Biomedical subjects

S R White

Publications and source records attributed to S R White.

At least 19 recordsLinked to original sources

PubMed1992

Prazosin suppresses development of axonal damage in rats inoculated for experimental allergic encephalomyelitis.

The effectiveness of the alpha 1-adrenergic antagonist prazosin for preventing monoaminergic axonal damage in the spinal cords of rats that were inoculated for experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Prazosin injections (2 mg, i.p.) given twice daily from day 7 to day 15 postinoculation significantly reduced paralysis, spinal cord inflammation and monoaminergic axonal damage compared to saline injections. A close positive correlation between severity of inflammation and severity of axonal damage was found for both prazosin- and saline-treated rats that were inoculated for EAE. These findings confirmed previous observations of suppression of the development of clinical signs of EAE by prazosin treatment and supported the hypothesis that some factor associated with spinal cord inflammation may be responsible for the bulbospinal monoaminergic axonal damage that occurs during EAE.

Animals↗

PubMed1992

Direct effects on airway smooth muscle contractile response caused by endothelin-1 in guinea pig trachealis.

Endothelin-1 (ET-1), a peptide derived from vascular endothelial cells, causes tracheal smooth muscle (TSM) relaxation followed by sustained contraction when administered intravenously in guinea pigs by a mechanism that depends upon an intact airway epithelium. To elucidate the potential role of the epithelium in modulating the response to ET-1 and the potential effects of local release of ET-1, we studied the effects of topical application of ET-1 to a segment of TSM in situ. An epithelium smooth muscle preparation that does not disrupt normal anatomic relationships was used; smooth muscle contraction was measured isometrically in vivo. Application of 10(-10) mol/cm2 ET-1 to the epithelial surface in six animals caused 2.27 +/- 0.45 g/cm active tension (AT) of the TSM segment after 30 min (p less than 0.05 versus baseline); an initial relaxation response was not observed. Endothelin-1 was dose-dependent and was 1,000 times more potent than acetylcholine in causing AT in TSM. Pretreatment with ET-1 did not alter the subsequent response to acetylcholine. Contraction elicited by topical application of ET-1 persisted greater than 3 h. In five animals in which the epithelium was removed, 10(-10) mol/cm2 ET-1 caused 4.45 +/- 0.92 g/cm AT after 30 min (p less than 0.05 versus intact epithelium). These data suggest that topical application of ET-1 elicits responses that are different from those elicited in the same preparation after intravenously administered ET-1: (1) TSM contraction that is not preceded by a transient relaxation phase, and (2) contraction that is not reduced after removal of the epithelium.

Acetylcholine↗

PubMed1992

Direct effects and augmentation of airway smooth muscle contraction caused by phospholipase A2.

We examined the effect of phospholipase A2 (PLA2; Naja naja) on isometric tracheal smooth muscle force generation in guinea pig trachealis in situ. Direct application of PLA2 to the surface of the trachea caused dose-related contraction of tracheal smooth muscle. In seven guinea pigs, a dose/density of 100 micrograms/cm2 PLA2 caused active tension (AT) that began immediately and was maximum (1.32 +/- 0.13 g/cm) at 5 min (p less than 0.01 versus baseline tension). PLA2 also augmented the contractile response to intravenously administered acetylcholine (ACh); AT caused by 3 x 10(-7) mol/kg ACh was 0.98 +/- 0.13 g/cm after PLA2 versus 0.64 +/- 0.09 g/cm in control animals (p = 0.003). PLA2 inactivated with bromophenacyl bromide (BPB) prior to topical application neither caused contraction (-0.18 +/- 0.18 g/cm AT, p = NS versus baseline tension) nor altered muscarinic responsiveness to 3 x 10(-7) mol/kg ACh. Contraction caused by 100 micrograms/cm2 PLA2 was greater after epithelium removal (2.73 +/- 0.40 g/cm AT versus 1.32 +/- 0.13 g/cm AT in epithelium-intact animals, p less than 0.005). However, epithelium removal (confirmed histologically) attenuated completely augmentation of muscarinic contraction caused by PLA2. Augmentation of muscarinic contraction also was blocked with 15 mg/kg 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW 755c), an inhibitor of eicosanoid synthesis, administered intravenously 30 min prior to topical application of 100 micrograms/cm2 PLA2. In contrast, contraction of tracheal smooth muscle caused by PLA2 was not affected significantly by blockade of eicosanoid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1992

Topographic distribution of prostaglandin secretion caused by bradykinin in canine tracheal epithelial cells.

