scholarly journals A core signaling mechanism at the origin of animal nociception

2017 ◽  
Author(s):  
Oscar M. Arenas ◽  
Emanuela E. Zaharieva ◽  
Alessia Para ◽  
Constanza Vásquez-Doorman ◽  
Christian P. Petersen ◽  
...  
Keyword(s):  
Heat Exposure ◽  
Oxygen Species ◽  
Common Ancestry ◽  
Protective Behavior ◽  
Noxious Heat ◽  
Signaling Mechanism ◽  
Early Markers ◽  
Core Function ◽  
Noxious Stimuli ◽  
Escape Behaviors

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that a remarkably conserved signaling mechanism mediates the detection of noxious stimuli in animals as diverse as flatworms and humans. Planarian flatworms are amongst the simplest bilateral animals with a centralized nervous system, and capable of directed behavior. We demonstrate that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant fruit flies (Drosophila) are also defective in the avoidance of noxious heat 1-3. Unexpectedly, we find that either the planarian or the human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that human nociceptive systems may share a common ancestry with those of most extant animals, tracing back their origin to a progenitor that lived more than 500 million years ago.

scholarly journals Nociceptive interneurons control modular motor pathways to promote escape behavior in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anita Burgos ◽  
Ken Honjo ◽  
Tomoko Ohyama ◽  
Cheng Sam Qian ◽  
Grace Ji-eun Shin ◽  
...  
Keyword(s):  
Escape Behavior ◽  
Nociceptive Behavior ◽  
Electron Microscopic ◽  
Noxious Heat ◽  
Sensory Stimuli ◽  
Motor Pathways ◽  
Motor Circuits ◽  
Drosophila Larvae ◽  
Noxious Stimuli ◽  
Escape Behaviors

Rapid and efficient escape behaviors in response to noxious sensory stimuli are essential for protection and survival. Yet, how noxious stimuli are transformed to coordinated escape behaviors remains poorly understood. In Drosophila larvae, noxious stimuli trigger sequential body bending and corkscrew-like rolling behavior. We identified a population of interneurons in the nerve cord of Drosophila, termed Down-and-Back (DnB) neurons, that are activated by noxious heat, promote nociceptive behavior, and are required for robust escape responses to noxious stimuli. Electron microscopic circuit reconstruction shows that DnBs are targets of nociceptive and mechanosensory neurons, are directly presynaptic to pre-motor circuits, and link indirectly to Goro rolling command-like neurons. DnB activation promotes activity in Goro neurons, and coincident inactivation of Goro neurons prevents the rolling sequence but leaves intact body bending motor responses. Thus, activity from nociceptors to DnB interneurons coordinates modular elements of nociceptive escape behavior.

scholarly journals Ascorbate-Dependent Peroxidase (APX) from Leishmania amazonensis Is a Reactive Oxygen Species-Induced Essential Enzyme That Regulates Virulence

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
Lucia Xiang ◽  
Maria Fernanda Laranjeira-Silva ◽  
Fernando Y. Maeda ◽  
Jason Hauzel ◽  
Norma W. Andrews ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Macrophage Infection ◽  
Cutaneous Lesions ◽  
Signaling Mechanism ◽  
Content Type ◽  
Temporal Regulation ◽  
Metacyclic Promastigotes

ABSTRACT The molecular mechanisms underlying biological differences between two Leishmania species that cause cutaneous disease, L. major and L. amazonensis, are poorly understood. In L. amazonensis, reactive oxygen species (ROS) signaling drives differentiation of nonvirulent promastigotes into forms capable of infecting host macrophages. Tight spatial and temporal regulation of H2O2 is key to this signaling mechanism, suggesting a role for ascorbate-dependent peroxidase (APX), which degrades mitochondrial H2O2. Earlier studies showed that APX-null L. major parasites are viable, accumulate higher levels of H2O2, generate a greater yield of infective metacyclic promastigotes, and have increased virulence. In contrast, we found that in L. amazonensis, the ROS-inducible APX is essential for survival of all life cycle stages. APX-null promastigotes could not be generated, and parasites carrying a single APX allele were impaired in their ability to infect macrophages and induce cutaneous lesions in mice. Similar to what was reported for L. major, APX depletion in L. amazonensis enhanced differentiation of metacyclic promastigotes and amastigotes, but the parasites failed to replicate after infecting macrophages. APX expression restored APX single-knockout infectivity, while expression of catalytically inactive APX drastically reduced virulence. APX overexpression in wild-type promastigotes reduced metacyclogenesis, but enhanced intracellular survival following macrophage infection or inoculation into mice. Collectively, our data support a role for APX-regulated mitochondrial H2O2 in promoting differentiation of virulent forms in both L. major and L. amazonensis. Our results also uncover a unique requirement for APX-mediated control of ROS levels for survival and successful intracellular replication of L. amazonensis.

