Sensitization of nociceptive C-fibers in zinc-deficient rats

1995 ◽  
Vol 268 (6) ◽  
pp. R1423-R1428 ◽  
Author(s):  
H. Izumi ◽  
H. Mori ◽  
T. Uchiyama ◽  
S. Kuwazuru ◽  
Y. Ozima ◽  
...  
Keyword(s):  
Substance P ◽  
Zinc Concentration ◽  
Leukotriene B4 ◽  
Plasma Extravasation ◽  
Deficient Diet ◽  
C Fibers ◽  
Pge2 Concentration ◽  
Antidromic Vasodilatation ◽  
C Fiber ◽  
Zinc Deficient Diet

A marked decrease in zinc concentration was observed in plasma (P < 0.001), hindpaw skin (P < 0.01), and dorsal skin (P < 0.01) in zinc-deficient rats (rats fed a zinc-deficient diet for 3 wk), compared with the control rats fed the same zinc-deficient diet supplemented with ZnCO3 (50 mg/kg diet). The threshold intensity needed to elicit vasodilatation in the hindpaw skin of the zinc-deficient rats on electrical stimulation of the saphenous nerve in a peripheral direction was markedly lower (P < 0.01) than that in the control rats. No difference was observed between control (n = 5) and zinc-deficient rats (n = 5) in the magnitude of the plasma extravasation evoked by either histamine or substance P. There was no difference between control and zinc-deficient rats in terms of the dose-response curve for release of histamine by substance P. Prostaglandin E2 (PGE2) concentration in the hindpaw skin of the zinc-deficient rats was nearly fourfold higher (P < 0.01) than that of the control rats, whereas no difference in the leukotriene B4 level in the hindpaw skin was observed between control and zinc-deficient rats. From the present study, it seems likely that an increased level of PGE2 in the vicinity of the nociceptive C-fiber terminals in the hindpaw skin of zinc-deficient rats may sensitize the terminals of the nociceptive C-fibers of the saphenous afferent nerve in the hindpaw and thus facilitate the production of antidromic vasodilatation.

Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat

1988 ◽  
Vol 60 (2) ◽  
pp. 438-445 ◽  
Author(s):  
H. A. Martin ◽  
A. I. Basbaum ◽  
E. J. Goetzl ◽  
J. D. Levine
Keyword(s):  
Acetic Acid ◽  
Glacial Acetic Acid ◽  
Leukotriene B4 ◽  
Thermal Stimulation ◽  
Mechanical Stimuli ◽  
Noxious Heat ◽  
C Fibers ◽  
Mechanical Threshold ◽  
C Fiber ◽  
Heat Threshold

1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.

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.

Enhanced lung C-fiber responsiveness in sensitized adult guinea pigs exposed to chronic tobacco smoke

2001 ◽  
Vol 91 (4) ◽  
pp. 1645-1654 ◽  
Author(s):  
Dale R. Bergren
Keyword(s):  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Airway Responsiveness ◽  
Compressed Air ◽  
Sensory Receptor ◽  
Plasma Extravasation ◽  
C Fibers ◽  
C Fiber

Tobacco smoke (TS) exposure induces bronchoconstriction and increases airway secretions and plasma extravasation in certain sensitive individuals, particularly those with asthma. C-fiber activation also induces these effects. Although the mechanism by which chronic TS exposure induces airway dysfunction is not well understood, TS exposure may enhance C-fiber responsiveness. To investigate the effect of chronic TS exposure on C-fiber responsiveness to capsaicin and bradykinin, especially in atopic individuals, we exposed ovalbumin (OA)-sensitized guinea pigs to TS (5 mg/l air, 30 min/day for 7 days/wk) or to compressed air. Nonsensitized guinea pigs were also exposed to either compressed air or TS. Beginning after 120 days of exposure, C fibers and rapidly adapting receptors (RARs) were challenged with capsaicin and bradykinin. TS exposure enhanced sensory receptor and airway responsiveness to both intravenous capsaicin and bradykinin challenge. C-fiber, RAR, and airway responsiveness to capsaicin challenge was greatest in OA-sensitized guinea pigs exposed to TS. OA alone induced capsaicin hyperresponsiveness at 5 μg. Airway responsiveness to bradykinin was also greatest in OA-sensitized guinea pigs exposed to TS. OA alone enhanced C-fiber responsiveness to bradykinin at 5 and 10 μg. C-fiber activation by either agonist appeared direct, whereas RAR activation appeared indirect. Therefore, a mechanism of airway hyperirritability induced by the combination of OA sensitization and chronic TS exposure may include hyperirritability of lung C fibers.