Inflammatory mediators promote the synthesis and secretion of prostaglandin (PG) mediators in airway epithelial cells. In this study, we examined the topographic and kinetic profile of PG secretion in canine tracheal epithelial cells harvested from the tracheal posterior membrane (PM) and those obtained from the immediately anterior cartilage-associated membrane (CM). Primary cultures of tracheal epithelial cells obtained from 23 disease-free dogs were grown to confluence in serum-enriched medium. Cells then were incubated in serum-free medium for 1 h and stimulated with 10(-7) to 10(-5) M bradykinin. Baseline secretion of PGE2 was similar to both PM and CM cells; however, PM cells secreted greater concentrations in both PGI2 (measured as 6-keto-PGF1 alpha) (1,269 +/- 160 versus 775 +/- 91 pg/10(6) cells, P less than 0.01) and PGF2 alpha (436 +/- 54 versus 234 +/- 45 pg/10(6) cells, P less than 0.002) compared with CM cells. Bradykinin (BK) stimulation caused substantial secretion in less than or equal to 20 min of PGE2 and 6-keto-PGF1 alpha from PM but not CM cells: after stimulation with 10(-6) M BK, 6-keto-PGF1 alpha secretion was 348 +/- 74% in PM cells versus 157 +/- 18% of baseline secretion in CM cells (P less than 0.005); PGE2 secretion was 310 +/- 53% in PM cells versus 163 +/- 15% of baseline secretion in CM cells (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Oxygen metabolism and catecholamine secretion during chloralose anesthesia in lambs.

Anesthetic agents are required when restraining animals in most forms of animal research. In particular, alpha-chloralose is a widely used anesthetic for respiratory and cardiovascular research despite limited controlled studies investigating whether chloralose could represent a variable influencing cardiorespiratory reflexes in acute animal studies. We previously used a chronically-instrumented neonatal lamb model to determine that chloralose had important effects on oxygen delivery and on basal hemodynamics. To investigate the influence of chloralose on oxygen metabolism and catecholamine secretion in relation to these hemodynamic changes, we studied 12 lambs before and after infusion of chloralose (30 mg/kg, i.v.) or control saline vehicle. Chloralose caused no differences in arterial or mixed venous oxygen contents, arterio-venous oxygen difference, or oxygen delivery, consumption, or extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1991

A kinetic assay for eosinophil peroxidase activity in eosinophils and eosinophil conditioned media.

The activity of eosinophil peroxidase (EPO) is commonly employed as a measure of eosinophil activation in biologic fluids. Determination of product formation by this enzyme by end-point measurement may be affected profoundly by substrate concentrations, reaction time and degradation of end-product and enzyme. To determine more accurately EPO concentrations in media conditioned by isolated, purified eosinophils, we have developed a kinetic, colorimetric assay to measure EPO concentration as a function of maximum velocity of reaction (Vmax). An automated method for determining Vmax in a 96-well microplate colorimetric assay was utilized over a wide range of substrate concentrations. Concentrations greater than or equal to 3 x 10(-8) g/ml could be determined reliably with this assay. Peroxidase activity was inhibited in a concentration-dependent manner by the addition of 3-amino-1,2,4-triazole (AMT). The EPO concentration in eosinophils determined by this kinetic method was approximately 1.1 x 10(-5) g/10(6) eosinophils. Eosinophil activation with 10(-6) M f-Met-Leu-Phe (fMLP) caused substantial EPO secretion (9.0 +/- 1.7% vs. 2.9 +/- 0.6% total EPO content for control, P = 0.05) and decrease in eosinophil EPO concentration (92.3 +/- 4.2% of control, P = 0.038). Secretion was enhanced by the addition of 5 micrograms/ml cytochalasin B to 10(-6) M fMLP (25.9 +/- 12.7% total EPO content, P = 0.043 vs. control); similar decreases were noted in eosinophil EPO concentration (71.7 +/- 16.1% of control, P = 0.043). These data demonstrate that determination of EPO secretion by measurement of Vmax is a reliable, accurate method for precise quantification of this enzyme in media containing purified eosinophils or eosinophil products in the absence of other forms of peroxidase activity.

