Biomedical subjects

Yu-Ming Kang

Publications and source records attributed to Yu-Ming Kang.

8 recordsLinked to original sources

PubMed2006

11beta-hydroxysteroid dehydrogenase type 2 activity in hypothalamic paraventricular nucleus modulates sympathetic excitation.

Aldosterone stimulates the sympathetic nervous system by binding to a select population of brain mineralocorticoid receptors (MR). These MR have an equal affinity for corticosterone that is present in substantially higher concentrations, but are held in reserve for aldosterone by activity of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2), which converts corticosterone to an inactive metabolite. Thus, colocalization of MR and 11beta-HSD-2 activity may help identify brain regions that mediate the effects of aldosterone. The present studies tested the hypothesis that 11beta-HSD-2 activity regulates MR-mediated responses in the paraventricular nucleus (PVN) of the hypothalamus, a forebrain region implicated in sympathetic regulation. Real-time-polymerase chain reaction revealed the presence of 11beta-HSD-2 mRNA in PVN. In anesthetized adult male Sprague-Dawley rats, microinjection of the 11beta-HSD-2 inhibitor carbenoxolone (CBX) into PVN increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. Intracerebroventricular injections of CBX excited PVN neurons and increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. The ability of CBX to increase sympathetic activity by inhibiting 11beta-HSD-2, thereby permitting corticosterone to activate MR, was confirmed by the following: Intracerebroventricular glycyrrhizic acid, another 11beta-HSD-2 inhibitor, mimicked the sympathoexcitatory effects of CBX; the sympathoexcitatory effects of CBX were blocked by spironolactone, a MR antagonist. Neither CBX nor glycyrrhizic acid elicited a response in adrenalectomized rats. These findings suggest that MR in PVN contribute to sympathetic regulation and may be activated by aldosterone or corticosterone (or cortisol in humans) depending on the state of 11beta-HSD-2 activity.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2006

Paraspinal muscle spindle responses to the duration of a spinal manipulation under force control.

OBJECTIVE: More than 90% of chiropractic patients receive high-velocity, low-amplitude spinal manipulation (HVLA-SM) as part of their chiropractic care. The purpose of the current study was determine how the duration of a lumbar HVLA-SM given under force control affects the discharge of paraspinal muscle spindle afferents. METHODS: Experiments were performed on deeply anesthetized adult cats treated in accordance with the Guiding Principles in the Care and Use of Animals approved by the American Physiological Society. Muscle spindle afferents were identified in the dorsal roots. Neural activity was recorded from individual spindles located in the low back predominately from multifidus and longissimus muscles. Spinal manipulative loads were applied to the L6 vertebra. Force-time profiles were half-sine waves with impulse durations of 25, 50, 100, 200, 400, and 800 milliseconds, delivered at constant magnitudes of 33%, 66%, or 100% body weight. The relationships between spinal manipulation duration and muscle spindle responses were determined using a randomized block design. RESULTS: Mean instantaneous discharge frequency increased with decreasing impulse duration. There appeared to be a threshold effect for impulse duration below which the increase in muscle spindle discharge changed greatly with decreasing impulse duration and above which the discharge did not substantially change with decreasing impulse duration. This threshold was in the vicinity of the duration of an HVLA-SM applied clinically (<or=200 milliseconds). After the manipulation, muscle spindle afferents often became silent, but manipulation duration had little effect on this duration and also had little effect on the time it took for the afferents to recover their initial resting discharge. CONCLUSIONS: The findings suggest that one biomechanical characteristic of an HVLA-SM is its capacity to load paraspinal muscle spindles at a rate where their velocity sensitivity predominates over their length sensitivity.

Animals↗

PubMed2005

Effect of spinal manipulation duration on low threshold mechanoreceptors in lumbar paraspinal muscles: a preliminary report.

