Activation of C Fibers by Metabolic Perturbations Associated with Tourniquet Ischemia

The lungs and esophagus are innervated by sensory neurons with somata in the nodose, jugular, and dorsal root ganglion. These sensory ganglia are derived from embryonic placode (nodose) and neural crest tissues (jugular and dorsal root ganglia; DRG). We addressed the hypothesis that the neuron's embryonic origin (e.g., placode vs. neural crest) plays a greater role in determining particular aspects of its phenotype than the environment in which it innervates (e.g., lungs vs. esophagus). This hypothesis was tested using a combination of extracellular and patch-clamp electrophysiology and single-cell RT-PCR from guinea pig neurons. Nodose, but not jugular C-fibers innervating the lungs and esophagus, responded to α,β-methylene ATP with action potential discharge that was sensitive to the P2X3 (P2X2/3) selective receptor antagonist A-317491. The somata of lung- and esophagus-specific sensory fibers were identified using retrograde tracing with a fluorescent dye. Esophageal- and lung-traced neurons from placodal tissue (nodose neurons) responded similarly to α,β-methylene ATP (30 μM) with a large sustained inward current, whereas in neurons derived from neural crest tissue (jugular and DRG neurons), the same dose of α,β-methylene ATP resulted in only a transient rapidly inactivating current or no detectable current. It has been shown previously that only activation of P2X2/3 heteromeric receptors produce sustained currents, whereas homomeric P2X3 receptor activation produces a rapidly inactivating current. Consistent with this, single-cell RT-PCR analysis revealed that the nodose ganglion neurons innervating the lungs and esophagus expressed mRNA for P2X2 and P2X3 subunits, whereas the vast majority of jugular and dorsal root ganglia innervating these tissues expressed only P2X3 mRNA with little to no P2X2 mRNA expression. We conclude that the responsiveness of C-fibers innervating the lungs and esophagus to ATP and other purinergic agonists is determined more by their embryonic origin than by the environment of the tissue they ultimately innervate.

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Nociceptive Sensitization by Activation of Protease-Activated Receptor 2 in a Rat Model of Incisional Pain

Brain Sciences ◽

10.3390/brainsci11020144 ◽

2021 ◽

Vol 11 (2) ◽

pp. 144

Author(s):

Kanta Kido ◽

Norika Katagiri ◽

Hiromasa Kawana ◽

Shigekazu Sugino ◽

Masanori Yamauchi ◽

...

Keyword(s):

Postoperative Pain ◽

Inflammatory Responses ◽

Early Period ◽

Intraplantar Injection ◽

C Fibers ◽

Nociceptive Responses ◽

Incisional Pain ◽

Protease Activated Receptor 2

Postoperative pain and consequent inflammatory responses after tissue incision adversely affects many surgical patients due to complicated mechanisms. In this study, we examined whether activation of protease-activated receptor 2 (PAR-2), which is stimulated by tryptase from mast cells, elicits nociception and whether the PAR-2 antagonist could reduce incisional nociceptive responses in vivo and in vitro. The effects of a selective PAR-2 antagonist, N3-methylbutyryl-N-6-aminohexanoyl-piperazine (ENMD-1068), pretreatment on pain behaviors were assessed after plantar incision in rats. The effects of a PAR-2 agonist, SLIGRL-NH2, on nociception was assessed after the injection into the hind paw. Furthermore, the responses of C-mechanosensitive nociceptors to the PAR-2 agonist were observed using an in vitro skin–nerve preparation as well. Intraplantar injection of SLIGRL-NH2 elicited spontaneous nociceptive behavior and hyperalgesia. Local administration of ENMD-1068 suppressed guarding behaviors, mechanical and heat hyperalgesia only within the first few hours after incision. SLIGRL-NH2 caused ongoing activity in 47% of C-mechanonociceptors in vitro. This study suggests that PAR-2 may support early nociception after incision by direct or indirect sensitization of C-fibers in rats. Moreover, PAR-2 may play a regulatory role in the early period of postoperative pain together with other co-factors to that contribute to postoperative pain.

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Pressure-clamped single-fiber recording technique: A new recording method for studying sensory receptors

Molecular Pain ◽

10.1177/1744806920927852 ◽

2020 ◽

Vol 16 ◽

pp. 174480692092785 ◽

Cited By ~ 1

Author(s):

Mayumi Sonekatsu ◽

Hiroshi Yamada ◽

Jianguo G Gu

Keyword(s):