Amitrole↗

PubMed1991

Effects of 5-hydroxytryptophan on extracellular serotonin in the spinal cord of rats with experimental allergic encephalomyelitis.

Serotonin (5-HT) and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were collected by in vivo dialysis in the lumbar spinal cord of control rats and rats with hindlimb paralysis induced by experimental allergic encephalomyelitis (EAE). Both 5-HT and 5-HIAA were significantly decreased in baseline samples from EAE rats compared to controls. This decrease in extracellular 5-HT and 5-HIAA in the EAE rats was accompanied by marked morphological changes in spinal cord axons and axon terminal plexuses that were stained for 5-HT-like immunoreactivity. The 5-HT precursor, 5-hydroxytryptophan (5-HTP)-increased 5-HT and 5-HIAA levels in dialysate samples from both control and EAE animals. However, the 5-HTP-induced increase in extracellular 5-HT was significantly greater in the EAE rats than in the controls, despite a lower baseline 5-HT level in the EAE animals. In contrast to 5-HT, both baseline and post-5-HTP levels of 5-HIAA were significantly higher in control animals than in EAE animals. The decreased extracellular 5-HT and 5-HIAA in baseline samples from the EAE rats compared to controls is probably a consequence of the damage to descending 5-HT axons and axon terminals that occurs during the disease. The larger increase in extracellular 5-HT in EAE animals after precursor injection may reflect both decreased 5-HT reuptake from the extracellular space by damaged 5-HT terminals and disruption of the blood-brain barrier that allows entry into the central nervous system of 5-HT that was synthesized from 5-HTP in the periphery.

5-Hydroxytryptophan↗

PubMed1991

Norepinephrine effects on spinal motoneurons.

Intracellular recordings from cat spinal motoneurons in situ demonstrated that microiontophoretic application of NE with low-intensity ejection currents produces a slowly developing, small-amplitude depolarization of the cells, in contrast to early reports of NE-induced hyperpolarization. This depolarization was associated with an increase in excitability of the cells and a decrease in membrane conductance. These observations are consistent with the hypothesis that NE reduces potassium conductance in spinal motoneurons as has been proposed for facial motoneurons (VanderMaelen and Aghajanian, 1980) and thalamic neurons (McCormick and Prince, 1988). The time course of the facilitatory effects of NE on cat motoneuron excitability recorded intracellularly agreed very closely with the time course of NE-induced facilitation of glutamate-evoked excitability in rat spinal motoneurons recorded extracellularly. The similarity of the observations in rats and cats suggests that NE functions generally to enhance mammalian motoneuron responsiveness to excitatory input.

Action Potentials↗

PubMed1991

Efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients.

OBJECTIVE: To determine the efficacy of daily routine chest radiographs in intubated, mechanically ventilated patients. DESIGN: With approval of our Institutional Review Board, data were collected prospectively to compare bedside clinical assessment of the patient with the routine chest radiograph in determining the occurrence of new findings. Before review of the daily chest film, patients underwent careful evaluation of clinical and physiologic variables by critical care physicians, who then documented the new findings and the diagnostic and therapeutic interventions required. These results were compared with the interpretations of the daily chest film by radiologists blinded to the clinical assessment. Correlations were made of the new major (requiring immediate intervention) and new minor (abnormal but not requiring immediate intervention) findings noted by clinical assessment and chest radiography. SETTING: This study was conducted in a ten-bed medical/surgical ICU admitting 650 to 750 patients/yr, a majority of whom require intubation and mechanical ventilation. PATIENTS: Seventy-seven episodes of intubation and mechanical ventilation in 74 patients were evaluated. Only patients with translaryngeal intubation and a requirement for mechanical ventilation beyond 24 hrs were considered for inclusion in this study. Major admitting diagnoses included malignancy, aspiration pneumonia, sepsis, liver failure, chronic obstructive pulmonary disease, and adult respiratory distress syndrome. INTERVENTIONS: Specific interventions were not made by study design; instead, clinical practice with and without the routine chest radiograph was compared. MEASUREMENTS AND MAIN RESULTS: The measure of comparison between the chest radiograph and clinical assessment was the correlation between the two for a number of major and minor findings defined in advance. A total of 538 chest radiographs were examined; of these, 354 (65.8%) did not disclose either new major or new minor findings as defined. One hundred sixty-three radiographs disclosed only new minor findings, 40.5% of which were anticipated by bedside assessment. However, in 13 (17.6%, 95% confidence interval 9% to 26%) of our 74 patients, new major findings were discovered only by chest radiography. CONCLUSIONS: These data demonstrate that, while a large percentage of radiographs will not disclose new findings, routine daily studies have a substantial impact on the management of intubated, mechanically ventilated patients in the ICU. These findings support the use of daily chest radiographs in critically ill patients.

