Strychnine Alters Response Properties of Trigeminal Nociceptive Neurons in the Rat

2001 ◽  
Vol 86 (6) ◽  
pp. 3069-3072 ◽  
Author(s):  
Catherine Ressot ◽  
Valerie Collado ◽  
Jean-Louis Molat ◽  
Radhouane Dallel
Keyword(s):  
Glycine Receptor ◽  
Mechanical Stimuli ◽  
Spinal Trigeminal Nucleus ◽  
Nociceptive Neurons ◽  
Air Jet ◽  
Low Threshold ◽  
Sensory Processes ◽  
Flow Of Information ◽  
Dose Dependent

The purpose of this study was to examine the role of glycine in sensory processes in the spinal trigeminal nucleus oralis (Sp5O). We evaluated the effect of intravenous administration of strychnine, a glycine receptor antagonist, on the responses of Sp5O convergent neurons evoked by innocuous peripheral electrical and mechanical stimuli in halothane-anesthetized rats. Strychnine significantly increased the Aβ-fiber–evoked activities of Sp5O neurons to electrical stimulation in a dose-dependent (0.2–0.8 mg/kg) fashion. The response to air-jet stimulation was also significantly enhanced at the highest dose of strychnine. These findings indicate that glycinergic neurons participate in the control of the flow of information conveyed to Sp5O nociceptive neurons by myelinated low-threshold mechanoreceptive afferents. Thus, alteration of trigeminal glycinergic modulation may contribute to the dynamic mechanical allodynia that occurs in trigeminal neuropathies.

Somatotopic distribution of trigeminal nociceptive neurons in ventrobasal complex of cat thalamus

1985 ◽  
Vol 53 (6) ◽  
pp. 1387-1400 ◽  
Author(s):  
T. Yokota ◽  
N. Koyama ◽  
N. Matsumoto
Keyword(s):  
Receptive Field ◽  
Dynamic Range ◽  
Tooth Pulp ◽  
Mechanical Stimuli ◽  
Canine Tooth ◽  
Light Pressure ◽  
Nociceptive Neurons ◽  
Low Threshold ◽  
Rostral Part ◽  
Shell Region

Recordings were made from single thalamic units in the urethan-chloralose anesthetized cat. Altogether 2,905 trigeminal single units having a receptive field in the contralateral trigeminal integument were isolated from the somatosensory part of nucleus ventralis posteromedialis, or VPM proper. Each isolated unit was tested for responses to a series of mechanical stimuli. The stimuli included brushing the skin, touch, pressure, noxious pinch, and pinpricks. The majority of VPM proper units responded with the greatest discharge frequency to gentle mechanical stimulation: either hair movement or light pressure to the trigeminal integument, but 341 units were identified as trigeminal nociceptive units. They were partitioned into two functionally defined subclasses, nociceptive specific (NS) and wide dynamic range (WDR) units, but not intermingled with low-threshold mechanoreceptive (LTM) units. Both NS and WDR units were found at or near the margin of the VPM proper but not outside this nucleus. This marginal area was referred to as the shell region of the VPM proper. A total of 248 NS units was found within the shell region of the caudal third of the VPM proper. This part was called the NS zone. These units were somatotopically organized. In the rostral part of the NS zone, ophthalmic NS units having a receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary NS units occurred dorsomedially, and mandibular NS units were found ventromedially. In the caudal part of the NS zone, maxillary NS units were encountered in the dorsal shell region, whereas mandibular NS units were found in the ventromedial shell region. Ophthalmic NS units were not found in this part of the NS zone. Altogether 93 WDR units were encountered in the shell region of the VPM proper. They were confined to a narrow band approximately 300 micron wide just rostral to the NS zone. These units were somatotopically organized. Ophthalmic WDR units having a low-threshold center of the receptive field in the contralateral ophthalmic division were located dorsolaterally, maxillary WDR units were located dorsomedially, and mandibular WDR units were located ventromedially. The majority of maxillary as well as mandibular WDR units were activated by electrical stimulation of the contralateral maxillary and/or mandibular canine tooth pulp afferents. Both NS and WDR zones of the VPM proper extended into the shell region of the nucleus ventralis posterolateralis (VPL).(ABSTRACT TRUNCATED AT 400 WORDS)

