation of the human bladder, although C-fibers seem to be involved in the pathomechanisms of bladder dysfunctions. Our aim was, therefore, to evaluate the outcome of bladder Cold stimulation on supraspinal activity using functional magnetic resonance imaging (fMRI). A block design fMRI study was performed in 14 healthy females at the MR-center of the University of Zurich. After catheterization, all subjects were investigated in a 3.0-Tesla Scanner. The scanning consisted of 10 repetitive cycles. Each cycle consisted of five conditions: REST, INFUSION, Sensation, DRAIN 1, and DRAIN 2. Cold saline was passively infused at 4-8 degrees C during scanning. Not more than 100 ml were infused per cycle. Blood-oxygen-level-dependent (BOLD) signal analysis of the different conditions was compared to REST. All activations were evaluated on a random effects level at P = 0.001. Activation of brain regions for bladder Cold stimulation (DRAIN 1 period) was found bilaterally in the inferior parietal lobe [Brodmann area (BA) 40], the right insula (BA 13), the right cerebellar posterior lobe, the right middle temporal gyrus (BA 20), and the right postcentral gyrus (BA 3). In conclusion, bladder cooling caused a different supraspinal activation pattern compared to what is known to occur during bladder distention. This supports our hypothesis that Cold Sensation is processed differently from bladder distension at the supraspinal level. Hum Brain Mapp, 2010. (c) 2010 Wiley-Liss, Inc.
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The supraspinal neural correlate of bladder Cold Sensation—An fMRI study
Human Brain Mapping, 2010Co-Authors: Ulrich Mehnert, Lars Michels, Monikazita Zempleni, Brigitte Schurch, Spyros KolliasAbstract:In recent years, functional imaging studies have revealed a supraspinal network, which is involved in perception and processing of bladder distention. Very little information exists on the cortical representation of C-fiber transmitted temperature Sensation of the human bladder, although C-fibers seem to be involved in the pathomechanisms of bladder dysfunctions. Our aim was, therefore, to evaluate the outcome of bladder Cold stimulation on supraspinal activity using functional magnetic resonance imaging (fMRI). A block design fMRI study was performed in 14 healthy females at the MR-center of the University of Zurich. After catheterization, all subjects were investigated in a 3.0-Tesla Scanner. The scanning consisted of 10 repetitive cycles. Each cycle consisted of five conditions: REST, INFUSION, Sensation, DRAIN 1, and DRAIN 2. Cold saline was passively infused at 4-8 degrees C during scanning. Not more than 100 ml were infused per cycle. Blood-oxygen-level-dependent (BOLD) signal analysis of the different conditions was compared to REST. All activations were evaluated on a random effects level at P = 0.001. Activation of brain regions for bladder Cold stimulation (DRAIN 1 period) was found bilaterally in the inferior parietal lobe [Brodmann area (BA) 40], the right insula (BA 13), the right cerebellar posterior lobe, the right middle temporal gyrus (BA 20), and the right postcentral gyrus (BA 3). In conclusion, bladder cooling caused a different supraspinal activation pattern compared to what is known to occur during bladder distention. This supports our hypothesis that Cold Sensation is processed differently from bladder distension at the supraspinal level. Hum Brain Mapp, 2010. (c) 2010 Wiley-Liss, Inc.