Neurogenically Mediated Plasma Extravasation in Dura Mater: Effect of Ergot Alkaloids: A Possible Mechanism of Action in Vascular Headache

Cephalalgia ◽  
1988 ◽  
Vol 8 (2) ◽  
pp. 83-91 ◽  
Author(s):  
Stephen Markowitz ◽  
Kiyoshi Saito ◽  
Michael A Moskowitz
Keyword(s):  
Dura Mater ◽  
Sensory Nerve ◽  
Ergot Alkaloids ◽  
Nerve Fibers ◽  
Neurokinin A ◽  
Acute Administration ◽  
Plasma Extravasation ◽  
C Fibers ◽  
C Fiber ◽  
Stimulation Of

C-fiber- dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber- independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.

Relationships between permeable vessels, nerves, and mast cells in rat cutaneous neurogenic inflammation

1990 ◽  
Vol 68 (6) ◽  
pp. 2305-2311 ◽  
Author(s):  
J. N. Baraniuk ◽  
M. L. Kowalski ◽  
M. A. Kaliner
Keyword(s):  
Electrical Stimulation ◽  
Mast Cells ◽  
Neurogenic Inflammation ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Neurokinin A ◽  
Rat Skin ◽  
Protein Extravasation ◽  
Stimulation Of

Electrical stimulation of rat sensory nerves produces cutaneous vasodilation and plasma protein extravasation, a phenomenon termed “neurogenic inflammation”. Rat skin on the dorsum of the paw developed neurogenic inflammation after electrical stimulation of the saphenous nerve. In tissue sections, the extravasation of the supravital dye monastral blue B identified permeable vessels. Mast cells were identified by toluidine blue stain. Permeable vessels were significantly more dense in the superficial 120 microns of the dermis than in the deeper dermis, whereas mast cells were significantly more frequent in the deeper dermis. The relationships between nociceptive sensory nerve fibers, permeable vessels, and mast cells were examined by indirect immunohistochemistry for calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and substance P (SP). CGRP-, NKA-, and SP-containing nerves densely innervated the superficial dermis and appeared to innervate the vessels that became permeable during neurogenic inflammation. In contrast, mast cells were not associated with either permeable vessels or nerve fibers. These data suggest that electrical stimulation of rat sensory nerves produces vascular permeability by inducing the release of neuropeptides that may directly stimulate the superficial vascular bed. Mast cells may not be involved in this stage of cutaneous neurogenic inflammation in rat skin.

Pearls and pitfalls in experimental in vivo models of migraine: Dural trigeminovascular nociception

Cephalalgia ◽  
2013 ◽  
Vol 33 (8) ◽  
pp. 577-592 ◽  
Author(s):  
Simon Akerman ◽  
Philip R Holland ◽  
Jan Hoffmann
Keyword(s):  
Dura Mater ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Trigeminal Nucleus ◽  
Neuronal Activation ◽  
Trigeminovascular System ◽  
In Vivo Models ◽  
Doppler Flowmetry ◽  
Trigeminal Nucleus Caudalis ◽  
Stimulation Of

Background Migraine is a disorder of the brain and is thought to involve activation of the trigeminovascular system, which includes the peripheral afferent projection to the nociceptive specific dura mater, as well as the central afferent projection to the trigeminal nucleus caudalis. Stimulation of the blood vessels of the dura mater produces pain in patients that is referred to the head similar to headache. Headache mechanisms The likely reason for the pain is because the vascular structures of the dura mater, including the superior sagittal sinus and middle meningeal artery, are richly innervated by a plexus of largely unmyelinated sensory nerve fibers from the ophthalmic division of the trigeminal ganglion. Methodology Stimulation of these nociceptive specific nerve fibers is painful and produces neuronal activation in the trigeminal nucleus caudalis. Preclinical models of headache have taken advantage of this primarily nociceptive pathway, and various animal models use dural trigeminovascular nociception to assay aspects of head pain. These assays measure responses at the level of the dural vasculature and the central trigeminal nucleus caudalis as a correlate of trigeminovascular activation thought to be involved in headache. Summary This review will summarize the history of the development of models of dural trigeminovascular nociception, including intravital microscopy and laser Doppler flowmetry at the level of the vasculature, and electrophysiology and Fos techniques used to observe neuronal activation at the trigeminal nucleus caudalis. It will also describe some of pitfalls of these assays and developments for the future.