Physiological Properties of the Lamina I Spinoparabrachial Neurons in the Rat

2000 ◽  
Vol 83 (4) ◽  
pp. 2239-2259 ◽  
Author(s):  
Hervé Bester ◽  
Victoria Chapman ◽  
Jean-Marie Besson ◽  
Jean-François Bernard
Keyword(s):  
Great Majority ◽  
Noxious Heat ◽  
Stimulus Response ◽  
Lamina I ◽  
C Fibers ◽  
Control Response ◽  
The Mean ◽  
Noxious Stimuli ◽  
The Individual ◽  
Almost All

Single-unit extracellular recordings of spino-parabrachial (spino-PB) neurons ( n = 53) antidromically driven from the contralateral parabrachial (PB) area were performed in the lumbar cord in anesthetized rats. All the spino-PB neurons were located in the lamina I of the dorsal horn. Their axons exhibited conduction velocities between 2.8 and 27.8 m/s, in the thin myelinated fibers range. They had an extremely low spontaneous activity (median = 0.064 Hz) and a small excitatory receptive field (≤2 toes or pads). They were all activated by both peripheral A (mainly Aδ) and C fibers after intense transcutaneous electrical stimulation. Their discharge always increased in response to noxious natural stimuli of increasing intensities. The great majority (75%) of spino-PB neurons were nociceptive specific, i.e., they were excited only by noxious stimuli. The remaining (25%) still were excited primarily by noxious stimuli but also responded moderately to innocuous stimuli. Almost all spino-PB neurons (92%, 49/53) were activated by both mechanical and heat noxious stimuli. Among them, 35% were in addition moderately activated by noxious cold (thresholds between +20 and −10°C). Only (8%, 4/53) responded exclusively to noxious heat. Spino-PB neurons clearly encoded the intensity of mechanical ( n = 39) and thermal ( n = 38) stimuli in the noxious range, and most of the individual stimulus-response functions were monotonic and positive up to 40/60 N · cm−2 and 50°C, respectively. For the mechanical modality, the mean threshold was 11.5 ± 1.25 N · cm−2 (mean ± SE), the response increased almost linearly with the logarithm of the pressure between 10 and 60 N · cm−2, the mean p 50(pressure evoking 50% of the maximum response) and the maximum responsiveness were: 30 ± 2.4 N · cm−2 and 40.5 ± 5 Hz, respectively. For the thermal modality, the mean threshold was 43.6 ± 0.5°C, the mean curve had a general sigmoid aspect, the steepest portion being in the 46–48°C interval, the mean t 50 and the maximum responsiveness were: 47.4 ± 0.3°C and 40 ± 4.4 Hz, respectively. Most of the spino-PB neurons tested (13/16) had their noxiously evoked responses clearly inhibited by heterotopic noxious stimuli. The mean response to noxious stimuli during heterotopic stimuli was 31.7 ± 6.1% of the control response. We conclude that the nociceptive properties of the lamina I spino-PB neurons are reflected largely by those of PB neurons that were suggested to be involved in autonomic and emotional/aversive aspects of pain.

scholarly journals Stepwise increasing sequential offsets cannot be used to deliver high thermal intensities with little or no perception of pain

2019 ◽  
Vol 122 (2) ◽  
pp. 729-736
Author(s):  
Stuart W. G. Derbyshire ◽  
Victoria Jane En Long ◽  
Christopher L. Asplund
Keyword(s):  
Low Temperature ◽  
Stimulus Intensity ◽  
Pain Perception ◽  
Noxious Heat ◽  
Pain Experience ◽  
Analgesic Effects ◽  
Heat Stimulus ◽  
Long Duration ◽  
Pain Ratings ◽  
Noxious Stimuli

Offset analgesia (OA) is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. Forty-eight participants continuously rated their pain experience during trials containing trains of heat stimuli delivered by Peltier thermode. Stimuli were adjusted through either stepwise sequential increases of 2°C and decreases of 1°C or direct step increases of 1°C up to a maximum of 46°C. Step durations (1, 2, 3, or 6 s) varied by trial. Pain ratings generally followed presented temperature, regardless of step condition or duration. For 6-s steps, OA was observed after each decrease, but the overall pain trajectory was unchanged. We found no evidence that sequential offsets could allow for little pain perception during noxious temperature presentation. NEW & NOTEWORTHY Offset analgesia is the disproportionate decrease in pain experience following a slight decrease in noxious heat stimulus intensity. We tested whether sequential offsets would allow noxious temperatures to be reached with little or no perception of pain. We found little evidence of such overall analgesia. In contrast, we observed analgesic effects after each offset with long-duration stimuli, even with relatively low-temperature noxious stimuli.

Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli

1980 ◽  
Vol 43 (6) ◽  
pp. 1594-1614 ◽  
Author(s):  
D. R. Kenshalo ◽  
G. J. Giesler ◽  
R. B. Leonard ◽  
W. D. Willis
Keyword(s):  
Receptive Fields ◽  
Dorsal Column ◽  
Sensory Cortex ◽  
Noxious Stimulation ◽  
Mechanical Stimuli ◽  
Thalamic Neuron ◽  
Noxious Heat ◽  
Thalamic Neurons ◽  
Noxious Stimuli ◽  
Stimulation Of

1. Recordings were made from the caudal part of the ventral posterior lateral (VPLc) nucleus of the thalamus in anesthetized macaque monkeys. In additon to many neurons that responded only to weak mechanical stimuli, scattered neurons were found that responded to both innocuous and noxious stimulation or just to noxious stimulation of the skin. A total of 73 such neurons were examined in 26 animals. 2. Noxious stimuli included strong mechanical stimuli (pressure, pinch, and squeezing with forceps) and graded noxious heat (from 35 degrees C adapting temperature to 43, 45, 47, and 50 degrees C). The responses of the VPLc neurons increased progressively with greater intensities of noxious stimulation. The stimulus-response function when noxious heat stimuli were used was a power function with an exponent greater than one. 3. Repetition of the noxious heat stimuli revealed sensitization of the responses of the thalamic neurons to such stimuli. The threshold for a response to noxious heat was lowered, and the responses to supra-threshold noxious heat stimuli were enhanced. 4. The responses of VPLc neurons to noxious heat stimuli adapted after reaching a peak discharge frequency. The rate of adaptation was slower for a stimulus of 50 degrees C than for one of 47 degrees C. 5. For the six neurons tested, responses to noxious heat were dependent on pathways ascending in the ventral part of the lateral funiculus contralateral to the receptive field (ipsilateral to the thalamic neuron). In two cases, the input to the thalamic neurons from axons of the dorsal column was also conveyed by way of a crossed pathway in the opposite ventral quadrant. In another case, access to the thalamic neuron by way of ascending dorsal column fibers was demonstrated. 6. The thalamic neurons had restricted contralateral receptive fields that were somatotopically organized. Neurons with receptive fields on the hindlimb were in the lateral part of the VPLc nucleus, whereas neurons with receptive fields on the forelimb were in medial VPLc. 7. Ninety percent of the VPLc neurons tested that responded to noxious stimuli could be activated antidromically by stimulation of the surface of SI sensory cortex. It was possible to confirm that many of these cells project to the SI sensory cortex by using microstimulation. Successful microstimulation points were either within the SI cortex or in the white matter just beneath the cortex. 8. We conclude that some neurons in the VPLc nucleus are capable of signaling noiceptive stimuli. The nociceptive information appears to reach these cells through the ventral part of the lateral funiculus on the side contralateral to the receptive field, presumably by way of the spinothalamic tract. The VPLc cells are somatotopically organized, and they are thalamocortical neurons that project to the VPLc nucleus and SI cortex play a role in nociception.

scholarly journals Temperature-dependence of mitochondrial function and production of reactive oxygen species in the intertidal mud clam Mya arenaria

2002 ◽  
Vol 205 (13) ◽  
pp. 1831-1841 ◽  
Author(s):  
D. Abele ◽  
K. Heise ◽  
H. O. Pörtner ◽  
S. Puntarulo
Keyword(s):  
Reactive Oxygen Species ◽  
Heat Stress ◽  
Heat Exposure ◽  
Reactive Oxygen ◽  
Mya Arenaria ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Ros Formation ◽  
Proton Leakage ◽  
Intertidal Population

