Differential blockade of cat dorsal root C fibers by various chloride solutions

1972 ◽  
Vol 36 (5) ◽  
pp. 569-583 ◽  
Author(s):  
J. Stovall King ◽  
Don L. Jewett ◽  
Howard R. Sundberg
Keyword(s):  
Hypertonic Saline ◽  
Choline Chloride ◽  
Isotonic Saline ◽  
Chloride Ion ◽  
Content Type ◽  
Persistent Effect ◽  
C Fibers ◽  
C Fiber ◽  
Intrathecal Infusion

✓ A possible mechanism by which intrathecal infusion of partially frozen saline might relieve patients of chronic pain has been studied by applying hypertonic saline to the dorsal rootlets of cats in vitro. The supernatant of partially thawed normal saline was found to be hypertonic. Persistent block of C fibers, detected by a collision method, occurred after the rootlets had been exposed to saline from 500 to 2500 mOsm/L for 15 min followed by 15 min of isotonic saline. Few of the A fibers were blocked by this procedure, but both A and C fibers were blocked when solutions of 3500 mOsm/L were used. Differential blockage of C fibers could also be produced with hypotonic saline and with distilled water. Localized cooling, to 2°C for 25 min, had no persistent effect on C fiber conduction, and when cooling was combined with hypertonic saline there was no potentiation of the differential blockade caused by the saline. Hypertonic solutions of sucrose or sodium nitrate produced no persistent differential block; most A and C fibers recovered. However, choline chloride was as effective as sodium chloride in giving a differential blockade. It seems that chloride ion plays a major role in establishing the persistent C fiber blockade observed when dorsal rootlets are exposed to hypertonic saline.

B2 Receptor–Mediated Enhanced Bradykinin Sensitivity of Rat Cutaneous C-Fiber Nociceptors During Persistent Inflammation

2001 ◽  
Vol 86 (6) ◽  
pp. 2727-2735 ◽  
Author(s):  
Ratan Kumar Banik ◽  
Yasuko Kozaki ◽  
Jun Sato ◽  
Lajos Gera ◽  
Kazue Mizumura
Keyword(s):  
Receptor Subtype ◽  
Response Curves ◽  
C Fibers ◽  
B1 Receptor ◽  
Persistent Inflammation ◽  
C Fiber ◽  
Inflammatory State ◽  
Tissue Sensitivity ◽  
Sensitizing Effect

Bradykinin (BK), which has potent algesic and sensitizing effect on nociceptors, is of current interest in understanding the mechanisms of chronic pain. BK response is mediated by B2 receptor in normal conditions; however, findings that B1 receptor blockade alleviated hyperalgesia in inflammation have been highlighting the role of B1 receptor in pathological conditions. It has not yet been clear whether nociceptor activities are modified by B1 receptor agonists or antagonists during inflammation. In addition, previous studies reported the change in BK sensitivity of nociceptors during short-lasting inflammation, and data in persistent inflammation are lacking. Therefore we investigated whether an experimentally induced persistent inflammatory state modulates the BK sensitivity of nociceptors and which receptor subtype plays a more important role in this condition. Complete Freund's adjuvant was injected into the rat-tail and after 2–3 wk, persistent inflammation developed, which was prominent in the ankle joint. Using an in vitro skin-saphenous nerve preparation, single-fiber recordings were made from mechano-heat sensitive C-fiber nociceptors innervating rat hairy hindpaw skin, and their responses were compared with those obtained from C-fibers tested similarly in normal animals. BK at 10−8 M excited none of the 10 C-fibers in normal animals while it excited 5 of 11 (45%) C-fibers of inflamed animals, and at 10−6 M BK excited all of the 11 inflamed C-fibers (or 94% of 36 tested C-fibers) but only 4 of 10 (or 45% of 58 tested C-fibers) in normal animals. Thus the concentration-response curves based on the incidence of BK induced excitation, and the total number of impulses evoked in response to BK were significantly shifted to the left. Moreover, an increased percentage of the inflamed C-fibers responded to 10−6 M BK with bursting or high-frequency discharges. Thirty-percent of inflamed C-fibers had spontaneous activity, and these fibers showed comparatively less tachyphylaxis to consecutive second and third 10−6 M BK stimulation. A B2 receptor antagonist (d-Arg-[Hyp3, Thi5,8,d-phe7]-BK) completely eliminated BK responses in inflamed rats, while B1 receptor antagonists (B 9958 and Des-Arg9-[Leu8]-BK) had no effect. Selective B1 receptor agonist (Des-Arg10-Kallidin) excited 46% ( n = 13) of inflamed C-fibers at 10−5 M concentration, which is 1,000 times higher than that of BK needed to excite the same percentage of inflamed C-fibers. We conclude that in chronically inflamed tissue, sensitivity of C-fiber nociceptors to BK, which is B2 receptor mediated, is strongly increased and that B1 receptor may not be important to a persistent inflammatory state, at least at the primary afferent level.