Response Properties of Dural Nociceptors in Relation to Headache

2006 ◽  
Vol 95 (3) ◽  
pp. 1298-1306 ◽  
Author(s):  
Andrew M. Strassman ◽  
Dan Levy
Keyword(s):  
Sensory Neurons ◽  
Neurotransmitter Release ◽  
Inhibitory Effect ◽  
Mixed Effects ◽  
Electrophysiological Recording ◽  
Mechanical Stimuli ◽  
Nociceptive Neurons ◽  
Calcium Dependent ◽  
General Studies

Single-unit electrophysiological recording studies have examined the activity of sensory neurons in the trigeminal ganglion that innervate the intracranial meninges to better understand their possible role in headache. A key question is whether the meningeal sensory neurons are similar to nociceptive neurons in other tissues or, alternatively, whether they have unique properties that might be of significance for headache pathogenesis and drug therapy. Such studies have indeed found that the intracranial dura is innervated by neurons that exhibit properties characteristic of nociceptors in other tissues, including chemosensitivity and sensitization. This sensitization, consisting of an enhanced responsiveness to mechanical stimuli, might be relevant to symptoms that are characteristic of certain headaches that indicate the presence of an exaggerated intracranial mechanosensitivity. Studies that examined whether the anti-migraine agent sumatriptan might inhibit this sensitization (in addition to its well-known inhibition of neurotransmitter release) found that it had no inhibitory effect but rather produced a calcium-dependent discharge, which might account for the initial worsening of headache that can follow sumatriptan administration. In studies that examined the effects of vasodilator agents, nitroprusside produced mixed effects on mechanosensitivity, whereas calciton gene-related peptide (CGRP) had no effect on either spontaneous or mechanically evoked discharge. These results call into question the role of vasodilation in headache and suggest that the role of CGRP in headache may be through its action as a central neurotransmitter rather than through vasodilation and activation of meningeal nociceptors. In general, studies of meningeal sensory neurons have not found evidence of unique properties that distinguish them from nociceptive neurons in other tissues. Ultimately the distinctive clinical characteristics of headache may prove to be related not so much to any differences in the intrinsic molecular or cellular properties of the meningeal sensory neurons but rather to the distinctive properties of the tissue that they innervate.

Spinal Strychnine Alters Response Properties of Nociceptive-Specific Neurons in Rat Medial Thalamus

1997 ◽  
Vol 78 (2) ◽  
pp. 628-637 ◽  
Author(s):  
Stephen E. Sherman ◽  
Lei Luo ◽  
Jonathan O. Dostrovsky
Keyword(s):  
Glycine Receptor ◽  
Afferent Input ◽  
Spinal Reflexes ◽  
Medial Thalamus ◽  
Nociceptive Neurons ◽  
Response Properties ◽  
Nociceptive Pathways ◽  
Air Jet ◽  
Tactile Stimuli ◽  
Tactile Input

Sherman, Stephen E., Lei Luo, and Jonathan O. Dostrovsky. Spinal strychnine alters response properties of nociceptive-specific neurons in rat medial thalamus. J. Neurophysiol. 78: 628–637, 1997. Experiments in both conscious and anesthetized animals indicate that intrathecal (i.t.) strychnine (STR; glycine receptor antagonist) produces acute, reversible allodynia, as evidenced by inappropriate behavioral and autonomic responses to cutaneous tactile stimuli. Although STR is known to produce disinhibition of afferent input to the spinal cord, changes in spinal reflexes cannot fully explain the complex behaviors observed following i.t. STR. Which supraspinal sites are involved in STR-dependent allodynia and how this abnormal somatosensory message is relayed to these sites remain to be determined. The medial thalamus contains many nociceptive-specific (NS) neurons and is believed to be involved in mediating the affective-motivational aspects of pain. It is thus important to determine whether spinally administered STR elicits changes in the responses of medial thalamic NS neurons. Extracellular single-unit recordings were conducted in urethan-anesthetized rats (290–490 g). A detailed characterization of 20 thalamic NS units (1 per rat; 2 in 1 case) was conducted before and immediately after i.t. STR (40 μg). Initially, all of the units in this study were classified as NS, because they were excited by noxious pinch but not by innocuous tactile stimuli. After i.t. STR, all (formerly NS) units exhibited significant responses to innocuous tactile stimuli (brush and/or air jet) applied to lumbar or sacral dermatomes. This effect of STR on thalamic NS neurons was acute and reversible. The majority of units (11 of 20) also exhibited an increase in spontaneous firing rate. Although the complete pinch receptive field (RF) could not be determined for all units, the available data indicate that the RFs for brush stimulation after i.t. STR were substantially different from the pre-STR pinch RFs for all but three units. The same i.t. STR injection that caused the observed changes in medial thalamus also produced allodynia, in the form of brush-evoked cardiovascular or motor responses, in 18 of the 19 rats. The ability of NS cells in medial thalamus to respond to tactile input after i.t. STR suggests that the STR lowers the threshold of nociceptive neurons that project directly and/or indirectly to medial thalamus. These observations suggest that ascending nociceptive pathways and medial thalamic structures contribute to the expression of STR-dependent allodynia.