ZINC, COPPER AND MANGANESE DEFICIENCIES AND THE RUMINANT SKELETON: A REVIEW

1980 ◽  
Vol 60 (3) ◽  
pp. 579-590 ◽  
Author(s):  
M. HIDIROGLOU
Keyword(s):  
Structural Integrity ◽  
Zinc Concentration ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Active Role ◽  
Deficient Diet ◽  
Prominent Symptom ◽  
Zinc Deficient Diet ◽  
Bone Abnormalities ◽  
Cattle And Sheep

This review deals with changes in the morphology and composition of the skeleton of ruminants caused by trace element deficiencies, specifically with respect to zinc, copper and manganese. When ruminants are fed a zinc-deficient diet, bone abnormalities occur. Zinc is also reported to be of value in the prevention or cure of footrot in cattle and sheep. Depletion of zinc reserves appears to lead to alterations in bone mineralization and reduction of bone zinc concentration. The bones of copper-deficient ruminants are fragile and easily broken. The most prominent symptom of this deficiency is a very marked stiffness of the legs. Copper-deficient animals show symptoms of rickets with beading of the ribs and enlargement of the ends of the long bones. Histologically, the affected bones show widening of the growth plate and the overall appearance of the lesion is that of osteoporosis. Crosslinking between collagen precursors is impaired in copper deficiency, which affects the structural integrity of collagen. There is no evidence of any correlation between the concentration of copper in bone and the severity of malformation. A relationship between low manganese intake by gestating ruminants and increased incidence of deformed calves or lambs has been demonstrated. The deformities observed included enlarged joints and twisted forelimbs. Histological examinations of the affected bones revealed retarded growth. Since manganese plays an active role in bone matrix formation, synthesis of mucopolysaccharide is reduced in the deficient bones. The synthesis of chondroitin sulfate, which is involved in maintaining the rigidity of connective tissue, is also affected during manganese deficiency, resulting in skeletal abnormalities.

Substance P, 5-hydroxytryptamine, and bradykinin stimulate abdominal visceral afferents

1986 ◽  
Vol 250 (3) ◽  
pp. R465-R473 ◽  
Author(s):  
W. Y. Lew ◽  
J. C. Longhurst
Keyword(s):  
Substance P ◽  
Splanchnic Nerve ◽  
Gastrointestinal System ◽  
Visceral Afferents ◽  
Mechanical Stimuli ◽  
Descending Thoracic Aorta ◽  
C Fibers ◽  
Chemically Induced ◽  
C Fiber ◽  
Sensory Endings

To determine if chemicals produced endogenously within the gastrointestinal system stimulate abdominal visceral sensory endings, we recorded the response of 42 A- and 25 C-fibers in the splanchnic nerve of cats as substance P (10-20 micrograms), 5-hydroxytryptamine (5-HT, 100-200 micrograms), or bradykinin (10 micrograms) was injected into the descending thoracic aorta. Approximately half of the sensory endings responded to each chemical. However, significantly more C- than A-fiber endings responded to 5-HT (64 vs. 39%) and bradykinin (76 vs. 41%). Most C-fiber endings were insensitive to external mechanical stimuli, supporting the concept that these endings are primarily chemosensitive. In contrast, most A-fiber endings were quite sensitive to external mechanical stimuli. Additionally, more A-fiber endings located in contractile (gut or vasculature) than in noncontractile (pancreas, liver, or spleen) regions responded to 5-HT (58 vs. 19%), bradykinin (67 vs. 15%), and substance P (57 vs. 29%), a response that frequently occurred coincident with the development of chemically induced gut contractions. Thus many A-fiber endings are primarily sensitive to mechanical stimuli. However, 15-30% of the A-fiber endings located in noncontractile regions responded to chemicals, although the endings likely were removed from the mechanical effects of these chemicals. Since these A-fiber endings are also quite sensitive to external mechanical stimuli, they may be polymodal in their function. We conclude that abdominal visceral sensory endings are not homogeneous in function and are stimulated by several chemicals produced endogenously within the gastrointestinal system, including substance P, 5-HT, and bradykinin.