C-Fiber Depletion Alters Response Properties of Neurons in Trigeminal Nucleus Principalis

1999 ◽  
Vol 81 (2) ◽  
pp. 435-446 ◽  
Author(s):  
C. L. Kwan ◽  
J. A. Demaro ◽  
J. W. Hu ◽  
M. F. Jacquin ◽  
B. J. Sessle
Keyword(s):  
Functional Properties ◽  
Response Magnitude ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Trigeminal Nucleus ◽  
Response Properties ◽  
C Fibers ◽  
C Fiber ◽  
Nucleus Principalis ◽  
Stimulation Of

Kwan, C. L., J. A. Demaro, J. W. Hu, M. F. Jacquin, and B. J. Sessle. C-fiber depletion alters response properties of neurons in trigeminal nucleus principalis. J. Neurophysiol. 81: 435–446, 1999. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of vibrissa-sensitive low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal nucleus principalis were examined in adult rats. Neonatal rats were injected either with capsaicin or its vehicle within 48 h of birth. The depletion of unmyelinated afferents was confirmed by the significant decrease in plasma extravasation of Evan's blue dye induced in the hindlimb skin of capsaicin-treated rats by cutaneous application of mustard oil and by the significant decrease of unmyelinated fibers in both the sciatic and infraorbital nerves. The mechanoreceptive field (RF) and response properties of 31 vibrissa-sensitive neurons in capsaicin-treated rats were compared with those of 32 vibrissa-sensitive neurons in control (untreated or vehicle-treated) rats. The use of electronically controlled mechanical stimuli allowed quantitative analysis of response properties of vibrissa-sensitive neurons; these included the number of center- and surround-RF vibrissae within the RF (i.e., those vibrissae which when stimulated elicited ≥1 and <1 action potential per stimulus, respectively), the response magnitude and latency, and the selectivity of responses to stimulation of vibrissae in different directions with emphasis on combining both the response magnitude and direction of vibrissal deflection in a vector analysis. Neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae, in the number of center-RF vibrissae per neuronal RF, and in the percentage of vibrissa-sensitive neurons that also responded to stimulation of other types of orofacial tissues. Compared with control rats, capsaicin-treated rats showed significant increases in the response magnitude to stimulation of surround-RF vibrissae as well as in response latency variability to stimulation of both center- and surround-RF vibrissae. C-fiber depletion also significantly altered the directional selectivity of responses to stimulation of vibrissae. For neurons with multiple center-RF vibrissae, the proportion of center-RF vibrissae with net vector responses oriented toward the same quadrant was significantly less in capsaicin-treated compared with control rats. These changes in the functional properties of principalis vibrissa-sensitive neurons associated with marked depletion of C-fiber afferents are consistent with similarly induced alterations in LTM neurons studied at other levels of the rodent somatosensory system, and indeed may contribute to alterations previously described in the somatosensory cortex of adult rodents. Furthermore, these results provide additional support to the view that C fibers may have an important role in shaping the functional properties of LTM neurons in central somatosensory pathways.

Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions

Neuroscience ◽  
1997 ◽  
Vol 77 (3) ◽  
pp. 829-839 ◽  
Author(s):  
V Dimitriadou ◽  
A Rouleau ◽  
M.D Trung Tuong ◽  
G.J.F Newlands ◽  
H.R.P Miller ◽  
...  
Keyword(s):  
Mast Cells ◽  
Dura Mater ◽  
Sensory Nerve ◽  
Nerve Fibers ◽  
Functional Relationships ◽  
Inflammatory Conditions

Endogenous BK stimulates ischemically sensitive abdominal visceral C fiber afferents through kinin B2 receptors

1994 ◽  
Vol 267 (6) ◽  
pp. H2398-H2406 ◽  
Author(s):  
H. L. Pan ◽  
G. L. Stahl ◽  
S. V. Rendig ◽  
O. A. Carretero ◽  
J. C. Longhurst
Keyword(s):  
Receptor Antagonist ◽  
Impulse Activity ◽  
Discharge Rate ◽  
Visceral Afferents ◽  
C Fibers ◽  
C Fiber ◽  
Hoe 140 ◽  
B2 Receptors ◽  
The Right ◽  
Stimulation Of

Abdominal ischemia and reperfusion reflexly activate the cardiovascular system. In the present study, we evaluated the role of endogenously produced bradykinin (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of abdominal ischemia. Abdominal ischemia increased the portal venous plasma BK level from 49 +/- 10 to 188 +/- 66 pg/ml (P < 0.05). Injection of BK (1 microgram/kg ia) into the descending aorta significantly increased impulse activity (0.88 +/- 0.16 impulses/s) of 10 C fibers, whereas a kinin B1-receptor agonist, des-Arg9-BK (1 microgram/kg), did not alter the discharge rate. Inhibition of kininase II activity with captopril (4 mg/kg i.v.) potentiated impulse activity of 14 ischemically sensitive C fibers (0.44 +/- 0.09 vs. precaptopril, 0.33 +/- 0.08 impulses/s; P < 0.05). In addition, a kinin B2-receptor antagonist (NPC-17731; 40 micrograms/kg i.v.) attenuated activity of afferents during ischemia (0.39 +/- 0.08 vs. pre-NPC-17731, 0.72 +/- 0.13 impulses/s; P < 0.05) and eliminated the response of 10 C fibers to BK. Another kinin B2-receptor antagonist, Hoe-140 (30 micrograms/kg iv), had similar inhibitory effects on six other ischemically sensitive C fibers. In 15 separate cats treated with aspirin (50 mg/kg i.v.), Hoe-140 (30 micrograms/kg i.v.) attenuated impulse activity of only 3 of 16 ischemically sensitive C fibers. These data suggest that BK produced during abdominal ischemia contributes to the stimulation of ischemically sensitive visceral C fiber afferents through kinin B2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary C-fibers reflexly increase secretion by tracheal submucosal glands in dogs