Adolescent↗

PubMed1991

Epithelial modulation of airway smooth muscle response to endothelin-1.

We investigated the role of epithelial modulation of contraction caused by endothelin-1 in airway smooth muscle in guinea pigs in situ. Airway responses were assessed isometrically as tracheal force and simultaneously as change in lung resistance. Intravenous administration of 10(-8) mol/kg endothelin-1 caused a biphasic response in tracheal active tension: initial relaxation (-0.82 +/- 0.22 g/cm after 30 s, p less than 0.05 versus baseline) followed by contraction (1.65 +/- 0.28 g/cm after 7 min, p less than 0.05 versus baseline). Endothelin-1 also elicited immediate bronchoconstriction; lung resistance increased from 0.148 +/- 0.030 to 0.992 +/- 0.274 cm H2O/L/s (p less than 0.005) after 10(-8) mol/kg endothelin-1 given intravenously. Active tension elicited by 10(-8) mol/kg endothelin-1 after removal of the epithelium from the tracheal segment (0.59 +/- 0.16 g/cm) was less than in segments with an intact epithelium (1.65 +/- 0.28 g/cm, p less than 0.01). Both tracheal contraction and bronchoconstriction were attenuated by pretreatment with indomethacin orally, BW 755C intravenously, or substitution of endothelin-C-terminal hexapeptide for endothelin-1. However, the initial tracheal relaxation response was similar after each intervention. These data suggest actions of endothelin-1 that have not been demonstrated previously: (1) endothelin-1 elicits a biphasic response in tracheal smooth muscle (an initial relaxation response elicited by the carboxy-terminal residues and a later contractile response that requires synthesis of a cyclooxygenase mediator) and (2) epithelium adjacent to the airway smooth muscle modulates contraction elicited by endothelin-1.

Animals↗

PubMed1990

Damage to bulbospinal serotonin-, tyrosine hydroxylase-, and TRH-containing axons occurs early in the development of experimental allergic encephalomyelitis in rats.

Spinal cord monoaminergic and peptidergic axonal damage occurring during the development of experimental allergic encephalomyelitis (EAE) was assessed using immunohistochemistry. Spinal cord axons immunoreactive for serotonin, catecholamines, or a thyrotropin-releasing hormone marker peptide were found to be markedly swollen and distorted by the earliest stage of detectable paralysis during EAE development (the flaccid tail stage). As clinical signs progressed to complete hindlimb paralysis, axonal damage became increasingly extensive. Axonal damage was equally pronounced whether EAE was induced by inoculation with purified myelin basic protein or with whole spinal cord homogenate, suggesting that the damage did not result from an immune attack directed against specific monoaminergic and/or peptidergic antigens present in the inoculant. However, two observations suggested that mechanical or chemical factors associated with the inflammatory foci contribute to the axonal damage: first, distorted axons were nearly always located adjacent to blood vessels or the pial surface, sites at which inflammation occurs during EAE. Second, the severity of axonal damage correlated with the severity of the inflammation. The early onset of axonal damage during development of EAE and the close correlation that was found between the severity of axonal damage and the severity of clinical signs suggested that the axonal damage may contribute to the clinical signs of the disease.

Animals↗

PubMed1990

Receptor subtypes mediating facilitation by serotonin of excitability of spinal motoneurons.