Capsaicin's Effect on Rat Nasal Mucosa Substance P Release: Experimental Basis for Vasomotor Rhinitis Treatment

1997 ◽  
Vol 11 (4) ◽  
pp. 313-316 ◽  
Author(s):  
Frederick A. Kuhn ◽  
Sergio Gonzalez ◽  
Magdalena Rodriguez ◽  
Carlos Cuilty Siller ◽  
Venetia Zachariou ◽  
...  
Keyword(s):  
Substance P ◽  
Nasal Mucosa ◽  
Stimulus Change ◽  
Nerve Fibers ◽  
Nasal Secretion ◽  
Plasma Extravasation ◽  
Vasomotor Rhinitis ◽  
C Fibers ◽  
P Release ◽  
Substance P Release

Substance P (SP) is one of several neuropeptides found in nasal mucosa. It exists primarily in sensory afferent neurons, which are best demonstrated by immunohistochemical staining. These substance P-like immunoreactive (SPLI) nerve fibers are unmyelinated C fibers, which connect to the trigeminal ganglion and the spinal trigeminal nucleus. They are found around vessels and seromucinous glands in the submucosa. When the nasal mucosa receives a noxious stimulus, SP is released and acts orthodromically as a comediator of nasal pain, while antidromically it induces vasodilatation, plasma extravasation, mucosal edema, and rhinorrhea. Its antidromic effects have been implicated in vasomotor rhinitis and can be blocked by topical intranasal capsaicin application. Wolf and others have demonstrated in human subjects that vasomotor rhinitis can be blocked up to 1 year by a series of intranasal capsaicin applications. It has not yet been demonstrated that nasal mucous SP levels following noxious nasal stimulus change after intranasal capsaicin pretreatment. Consequently, a project was designed to determine whether intranasal capsaicin pretreatment would affect nasal substance P release measured in nasal secretion. Nasal secretion SP levels were measured before and after noxious nasal stimulus in controls and in capsaicin pretreated rats. The difference in measured nasal secretion SP levels were significant (p < 0.05).

scholarly journals Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs

2006 ◽  
Vol 100 (6) ◽  
pp. 1918-1927 ◽  
Author(s):  
Dale R. Bergren
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Prostaglandin E ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Before And After ◽  
Acid Metabolites ◽  
Series Of Experiments

Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperresponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg9-[Leu8]-BK (10−3 M, B1 antagonist), and HOE-140 (10−4 M, B2 antagonist). After antagonist administration, BK increased neither PIP nor FA. Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a second series of experiments, Cap and SP were injected before and after infusion of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers through release of arachidonic acid metabolites. Indomethacin administration decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA or PIP was not altered by indomethacin. In subsequent experiments, C fibers were activated by prostaglandin E2 and F2α. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.

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.

Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output

2000 ◽  
Vol 279 (4) ◽  
pp. R1215-R1223 ◽  
Author(s):  
T. Mutoh ◽  
A. C. Bonham ◽  
J. P. Joad
Keyword(s):  
Substance P ◽  
Solitary Tract ◽  
C Fibers ◽  
Arterial Blood ◽  
Tracheal Pressure ◽  
C Fiber ◽  
Before And After ◽  
Neurokinin 1 ◽  
Central Synapses ◽  
Nerve Discharge

Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 μM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.

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.

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