1985 ◽  
Vol 58 (3) ◽  
pp. 907-910 ◽  
Author(s):  
H. D. Schultz ◽  
A. M. Roberts ◽  
C. Bratcher ◽  
H. M. Coleridge ◽  
J. C. Coleridge ◽  
...  
Keyword(s):  
Gland Secretion ◽  
Right Atrial ◽  
Vagus Nerves ◽  
C Fibers ◽  
Airway Secretion ◽  
Submucosal Glands ◽  
C Fiber ◽  
Anesthetized Dogs ◽  
The Right ◽  
Stimulation Of

Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10–20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.

scholarly journals Stimulation of vagal pulmonary C fibers by inhaled wood smoke in rats

1998 ◽  
Vol 84 (1) ◽  
pp. 30-36 ◽  
Author(s):  
C. J. Lai ◽  
Y. R. Kou
Keyword(s):  
Hydroxyl Radical ◽  
Combined Treatment ◽  
Wood Smoke ◽  
Radical Scavenger ◽  
C Fibers ◽  
Hydroxyl Radical Scavenger ◽  
C Fiber ◽  
Delayed Phase ◽  
Stimulation Of ◽  
Sustained Increase

Lai, C. J., and Y. R. Kou. Stimulation of vagal pulmonary C fibers by inhaled wood smoke in rats. J. Appl. Physiol. 84(1): 30–36, 1998.—This study investigated the stimulation of vagal pulmonary C fibers (PCs) by wood smoke. We recorded impulses from PCs in 58 anesthetized, open-chest, and artificially ventilated rats and delivered 6 ml of wood smoke into the lungs. Within 1 or 2 s after the smoke delivery, an intense and nonphasic burst of discharge [Δ = +7.4 ± 0.7 (SE) impulses/s, n = 68] was evoked in 60 of the 68 PCs studied and lasted for 4–8 s. This immediate stimulation was usually followed by a delayed and more sustained increase in C-fiber activity (Δ = +2.0 ± 0.4 impulses/s). The overall stimulation was not influenced by removal of smoke particulates ( n = 15) or by pretreatment with vehicle ( n = 8) for dimethylthiourea (DMTU; a hydroxyl radical scavenger) or indomethacin (Indo; a cyclooxygenase inhibitor). The immediate-phase stimulation was not affected by pretreatment with Indo ( n= 8) but was largely attenuated by pretreatment with DMTU ( n = 12) or by a combined treatment with DMTU and Indo (DMTU+Indo; n = 8). Conversely, the delayed-phase stimulation was partially suppressed either by DMTU or by Indo but was totally abolished by DMTU+Indo. These results suggest that 1) the stimulation of PCs is linked to the gas phase of wood smoke and 2) hydroxyl radical, but not cyclooxygenase products, is involved in the immediate-phase stimulation, whereas both metabolites are responsible for evoking the delayed-phase stimulation.

Blockade of the pressor response to muscle ischemia by sensory nerve block in man

1979 ◽  
Vol 237 (4) ◽  
pp. H433-H439 ◽  
Author(s):  
P. R. Freund ◽  
L. B. Rowell ◽  
T. M. Murphy ◽  
S. F. Hobbs ◽  
S. H. Butler
Keyword(s):  
Nerve Block ◽  
Pressor Response ◽  
Sensory Nerve ◽  
Sensory Block ◽  
Nerve Fibers ◽  
Dynamic Exercise ◽  
Sensory Blockade ◽  
Muscle Ischemia ◽  
Respiratory Responses ◽  
Stimulation Of

Differential nerve block from peridural anesthesia was used to determine a) if the pressor response to muscle ischemia in man is caused by stimulation of small sensory nerve fibers and b) if these fibers contribute to cardiovascular-respiratory responses during dynamic exercise. Four men exercised at 50-100 W for 5 min. Muscle ischemia and a sustained pressor response were produced by total circulatory occlusion of both legs beginning 30 s before the end of exercise and continuing for 3 min postexercise. During regression of full motor and sensory block, motor strength recovered while sensory block continued; the pressor response was blocked as long as sensory anesthesia persisted (two subjects). During blockade of the pressor response, cardiovascular-respiratory responses to exercise gradually returned from augmented to normal (preblock) levels. Sensory blockade was incomplete in two subjects and the pressor response was not fully blocked. We conclude that stimulation of small sensory fibers during ischemia elicits the pressor response, but that these fibers appear not to contribute to cardiovascular-respiratory responses during mild dynamic exercise with adequate blood flow.