Serotonin receptor ligands, with differential affinity for subtypes of serotonin (5-HT) receptors, were administered intravenously or iontophoretically to urethane-anesthetized rats and the effects of these compounds on glutamate-evoked firing of spinal motoneurons were tested. The excitability of spinal motoneurons was markedly enhanced after intravenous administration of the selective 5-HT1A ligand 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT) in rats with acute spinal transections at C1. However, local application of DPAT, directly into the ventral horn by microiontophoresis, inhibited the glutamate-evoked firing of motoneurons in direct contrast to the facilitatory effects of iontophoretically applied 5-HT. The DPAT-induced inhibition may have been nonspecific, since it was not antagonized by methysergide. Other 5-HT agonists, with relatively selective affinity for 5-HT1B, 5-HT1C and 5-HT2 receptors, increased the excitability of spinal motoneurons when applied iontophoretically or intravenously. The excitatory effect of iontophoretically applied 5-HT was antagonized by the nonselective 5-HT antagonist, methysergide and by ketanserin and ritanserin, which have relatively selective affinity for 5-HT1C and 5-HT2 receptors. These results indicate that 5-HT1A receptors do not mediate facilitation of excitability of motoneurons produced by local application of 5-HT directly into the vicinity of the motoneurons. However, the marked increase in firing of motoneurons that was caused by intravenous administration of DPAT in spinal transected rats, suggests that 5-HT1A receptors in the spinal cord may participate in 5-HT-induced enhancement of somatomotor outflow, at sites presynaptic to the motoneurons. The iontophoretic results suggest that 5-HT1B, 5-HT1C and 5-HT2 receptors may all play a role in facilitation of the excitability of spinal motoneurons by locally applied 5-HT. Differentiation between these subtypes of receptor awaits the development of more completely selective agonists and antagonists.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1990

Epithelium-dependent contraction of airway smooth muscle caused by eosinophil MBP.

We have identified two distinct functions of the epithelium of guinea pig airways that modulate airway smooth muscle contractility in the presence of the major basic protein (MBP) of human eosinophilic granules: 1) active force generation resulting less than 1 min after epithelial contact with MBP; and 2) sustained, augmented force generation that does not depend on cytotoxic interference with the synthesis of an epithelial-derived inhibitory factor. To evaluate these influences, an in situ preparation of guinea pig trachea was developed that permitted direct, on-line measurement of isometric force generation in the underlying muscle. Direct application of 10(-8) mol/cm2 MBP to the surface of the epithelium elicited force generation that did not require the presence of a contractile agonist. Force generation began less than 1 min after MBP application and reached maximum active tension (AT) of 0.97 +/- 0.38 g/cm at 30 min (P less than 0.05 vs. baseline). Denatured MBP did not elicit active tension. MBP also caused augmented contraction to intravenous acetylcholine (ACh); 30 min after topical application of MBP, AT generated by 3 x 10(-7) mol/kg iv ACh was 0.85 +/- 0.14 vs. 0.55 +/- 0.08 g/cm in control animals (P less than 0.05). Threshold response to ACh (-8.1 +/- 0.3 log mol/kg) also decreased significantly after MBP (-9.1 +/- 0.4 log mol/kg) vs. baseline (P less than 0.01). Removal of the epithelium (confirmed histologically) abolished both direct contraction and augmented force generation to ACh caused by topical application of MBP to the airway muscle. These data suggest actions of MBP that have not been demonstrated previously: 1) activation of epithelial function that causes direct contraction of airway smooth muscle; and 2) independence of the MBP-induced effects from active tone elicited by other agonists. We also demonstrate that augmented contraction that does not depend on MBP blockade of tonic inhibitory secretion from the epithelium.

Acetylcholine↗

PubMed1990

Sympathetic secretory response to hypercapnic acidosis in swine.