Serotonin increases excitability of rabbit C-fiber neurons by two distinct mechanisms

1989 ◽  
Vol 67 (2) ◽  
pp. 584-591 ◽  
Author(s):  
E. P. Christian ◽  
G. E. Taylor ◽  
D. Weinreich
Keyword(s):  
Impulse Activity ◽  
Repetitive Firing ◽  
Receptor Subtype ◽  
Potential Contribution ◽  
Action Potential Firing ◽  
C Fibers ◽  
C Fiber ◽  
Ganglion Neurons

Serotonin (5-HT) increases impulse activity in visceral afferent C-fibers in vivo. A 5-HT-induced membrane depolarization may partially account for this effect. Here, we examined the potential contribution of an additional mechanism to the 5-HT-mediated increase in impulse activity. Approximately 40% of rabbit visceral C-fiber neurons exhibit a protracted (greater than 3 s) spike afterhyperpolarization (AHPslow) that is a major determinant of repetitive firing properties in these neurons. Intracellular recording methods were applied to rabbit nodose ganglion neurons in vitro to assess whether 5-HT could increase excitability through effects on the AHPslow. Results revealed a concentration-dependent 5-HT-mediated depression of the AHPslow amplitude and duration that was accompanied by decreased accommodation of action potential firing. Experiments with 5-HT receptor antagonists further showed that this autacoid depressed the AHPslow through a different 5-HT receptor subtype than that subserving the 5-HT-induced depolarization. Thus the AHPslow represents a distinct locus where 5-HT can increase the impulse activity of these visceral C-fiber afferents.

Peripheral nerve stimulation suppression of C-fiber-evoked flexion reflex in rats

1988 ◽  
Vol 68 (2) ◽  
pp. 279-283 ◽  
Author(s):  
Bengt H. Sjölund
Keyword(s):  
Nerve Stimulation ◽  
Repetition Rate ◽  
Systematic Investigation ◽  
Content Type ◽  
Flexion Reflex ◽  
C Fibers ◽  
Group I ◽  
C Fiber ◽  
Evoked Activity ◽  
Stimulation Of

✓ Transcutaneous electrical nerve stimulation (TENS) is an acknowledged clinical technique to alleviate chronic pain. Its effectiveness is still limited, however, and the stimulation parameters used are based on subjective reports from patients. In the present study, the systematic investigation of conditioning stimulation that was previously reported by the author has been extended to include short trains of stimuli at a low repetition rate (0.1 to 5 Hz) delivered to dissected skin and muscle nerves in the lightly anesthetized rat. The size of a C-fiber-evoked flexion reflex was utilized as a measure of transmission from nociceptive afferentnerve fibers in the spinal cord and was tested repeatedly after 30 minutes of conditioning TENS-like stimulation to adjacent nerves. At these low rates, stimulation of a muscle nerve was usually more effective in suppressing transmission from C-fibers to second-order neurons than was stimulation of a skin nerve. Furthermore, a stimulation strength recruiting both Group I–II and III muscle afferent fibers was more effective in depressing the C-fiber-evoked activity at all frequencies studied than was that activating Group I–II fibers only. A pulsetrain repetition rate of around 1 Hz was most effective. These findings should be taken into account when carrying out clinical TENS treatment.