Nerve Fiber ◽

Single Unit ◽

Single Fiber ◽

Single Unit Recording ◽

Sensory Receptors ◽

Unit Recording ◽

Recording Technique ◽

C Fibers ◽

Recording Method ◽

Single Nerve

An electrophysiological technique that can record nerve impulses from a single nerve fiber is indispensable for studying modality-specific sensory receptors such as low threshold mechanoreceptors, thermal receptors, and nociceptors. The teased-fiber single-unit recording technique has long been used to resolve impulses that are likely to be from a single nerve fiber. The teased-fiber single-unit recording technique involves tedious nerve separation procedures, causes nerve fiber impairment, and is not a true single-fiber recording method. In the present study, we describe a new and true single-fiber recording technique, the pressure-clamped single-fiber recording method. We have applied this recording technique to mouse whisker hair follicle preparations with attached whisker afferents as well as to skin-nerve preparations made from mouse hindpaw skin and saphenous nerves. This new approach can record impulses from rapidly adapting mechanoreceptors (RA), slowly adapting type 1 mechanoreceptors (SA1), and slowly adapting type 2 mechanoreceptors (SA2) in these tissue preparations. We have also applied the pressure-clamped single-fiber recordings to record impulses on Aβ-fibers, Aδ-fibers, and C-fibers. The pressure-clamped single-fiber recording technique provides a new tool for sensory physiology and pain research.

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Purine metabolite washout and platelet aggregation at reflow after tourniquet ischemia: effect of intravenous regional lidocaine

Acta Anaesthesiologica Scandinavica ◽

10.1111/j.1399-6576.1995.tb04228.x ◽

1995 ◽

Vol 39 (8) ◽

pp. 1053-1058 ◽

Cited By ~ 8

Author(s):

O. NAESH ◽

H. HALJAMAE ◽

M. SKIELBOE ◽

P. ANDERSEN ◽

F. SZTUK ◽

...

Keyword(s):

Platelet Aggregation ◽

Purine Metabolite ◽

Tourniquet Ischemia

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Neurophysiological basis for neurogenic-mediated articular cartilage anabolism alteration

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.280.1.r115 ◽

2001 ◽

Vol 280 (1) ◽

pp. R115-R122 ◽

Cited By ~ 7

Author(s):

Elvire Gouze-Decaris ◽

Lionel Philippe ◽

Alain Minn ◽

Philippe Haouzi ◽

Pierre Gillet ◽

...

Keyword(s):

Articular Cartilage ◽

Ex Vivo ◽

Cartilage Damage ◽

Intrathecal Injection ◽

Chronic Administration ◽

C Fibers ◽

Glutamatergic Synaptic Transmission ◽

C Fiber ◽

Fiber Stimulation ◽

Neurophysiological Basis

This study was designed to investigate the pathways involved in neurogenic-mediated articular cartilage damage triggered by a nonsystemic distant subcutaneous or intra-articular inflammation. The cartilage damage was assessed 24 h after subcutaneous or intra-articular complete Freund's adjuvant (CFA) injection measuring patellar proteoglycan (PG) synthesis (ex vivo [Na2 35SO4] incorporation) in 96 Wistar rats. Unilateral subcutaneous or intra-articular injection of CFA induced significant decrease (25–29%) in PG synthesis in both patellae. Chronic administration of capsaicin (50 mg · kg−1 · day−1 during 4 days), which blunted the normal response of C fiber stimulation, prevented the bilateral significant decrease in cartilage synthesis. Similarly, intrathecal injection of MK-801 (10 nmol/day during 5 days), which blocked the glutamatergic synaptic transmission at the dorsal horn of signal originating in primary afferent C fibers, eliminated the CFA-induced PG synthesis decrease in both patellae. Chemical sympathectomy, induced by guanethidine (12.5 mg · kg−1 · day−1 during 6 wk), also prevented PG synthesis alteration. Finally, compression of the spinal cord at the T3-T5 level had a similar protective effect on the reduction of [Na2 35SO4] incorporation. It is concluded that the signal that triggers articular cartilage synthesis damage induced by a distant local inflammation 1) is transmitted through the afferent C fibers, 2) makes glutamatergic synaptic connections with the preganglionic neurons of the sympathetic system, and 3) involves spinal and supraspinal pathways.

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Activity-dependent variations in conduction velocity of C fibers of rat sciatic nerve

Neuroscience Research ◽

10.1016/0168-0102(94)90084-1 ◽

1994 ◽

Vol 19 (4) ◽

pp. 427-431 ◽

Cited By ~ 1

Author(s):

Hyung-Cheul Shin ◽

Yun-Lyul Lee ◽

Hyeok-Yil Kwon ◽

Hyoung Jin Park ◽

Stephen A. Raymond

Keyword(s):

Sciatic Nerve ◽

Conduction Velocity ◽

Rat Sciatic Nerve ◽

C Fibers ◽

Activity Dependent

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A modified “triangular pulse” stimulator for C-fibers stimulation

Journal of Neuroscience Methods ◽

10.1016/0165-0270(91)90127-l ◽

1991 ◽

Vol 37 (2) ◽

pp. 169-172 ◽

Cited By ~ 7

Author(s):

F.-S. Jaw ◽

C.-T. Yen ◽

H.W. Tsao ◽

H.J. Yu

Keyword(s):

Triangular Pulse ◽

C Fibers

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

Journal of Neurosurgery ◽

10.3171/jns.1972.36.5.0569 ◽

1972 ◽

Vol 36 (5) ◽

pp. 569-583 ◽

Cited By ~ 34

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.

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