We studied the effect of graded acute hypercapnic acidosis (HA) on sympathetic neural activation in 15 juvenile farm swine in vivo. In seven animals with acute HA, plasma norepinephrine (NE) concentration increased progressively from 189 +/- 34 to 483 +/- 80 pg/ml (P less than 0.04) as arterial CO2 partial pressure (PaCO2) increased in steps from 40 to 80 Torr (pH 7.17 +/- 0.01). Plasma epinephrine (EPI) concentration increased from 30 +/- 15 to 125 +/- 66 pg/ml (P = NS) over the same change in PaCO2. At PaCO2 of 110 Torr, plasma NE increased 3.4-fold above maximal basal concentrations; plasma EPI was 1.8-fold greater than basal under the same conditions. With HA, systemic vascular resistance (SVR) decreased from 1,748 +/- 110 to 1,392 +/- 145 dyn.s.cm-5 (P less than 0.0002), cardiac output (CO) increased from 3.4 +/- 0.3 to 4.3 +/- 0.3 l/min (P less than 0.01), and heart rate (HR) increased from 117 +/- 11 to 154 +/- 17 beats/min (P less than 0.03). To demonstrate that catecholamine secretion was related directly to acidosis caused by an increase in PaCO2, HCO3- was infused in eight other swine to buffer extracellular acute HA (pH 7.37 +/- 0.01 at PaCO2 of 80 Torr). Buffering attenuated the increase in plasma NE, which remained within the normal range at PaCO2 of 80 Torr. The decrease in SVR and increases in CO and HR also were also attenuated by HCO3- buffering of HA. We demonstrate the effects of graded acute HA on endogenous secretion of catecholamine and on the associated hemodynamic responses in swine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

PubMed1989

Serotonin depolarizes cat spinal motoneurons in situ and decreases motoneuron afterhyperpolarizing potentials.

Mechanisms by which serotonin produces a long duration facilitation of spinal motoneuron excitability were investigated in decerebrate cats using intracellular recording combined with extracellular microiontophoresis. Serotonin was found to produce a slowly developing, small amplitude, long duration depolarization of the spinal motoneurons. This finding conflicts with early reports of serotonin-induced rapid hyperpolarization of cat spinal motoneurons, but exactly corresponds to more recent findings in rat facial motoneurons. The depolarization was accompanied by an increase in motoneuron excitability and an increase in membrane input resistance. In addition, serotonin reduced the motoneuron postspike afterhyperpolarizing potential in several motoneurons even through depolarization consistently occurred.

Action Potentials↗

PubMed1989

A comparison of 5-hydroxytryptophan effects on rat lumbar spinal cord serotonin release and monosynaptic response amplitude.

The physiological effects of injections of the serotonin precursor, 5-hydroxytryptophan (5-HTP) are thought to result from increased serotonin (5-HT) release, although release has not been directly measured in vivo. This study compared the effects of 5-HTP on rat lumbar spinal cord monosynaptic response (MSR) amplitude and on 5-HT release into lumbar extracellular fluid as measured by in vivo dialysis. 5-HTP significantly increased the amplitude of the MSR and significantly increased the amount of 5-HT in dialysate samples suggesting that 5-HTP enhances the lumbar MSR amplitude by increasing 5-HT release.

5-Hydroxytryptophan↗

PubMed1989

Monoamine-containing fiber plexuses in the spinal cord of guinea pigs during paralysis, recovery and relapse stages of chronic relapsing experimental allergic encephalomyelitis.

Immunohistochemical techniques were used to examine the morphology and distribution of monoamine- and substance P-containing fibers in the spinal cords of guinea pigs in acute paralytic, remission and relapse stages of chronic relapsing experimental allergic encephalomyelitis. During the initial paralytic attack, focal regions of axonal distortion appeared in the white matter of the cervical and thoracic cord; and axon terminal depletion in the gray matter of the caudal spinal cord was pronounced. This neuropathology persisted throughout remission and was exacerbated during relapse of paralysis. These results suggest that axonal damage is an important component of the pathophysiology of this autoimmune disease.

Animals↗

PubMed1989

Thyrotropin-releasing hormone (TRH) effects on spinal cord neuronal excitability.

TRH is found in terminals in the dorsal, lateral, and ventral horns of the spinal cord and apparently has at least a weak facilitatory effect on excitability of neurons in all these locations. These findings suggest that TRH may facilitate transmission in somatosensory pathways, enhance sympathetic outflow from the spinal cord, and facilitate somatic motoneuron excitability, at least transiently. All studies that have examined TRH effects on spinal neuronal excitability have used exogenously administered TRH. Virtually nothing is known about how spinal neuronal functioning might be affected by TRH released from terminals after activation of TRH-containing cell bodies. The acquisition of this knowledge awaits the development of specific TRH antagonists. Preliminary experiments suggest that TRH may have prolonged facilitatory effects on the excitability of developing or damaged spinal cord neurons. Further studies are necessary to determine how TRH interacts with other neuroactive peptides and monoamines to affect excitability of neurons in the developing, damaged, and normal adult spinal cord.

Animals↗