Characterization of Neuronal Nicotinic Acetylcholine Receptors in the Membrane of Unmyelinated Human C-Fiber Axons by In Vitro Studies

2003 ◽  
Vol 90 (5) ◽  
pp. 3295-3303 ◽  
Author(s):  
P. M. Lang ◽  
R. Burgstahler ◽  
W. Sippel ◽  
D. Irnich ◽  
B. Schlotter-Weigel ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Rank Order ◽  
Axonal Membrane ◽  
Nicotinic Acetylcholine ◽  
C Fibers ◽  
C Fiber ◽  
Intracellular Ca ◽  
Axonal Excitability

Application of acetylcholine to peripheral nerve terminals in the skin is a widely used test in studies of human small-fiber functions. However, a detailed pharmacological profile and the subunit composition of nicotinic acetylcholine receptors in human C-fiber axons are not known. In the present study, we recorded acetylcholine-induced changes of the excitability and of the intracellular Ca2+ concentration in C-fiber axons of isolated human nerve segments. In addition, using immunohistochemistry, an antibody of a subtype of nicotinic acetylcholine receptor was tested. Acetylcholine and agonists reduced the current necessary for the generation of action potentials in C fibers by ≤30%. This increase in axonal excitability was accompanied by a rise in the free intracellular Ca2+ concentration. The following rank order of potency for agonists was found: epibatidine >> 5-Iodo-A-85380 > 1,1-dimethyl-4-phenylpiperazinium iodide > nicotine > cytisine > acetylcholine; choline had no effect. The epibatidine-induced increase in axonal excitability was blocked by mecamylamine and, less efficiently, by methyllycacontine and dihydro-β-erythroidine. Many C-fiber axons were labeled by an antibody that recognizes the α5 subunit of nicotinic acetylcholine receptors. In summary, electrophysiological and immunohistochemical data indicate the functional expression of nicotinic acetylcholine receptors composed of α3, α5, and β4 but not of α4/β2 or of α7 subunits in the axonal membrane of unmyelinated human C fibers. In addition, the observations suggest that the axonal membrane of C fibers in isolated segments of human sural nerve can be used as a model for presumed cholinergic chemosensitivity of axonal terminals.

scholarly journals Targeting Multidrug-Resistant Acinetobacter spp.: Sulbactam and the Diazabicyclooctenone β-Lactamase Inhibitor ETX2514 as a Novel Therapeutic Agent

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Melissa D. Barnes ◽  
Vijay Kumar ◽  
Christopher R. Bethel ◽  
Samir H. Moussa ◽  
John O’Donnell ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Chloride Ion ◽  
Multidrug Resistant ◽  
Infection Model ◽  
Content Type ◽  
Class A ◽  
Hydrogen Bonding Interactions ◽  
Class D ◽  
Acinetobacter Spp

ABSTRACT Multidrug-resistant (MDR) Acinetobacter spp. poses a significant therapeutic challenge in part due to the presence of chromosomally encoded β-lactamases, including class C Acinetobacter-derived cephalosporinases (ADC) and class D oxacillinases (OXA), as well as plasmid-mediated class A β-lactamases. Importantly, OXA-like β-lactamases represent a gap in the spectrum of inhibition by recently approved β-lactamase inhibitors such as avibactam and vaborbactam. ETX2514 is a novel, rationally designed, diazabicyclooctenone inhibitor that effectively targets class A, C, and D β-lactamases. We show that addition of ETX2514 significantly increased the susceptibility of clinical Acinetobacter baumannii isolates to sulbactam. AdeB and AdeJ were identified to be key efflux constituents for ETX2514 in A. baumannii. The combination of sulbactam and ETX2514 was efficacious against A. baumannii carrying blaTEM-1, blaADC-82, blaOXA-23, and blaOXA-66 in a neutropenic murine thigh infection model. We also show that, in vitro, ETX2514 inhibited ADC-7 (k2/Ki 1.0 ± 0.1 × 106 M−1 s−1) and OXA-58 (k2/Ki 2.5 ± 0.3 × 105 M−1 s−1). Cocrystallization of ETX2514 with OXA-24/40 revealed hydrogen bonding interactions between ETX2514 and residues R261, S219, and S128 of OXA-24/40 in addition to a chloride ion occupied in the active site. Further, the C3 methyl group of ETX2514 shifts the position of M223. In conclusion, the sulbactam-ETX2514 combination possesses a broadened inhibitory range to include class D β-lactamases as well as class A and C β-lactamases and is a promising therapeutic candidate for infections caused by MDR Acinetobacter spp. IMPORTANCE The number and diversity of β-lactamases are steadily increasing. The emergence of β-lactamases that hydrolyze carbapenems poses a significant threat to our antibiotic armamentarium. The explosion of OXA enzymes that are carbapenem hydrolyzers is a major challenge (carbapenem-hydrolyzing class D [CHD]). An urgent need exists to discover β-lactamase inhibitors with class D activity. The sulbactam-ETX2514 combination demonstrates the potential to become a treatment regimen of choice for Acinetobacter spp. producing class D β-lactamases.

