Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways

2002 ◽  
Vol 282 (4) ◽  
pp. L775-L781 ◽  
Author(s):  
Allen C. Myers ◽  
Radhika Kajekar ◽  
Bradley J. Undem
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Sensory Neurons ◽  
Large Diameter ◽  
Sensory System ◽  
Small Diameter ◽  
Allergic Inflammation ◽  
Primary Afferent ◽  
Chemical Coding ◽  
Low Threshold

In the vagal-sensory system, neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) are synthesized nearly exclusively in small-diameter nociceptive type C-fiber neurons. By definition, these neurons are designed to respond to noxious or tissue-damaging stimuli. A common feature of visceral inflammation is the elevation in production of sensory neuropeptides. Little is known, however, about the physiological characteristics of vagal sensory neurons induced by inflammation to produce substance P. In the present study, we show that allergic inflammation of guinea pig airways leads to the induction of substance P and CGRP production in large-diameter vagal sensory neurons. Electrophysiological and anatomical evidence reveals that the peripheral terminals of these neurons are low-threshold Aδ mechanosensors that are insensitive to nociceptive stimuli such as capsaicin and bradykinin. Thus inflammation causes a qualitative change in chemical coding of vagal primary afferent neurons. The results support the hypothesis that during an inflammatory reaction, sensory neuropeptide release from primary afferent nerve endings in the periphery and central nervous system does not require noxious or nociceptive stimuli but may also occur simply as a result of stimulation of low-threshold mechanosensors. This may contribute to the heightened reflex physiology and pain that often accompany inflammatory diseases.

Tachykinins mediate slow excitatory postsynaptic transmission in guinea pig sphincter of Oddi ganglia

2001 ◽  
Vol 281 (2) ◽  
pp. G357-G364 ◽  
Author(s):  
Brian P. Manning ◽  
Gary M. Mawe
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Synaptic Input ◽  
Intracellular Recording ◽  
Small Diameter ◽  
Sphincter Of Oddi ◽  
Receptor Desensitization ◽  
Afferent Fibers ◽  
Excitatory Synaptic Input

Intracellular recording techniques were used to test whether tachykinins could be mediators of slow excitatory postsynaptic potentials (EPSPs) in guinea pig sphincter of Oddi (SO) ganglia. Application of the tachykinin substance P (SP) onto SO neurons caused a prolonged membrane depolarization that was reminiscent of the slow EPSP in these cells. Pressure ejection of the neurokinin 3 (NK3) receptor-specific agonist senktide caused a similar depolarization; however, no responses were detected on application of NK1 or NK2 receptor agonists. The NK3 receptor antagonist SR-142801 (100 nM) significantly inhibited both SP-induced depolarization and the stimulation-evoked slow EPSP, as did NK3 receptor desensitization with senktide. Capsaicin, which causes the release of SP from small-diameter afferent fibers, induced a depolarization that was similar to the evoked slow EPSP in both amplitude and duration. The capsaicin-induced depolarization was significantly attenuated in the presence of SR-142801. These data indicate that tachykinins, released from extrinsic afferent fibers, act via NK3 receptors to provide slow excitatory synaptic input to SO neurons.

Characterization of six voltage-gated K+ currents in adult rat sensory neurons

1996 ◽  
Vol 75 (6) ◽  
pp. 2629-2646 ◽  
Author(s):  
M. S. Gold ◽  
M. J. Shuster ◽  
J. D. Levine
Keyword(s):  
Action Potential ◽  
Sensory Neurons ◽  
Large Diameter ◽  
Small Diameter ◽  
Pharmacological Properties ◽  
Drg Neurons ◽  
Voltage Gated ◽  
Adult Rat ◽  
Whole Cell Patch Clamp ◽  
K Currents

1. Previously three voltage-gated K+ currents were described in neurons from mammalian sensory ganglia: two transient and one sustained. Because there is considerable variability in the gating properties of these three currents, we have investigated the possibility that this variability reflects the presence of additional currents in sensory neurons. 2. Using whole cell patch-clamp techniques, we provide evidence for the existence of six voltage-gated K+ currents in cultured dorsal root ganglion (DRG) neurons from the adult rat. The six currents were identified on the basis of distinct biophysical and pharmacological properties; three currents are transient (IAf, IAht, and IAs), and three are sustained (IKi, IKlt, and IKn). 3. In addition to possessing distinct biophysical and pharmacological properties, four of the six currents are differentially expressed among subpopulations of DRG neurons. IAht is selectively expressed in small-diameter neurons. IKi is expressed more frequently in neurons with an action-potential shoulder, and both IAht and IAs are selectively coexpressed in neurons that respond to the algogenic agent capsaicin. IAf is selectively expressed in large-diameter neurons and is the only current expressed more frequently in neurons without an action-potential shoulder. 4. It is likely that much of apparent variability in the properties of the three voltage-gated K+ currents reported previously in vertebrate sensory neurons can be accounted for by the existence of at least three additional voltage-gated K+ currents described in this report.