Diaphragmatic responses to graded stimulation of pulmonary C-fibers with capsaicin

1985 ◽  
Vol 59 (5) ◽  
pp. 1487-1494 ◽  
Author(s):  
J. R. Coast ◽  
S. S. Cassidy
Keyword(s):  
Dose Response ◽  
Strain Gauge ◽  
Contraction Rate ◽  
C Fibers ◽  
C Fiber ◽  
Shallow Breathing ◽  
Fiber Stimulation ◽  
Rapid Shallow Breathing ◽  
Stimulation Of

It has been suggested that pulmonary C-fiber stimulation is responsible for the rapid shallow breathing that accompanies pulmonary edema. However, pulmonary C-fiber stimulation also causes apnea. To determine whether it was possible for both responses to occur from one stimulus, we infused varying concentrations of capsaicin (a compound that selectively stimulates C-fiber receptors in the dog) into an in situ vascularly isolated dog lung and measured rates and strengths of diaphragmatic contractions with a strain gauge sutured to the diaphragm and electromyogram electrodes implanted in the diaphragm. There was a dose response to capsaicin in that increased doses were related directly with the duration of cessation of diaphragmatic contractions (2–100 s) and inversely with the latency from the start of stimulation to the beginning of the cessation of diaphragmatic contractions (100–5 s). There was no evidence, however, of rapid shallow breathing in this set of experiments. Either a gradual return to normal rate from prolonged contraction intervals or no change in contraction rate was seen, depending on capsaicin concentration. We conclude that the primary diaphragmatic response to pulmonary C-fiber stimulation is a cessation of diaphragmatic contractions rather than rapid shallow contractions.

Neuroplastic effects of neonatal capsaicin on neurons in adult rat trigeminal nucleus principalis and subnucleus oralis

1996 ◽  
Vol 75 (1) ◽  
pp. 298-310 ◽  
Author(s):  
C. L. Kwan ◽  
J. W. Hu ◽  
B. J. Sessle
Keyword(s):  
Functional Properties ◽  
Mustard Oil ◽  
Blue Dye ◽  
Plasma Extravasation ◽  
Adult Rats ◽  
Response Properties ◽  
Adult Rat ◽  
C Fibers ◽  
C Fiber ◽  
Nucleus Principalis

1. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal (V) subnucleus oralis and nucleus principalis were examined. Neonatal rats were injected with capsaicin within 48 h of birth. The mechanoreceptive field (RF) and response properties of 184 oralis LTM neurons and 185 principalis LTM neurons were studied in adult capsaicin-treated rats. These properties were compared with those of 200 oralis LTM neurons and 253 principalis LTM neurons from untreated or vehicle-treated (control) adult rats. 2. The effectiveness of neonatal capsaicin in depleting C fibers was tested by determining the plasma extravasation of Evans blue dye that was induced in the hindlimb skin by the cutaneous application of the C-fiber excitant and inflammatory irritant mustard oil. The amount of extravasation in capsaicin-treated rats was significantly less than that of control rats. 3. Neonatal capsaicin treatment was associated with significant increases in neuronal RF size and in the percentage of neurons with convergent inputs from more than one type of peripheral tissue (e.g., nonsinus hair, vibrissae, glabrous skin/mucosa, subcutaneous structures such as joint or muscle, periodontal ligament) in both subnucleus oralis and nucleus principalis. In subnucleus oralis, neonatal capsaicin treatment produced a significant increase in the percentage of neurons with a RF involving both V1 and V2 divisions, and a significant decrease in the percentage of neurons with a RF restricted to the V1 division. Analogous changes were not observed in nucleus principalis, although for principalis vibrissa-sensitive neurons, neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae per neuronal RF and in the maximal length of the vibrissal row (i.e., the number of vibrissae in the longest row of vibrissae, stimulation of which was effective in activating a given neuron). 4. Neonatal capsaicin treatment did not significantly affect other oralis or principalis neuronal properties, including the percentage of neurons exhibiting spontaneous activity or abnormal response properties (such as habituating tap sensitivity, discontinuous RF, or mixed adaptation properties within the RF). 5. The changes in the functional properties of oralis and principalis LTM neurons induced by neonatal capsaicin treatment are consistent with those previously reported at other levels of the rodent CNS. They provide additional support to the view that C fibers may have an important role in shaping the functional properties of central LTM somatosensory neurons.

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