scholarly journals Responses of cutaneous C-fiber afferents and spinal microglia after hindlimb cast immobilization in rats

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hiroki Ota ◽  
Haruna Takebe ◽  
Kazue Mizumura ◽  
Toru Taguchi
Keyword(s):  
Mechanical Response ◽  
Response Threshold ◽  
Lumbar Spinal Cord ◽  
Cast Immobilization ◽  
C Fibers ◽  
Electrophysiological Recordings ◽  
C Fiber ◽  
Lumbar Spinal ◽  
Limb Immobilization

AbstractPrevious studies have shown that persistent limb immobilization using a cast increases nociceptive behavior to somatic stimuli in rats. However, the peripheral neural mechanisms of nociception remain unclear. Using single-fiber electrophysiological recordings in vitro, we examined the general characteristics of cutaneous C-fiber afferents in the saphenous nerve and their responsiveness to mechanical and heat stimuli in a rat model of immobilization-induced pain by subjecting the rats to hindlimb cast immobilization for 4 weeks. The mechanical response of C-fibers appeared to increase in the model; however, statistical analysis revealed that neither the response threshold nor the response magnitude was altered. The general characteristics and heat responses of the C-fibers were not altered. The number of microglia and cell diameters significantly increased in the superficial dorsal horn of the lumbar spinal cord. Thus, activated microglia-mediated spinal mechanisms are associated with the induction of nociceptive hypersensitivity in rats after persistent cast immobilization.

The dependence of human decidual prolactin production and secretion on the osmotic environment in vitro

1984 ◽  
Vol 106 (3) ◽  
pp. 405-410 ◽  
Author(s):  
Jesper Rye Andersen ◽  
Birgit Borggaard ◽  
Erik Schroeder ◽  
Elith Bjarne Olsen ◽  
Hans Stimpel ◽  
...  
Keyword(s):  
Sodium Chloride ◽  
Potassium Chloride ◽  
Production Rate ◽  
Choline Chloride ◽  
Chloride Ion ◽  
Decidual Tissue ◽  
The Mean ◽  
Decidual Prolactin

Abstract. Human decidual tissue from uncomplicated term pregnancies was incubated in vitro using a cross-over design of incubation lasting for 72 h. The decidual tissue of each membrane was added sequentially to media with the osmolalities 252, 315 and 387 mmol/kg, and the different osmolalities were in 33 experiments induced by changing the concentration either of sodium chloride, potassium chloride, mannitol, sucrose, or choline chloride. At 387 mmol/kg all substances elicited a significant increase in Prl secretion compared with the 315 mmol/kg media (14–27%) or the 252 mmol/kg media (26–46%). When the sodium chloride, potassium chloride, sucrose, and choline chloride media at 387 mmol/kg were compared in another 7 experiments, potassium chloride increased Prl secretion more effectively than the others (10%, P < 0.05). The incubation cross-over design did not permit determination of the decidual Prl content after incubation in each of the various media, but in 28 experiments the mean decidual Prl content was 12.7 mIU per 100 mg dry tissue (range 4–30) before and 8.7 mIU per 100 mg dry tissue (1–17) after the experiments. The mean amount of Prl secreted during the successive incubations was 152.2 mIU per 100 mg dry tissue (19–672) which showed the secretion to be a result of continued Prl production. The effect of osmolality was independent of the basal production rate. These results indicate that the intracellular ionic concentrations, probably of potassium ion or of chloride ion, are of importance in the regulation of the synthesis and secretion of decidual Prl in vitro.