Enhancement of Spontaneous and Heat-Evoked Activity in Spinal Nociceptive Neurons by the Endovanilloid/Endocannabinoid N-Arachidonoyldopamine (NADA)

2006 ◽  
Vol 95 (2) ◽  
pp. 1207-1212 ◽  
Author(s):  
Susan M. Huang ◽  
J. Michael Walker
Keyword(s):  
Thermal Hyperalgesia ◽  
Neural Correlates ◽  
Spontaneous Discharge ◽  
Nociceptive Neurons ◽  
Cb1 Antagonist ◽  
Trpv1 Antagonist ◽  
Evoked Activity ◽  
Dose Dependent ◽  
Thermal Stimuli

N-arachidonoyldopamine (NADA) is an endogenous molecule found in the nervous system that is capable of acting as a vanilloid agonist via the TRPV1 receptor and as a cannabinoid agonist via the CB1 receptor. Using anesthetized rats, we investigated the neural correlates of behavioral thermal hyperalgesia produced by NADA. Extracellular single cell electrophysiology was conducted to assess the effects of peripheral administration of NADA (i.pl.) on nociceptive neurons in the dorsal horn of the spinal cord. Injection of NADA in the hindpaw caused increased spontaneous discharge of spinal nociceptive neurons compared with injection of vehicle. The neurons also displayed magnified responses to application of thermal stimuli ranging from 34 to 52°C. NADA-induced neural hypersensitivity was dose dependent (EC50 = 1.55 μg) and TRPV1 dependent, as the effect was abolished by co-administration of the TRPV1 antagonist 5′-iodoresiniferatoxin (I-RTX). In contrast, co-administration of the CB1 antagonist SR 141716A did not attenuate this effect. These results suggest that the enhanced responses of spinal nociceptive neurons likely underlie the behavioral thermal hyperalgesia and implicate a possible pain-sensitizing role of endogenous NADA mediated by TRPV1 in the periphery.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

Investigation on the antibacterial activity of electronic cigarette liquids (ECLs): a proof of concept study

2020 ◽  
Vol 21 ◽  
Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Bacterial Species ◽  
A549 Cells ◽  
Bactericidal Effect ◽  
Minimal Bactericidal Concentration ◽  
Viability Assay ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

scholarly journals Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

2021 ◽  
Vol 22 (9) ◽  
pp. 4717
Author(s):  
Jin-Young Lee ◽  
Da-Ae Kim ◽  
Eun-Young Kim ◽  
Eun-Ju Chang ◽  
So-Jeong Park ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Map Kinases ◽  
Osteoclast Differentiation ◽  
Dependent Manner ◽  
Dual Action ◽  
Dose Dependent ◽  
Resorptive Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

scholarly journals A zebrafish model of infection-associated acute kidney injury

2018 ◽  
Vol 315 (2) ◽  
pp. F291-F299 ◽  
Author(s):  
Xiaoyan Wen ◽  
Liyan Cui ◽  
Seth Morrisroe ◽  
Donald Maberry ◽  
David Emlet ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Unmet Need ◽  
Kidney Injury ◽  
Edwardsiella Tarda ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Pericardial Edema ◽  
Kidney Injury Molecule 1 ◽  
Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

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