SUMMARY Mitochondrial respiration, energetic coupling to phosphorylation and the production of reactive oxygen species (ROS) were studied in mitochondria isolated from the eurythermal bivalve Mya arenaria (Myoidea) from a low-shore intertidal population of the German Wadden Sea. Measurements were conducted both within the range of the habitat temperatures (5-15 °C) and when subjected to heat exposure at 20 °C and 25 °C. Experimental warming resulted in an increase in the rate of state 3 and state 4 respiration in isolated mitochondria. The highest respiratory coupling ratios (RCR) were found at 15 °C; at higher temperatures mitochondrial coupling decreased,and release of ROS doubled between 15 and 25 °C. ROS production was 2-3%of total oxygen consumption in state 3 (0.3-0.5 nmol ROS mg-1protein min-1) at the habitat temperature, reaching a maximum of 4.3 % of state 3 respiration and 7 % of oligomycin-induced state 4+respiration under heat stress. Thus, state 4 respiration, previously interpreted exclusively as a measure of proton leakage, included a significant contribution from ROS formation in this animal, especially under conditions of heat stress. Oxygen radical formation was directly dependent on temperature-controlled respiration rates in states 3 and 4 and inversely related to mitochondrial coupling (RCR+) in state 4. Mitochondrial ROS formation is therefore involved in cellular heat stress in this eurythermal marine ectotherm.

Parabrachial area: electrophysiological evidence for an involvement in cold nociception

1996 ◽  
Vol 75 (5) ◽  
pp. 2099-2116 ◽  
Author(s):  
L. Menendez ◽  
H. Bester ◽  
J. M. Besson ◽  
J. F. Bernard
Keyword(s):  
Receptive Fields ◽  
The Body ◽  
Maximal Response ◽  
Strong Response ◽  
Noxious Heat ◽  
Cold Stimulation ◽  
C Fibers ◽  
Cold Sensitive ◽  
The Mean ◽  
Noxious Stimuli

1. Thirty-five percent of 120 neurons recorded extracellularly in the parabrachial (PB) area of anesthetized rats responded to a peripheral cold stimulus (0 degrees C). The cold-sensitive neurons were located in the lateral PB area, and most of those exhibiting a strong response to cold stimuli were inside or in close vicinity to the area receiving a high density of projections from superficial neurons of the dorsal horn. 2. The receptive fields for cold stimulation often were restricted to one or two parts of the body with a contralateral predominance for the limbs. No side predominance was observed for the face. 3. From a low spontaneous activity (10th percentile < median < 90th percentile: 0.1 < 1.5 < 5 Hz), the PB neurons responded to cold noxious stimuli (0 degree C water bath or waterjet, 20 s), without observable delay, with a sustained discharge. The mean maximal response to the stimulus was 16.1 +/- 1.2 Hz (mean +/- SE; n = 42). 4. About one-half (45%) of these cold-sensitive neurons were activated specifically by cold stimulation and did not respond or were inhibited by noxious heat and/or pinch. The remaining (55%) cold-sensitive neurons were also driven by heat and/or pinch. 5. The cold-sensitive neurons exhibited a clear capacity to encode cold stimuli in the noxious range: the stimulus-response function was always positive and monotonic from 30 to 0 degrees C; the mean curve was linear between 20 and 0 degrees C before plateauing between 0 to -10 degrees C; the mean threshold to cold stimulation was 17.1 +/- 1 degrees C (n = 21) and the mean t50 was 10.7 +/- 1.1 degrees C (n = 13). 6. The cold-sensitive neurons responded to intense transcutaneous electrical stimulation with an early and/or a late peak of activation, the latencies of which were in the 15-50 ms and 80-170 ms ranges (n = 8), respectively, i.e., compatible with the activation of A delta and C fibers. Interestingly, the cold-specific neurons predominantly responded with a late peak, suggesting these neurons were primarily driven by peripheral C fibers. 7. The intravenous injection of morphine depressed the responses of PB neurons to cold noxious stimuli in a dose-related (1, 3, and 9 mg/kg) and naloxone reversible fashion. The ED50 value was estimated approximately 2 mg/kg. Furthermore, two populations of neurons could be separated according to their morphine sensitivity. 8. It is concluded that PB cold-nonspecific neurons could be involved in affective-emotional, autonomic and neuroendocrine reactions in response to noxious cold events. The PB cold-specific neurons could be, in addition, involved in some thermoregulatory processes.

Characterization of Heat Exposure‐Associated Escape Behaviors and HSP Gene Expression in Bed Bugs ( Cimex lectularius L.)

2021 ◽  
Author(s):  
Aaron R. Ashbrook ◽  
Jeffery L. Feder ◽  
Michael E. Scharf ◽  
Gary W. Bennett ◽  
Ameya D. Gondhalekar
Keyword(s):  
Gene Expression ◽  
Heat Exposure ◽  
Cimex Lectularius ◽  
Bed Bugs ◽  
Escape Behaviors
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