Allergen-induced substance P synthesis in large-diameter sensory neurons innervating the lungs

2005 ◽  
Vol 116 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Benjamas Chuaychoo ◽  
Dawn D. Hunter ◽  
Allen C. Myers ◽  
Marian Kollarik ◽  
Bradley J. Undem
Keyword(s):  
Substance P ◽  
Sensory Neurons ◽  
Large Diameter

scholarly journals Expression of sphingosine 1-phosphate receptors in the rat dorsal root ganglia and defined single isolated sensory neurons

2012 ◽  
Vol 44 (18) ◽  
pp. 889-901 ◽  
Author(s):  
J. S. Kays ◽  
Chao Li ◽  
G. D. Nicol
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Excitability ◽  
Expression Profiles ◽  
Large Diameter ◽  
Small Diameter ◽  
Positive Control ◽  
Single Neurons ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Previously, we demonstrated that sphingosine 1-phosphate (S1P) increased the excitability of small-diameter sensory neurons, in part, through activation of S1P receptor 1 (S1PR1), suggesting that other S1PRs can modulate neuronal excitability. Therefore, studies were undertaken to establish the expression profiles of S1PRs in the intact dorsal root ganglion (DRG) and in defined single isolated sensory neurons. To determine mRNA expression of S1PRs in the DRG, SYBR green quantitative PCR (qPCR) was used. To determine the expression of S1PR mRNAs in single neurons of defined diameters, a preamplification protocol utilizing Taqman primer and probes was used to enhance the sensitivity of detection. The preamplification protocol also permitted detection of mRNA for two hallmark neuronal receptor/ion channels, TRPV1 and P2X3. Expression profiles of S1PR mRNA isolated from lung and brain were used as positive control tissues. In the intact DRG, the order of expression of S1PRs was S1PR3>>R1≈R2>R5≈R4. In the single neurons, the expression of S1PRs was quite variable with some neurons expressing all five subtypes, whereas some expressing only one subtype. In contrast to the DRG, S1PR1 was the highest expressing subtype in 10 of the 18 small-, medium-, and large-diameter sensory neurons. S1PR1 was the second highest expressor in ∼50% of those remaining neurons. Overall, in the single neurons, the order of expression was S1PR1>>R3≈R5>R4>R2. The results obtained from the single defined neurons are consistent with our previous findings wherein S1PR1 plays a prominent but not exclusive role in the enhancement of neuronal excitability.

Long-term IL-1β exposure causes subpopulation-dependent alterations in rat dorsal root ganglion neuron excitability

2012 ◽  
Vol 107 (6) ◽  
pp. 1586-1597 ◽  
Author(s):  
Patrick L. Stemkowski ◽  
Peter A. Smith
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Large Diameter ◽  
Small Diameter ◽  
Defined Medium ◽  
Drg Neurons ◽  
Enriched Cultures

The effect of interleukin-1β (IL-1β) on the electrical properties of sensory neurons was assessed at levels and exposure times comparable to those found in animal models of neuropathic pain. Experiments involved whole cell current-clamp recordings from rat dorsal root ganglion (DRG) neurons in defined-medium, neuron-enriched cultures. Five- to six-day exposure to 100 pM IL-1β produced subpopulation-dependent effects on DRG neurons. These included an increase in the excitability of medium-diameter and small-diameter isolectin B4 (IB4)-positive neurons that was comparable to that found after peripheral nerve injury. By contrast, a reduction in excitability was observed in large-diameter neurons, while no effect was found in small-diameter IB4-negative neurons. Further characterization of changes in medium and small IB4-positive neurons revealed that some, but not all, effects of IL-1β were mediated through its receptor, IL-1RI. Although the acute actions of IL-1β on sensory neurons have been well studied and related to acute and/or inflammatory pain, the present study shows how sensory neurons respond to long-term cytokine exposure. Such effects are relevant to understanding processes that contribute to the onset of neuropathic pain.

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