Inhibition of primate spinothalamic tract cells by TENS

1985 ◽  
Vol 62 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Kyu Ho Lee ◽  
Jin Mo Chung ◽  
William D. Willis
Keyword(s):  
Receptive Field ◽  
Common Peroneal Nerve ◽  
High Rate ◽  
Evoked Responses ◽  
Endogenous Opioid ◽  
Spinothalamic Tract ◽  
Content Type ◽  
C Fibers ◽  
C Fiber ◽  
Fine Print

✓ Transcutaneous electrical nerve stimulation (TENS) was applied in an experimental animal model to investigate the underlying mechanisms of this treatment. Recordings were made from identified spinothalamic tract (STT) neurons in the lumbosacral spinal cords of seven anesthetized monkeys. The STT cells were activated by stimulating the common peroneal nerve at a suprathreshold intensity for C-fibers. Evoked responses of C-fibers were compared before, during, and after application of TENS for 5 minutes from a commercially available TENS unit. The current delivered by the TENS unit was monitored. In 14 STT cells, some degree of inhibition of C-fiber evoked responses occurred only when the intensity of TENS exceeded the threshold of Aδ fibers. At a given stimulus intensity, bursts of pulses repeated at a low rate were more effective than high-rate pulses. When TENS was applied to an area of the skin within a cell's receptive field, it was more effective than when it was applied outside the receptive field. The C-fiber volley recorded from a peripheral nerve was not reduced in size, and there were no substantial changes in its latency due to TENS. The inhibition of the activity of STT cells was not altered appreciably after intravenous injection of naloxone hydrochloride. These results suggest that TENS produces central nervous system inhibition by activating Aδ afferent fibers. The inhibitory effects of TENS on STT cells appear to be due to a mechanism that does not involve release of endogenous opioid substances.

scholarly journals 2-Aminoethoxydiphenyl borate stimulates pulmonary C neurons via the activation of TRPV channels

2005 ◽  
Vol 288 (5) ◽  
pp. L932-L941 ◽  
Author(s):  
Qihai Gu ◽  
Ruei-Lung Lin ◽  
Hong-Zhen Hu ◽  
Michael X. Zhu ◽  
Lu-Yuan Lee
Keyword(s):  
Transient Receptor Potential ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
C Fibers ◽  
Trpv Channels ◽  
C Fiber ◽  
Aminoethoxydiphenyl Borate

This study was carried out to determine the effect of 2-aminoethoxydiphenyl borate (2-APB), a common activator of transient receptor potential vanilloid (TRPV) type 1, 2, and 3 channels, on cardiorespiratory reflexes, pulmonary C fiber afferents, and isolated pulmonary capsaicin-sensitive neurons. In anesthetized, spontaneously breathing rats, intravenous bolus injection of 2-APB elicited the pulmonary chemoreflex responses, characterized by apnea, bradycardia, and hypotension. After perineural treatment of both cervical vagi with capsaicin to block the conduction of C fibers, 2-APB no longer evoked any of these reflex responses. In open-chest and artificially ventilated rats, 2-APB evoked an abrupt and intense discharge in vagal pulmonary C fibers in a dose-dependent manner. The stimulation of C fibers by 2-APB was attenuated but not abolished by capsazepine, a selective antagonist of the TRPV1, which completely blocked the response to capsaicin in these C fiber afferents. In isolated pulmonary capsaicin-sensitive neurons, 2-APB concentration dependently evoked an inward current that was partially inhibited by capsazepine but almost completely abolished by ruthenium red, an effective blocker of all TRPV channels. In conclusion, 2-APB evokes a consistent and distinct stimulatory effect on pulmonary C fibers in vivo and on isolated pulmonary capsaicin-sensitive neurons in vitro. These results establish the functional evidence demonstrating that TRPV1, V2, and V3 channels are expressed on these sensory neurons and their terminals.

Physiological and hypertonic saline solutions impair ciliary activity in vitro

2000 ◽  
Vol 25 (4) ◽  
pp. 331-332
Author(s):  
W.M. Boek ◽  
N. Keles ◽  
K. Graamans ◽  
E.H. Huizing
Keyword(s):  
Hypertonic Saline ◽  
Ciliary Activity ◽  
Saline Solutions
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