STUDY DESIGN: Electrophysiologic recordings were obtained from low threshold primary afferent neurons innervating lumbar multifidus and longissimus muscles in the anesthetized cat. OBJECTIVE: The purpose of this study was to classify sensory nerve endings in lumbar paraspinal muscles and characterize their responses to biomechanical loads applied over a range of durations that encompass those occurring during spinal manipulation. SUMMARY OF BACKGROUND DATA: Neural responses arising from the mechanical input during spinal manipulation are thought to contribute to this maneuver's therapeutic effects. Because manual therapies are distinguished to a large extent on the basis of the speed with which they are applied, it is important to understand how their rate of application affects the signaling properties of primary afferent neurons innervating paraspinal tissues. If alterations in sensory input do contribute to the mechanism of spinal manipulation's therapeutic effect, it seems reasonable to expect that these primary afferents would respond to spinal manipulation in some unique fashion. METHODS: Experiments were performed on 6 adult cats. A L4-L5 laminectomy was performed and the L6 dorsal roots exposed. The L6-L7 vertebrae and associated paraspinal tissues remained intact bilaterally, including lumbodorsal fascia, multifidus, longissimus, iliocostalis muscles, and deeper tissues. Forceps were clamped tightly onto the lateral surfaces of the L6 spinous process through a thin narrow, slit in the lumbodorsal fascia. Single unit afferent activity was recorded from fine filaments teased from the L6 dorsal root. Instantaneous discharge frequency was calculated. Afferents were classified based on von Frey threshold, conduction velocity, and responses to direct muscle stimulation and to succinylcholine injection. Spinal manipulative-like loads were applied to the L6 vertebra (posterior to anterior) using a programmable electronic feedback control system. Force-time profiles were half-sine waves with durations of 25, 50, 100, 200, 400, and 800 milliseconds delivered at constant magnitudes of 33%, 66%, or 100% body weight. RESULTS: The 6 afferents were classified as low threshold mechanoreceptors based on von Frey thresholds being less than 6 g. Five afferents were Group I or II muscle proprioceptors and one afferent was a Group III muscle mechanoreceptor. The receptive field for 2 of the 6 afferents was in the multifidus muscle and the receptive field of the remaining 4 afferents was in the longissimus muscle. In general, the mean instantaneous discharge frequency for all 6 afferents increased abruptly as the duration of the impulse approached 100 milliseconds. An increase in loading magnitude (33% vs. 66% vs. 100% body weight) did not appear to systematically affect the discharge from the 6 low threshold mechanoreceptors. CONCLUSIONS: This preliminary report suggests that abrupt changes in neural discharge (instantaneous frequency) of low threshold muscle mechanoreceptors of the lumbar spine occur as the duration of a biomechanical load approaches that typically used during spinal manipulation. These changes could comprise part of the mechanism contributing to this intervention's physiologic effects. Further studies are warranted to better understand the signaling properties of a wider range of sensory receptors as well as determine the central effects of these high frequency discharges.

Anesthesia↗

PubMed2004

Serotonin modulates hypothalamic neuronal activity.

Effects of serotonin (5-HT) on electrophysiological activities of single hypothalamic arcuate neurons in rat brain slices were observed by extracellular recording. The results showed that (1) of 385 arcuate neurons observed, the patterns of spontaneous firing were divided into 3 categories: "slow irregular" (46.0%), "fast continuous" (22.6%), and "bursting" firing (31.4%); (2) of 149 neurons tested for 5-HT, most (55.0%) responded to the drug by decreasing firing rate, 22.2% by increasing firing rate, 11.4% exhibit biphasic pattern, and 11.4% did not respond to 5-HT application; (3) substitution of low Ca2-high Mg2+ artificial cerebrospinal fluid (ACSF) for normal ACSF did not abolish the 5-HT-induced excitatory effect while it did abolish the 5-HT-induced inhibitory effect, suggesting the effect in latter cases was elicited by a Ca2+-dependent release of neuroactive substances; (4) cyproheptadine, a non-selective 5-HT receptor antagonist, antagonized the 5-HT-induced excitatory effect in all neurons tested, while pindolol, a 5-HT1A/1B receptor antagonist, antagonized the 5-HT-induced excitatory effect in 50% of neurons tested; (5) both cyproheptadine and pindolol antagonized the 5-HT-induced inhibitory effect; and (6) bicuculline, a GABAA receptor antagonist, antagonized the 5-HT-induced inhibitory effect. These results suggest that 5-HT may exert its excitatory effects directly through 5-HT1A/1B and other subtypes of 5-HT-receptors located on the surface of the neurons recorded, while its inhibitory effects are mediated indirectly through the activation of a local inhibitory GABAergic interneuron.

Action Potentials↗

PubMed2004

Sensitization of mechanosensitive gastric vagal afferent fibers in the rat by thermal and chemical stimuli and gastric ulcers.

In the present study we examined the effects of acute thermal and chemical stimuli and gastric ulceration on mechanosensitive gastric vagal afferent fibers. Single-fiber recordings were made from the cervical vagus nerve. Mechanosensitive afferent fibers were identified by response to gastric distension (GD). Intragastric pressure was maintained below 3 mmHg during intragastric instillation of saline, heated saline, HCl, or glycocholic acid. Responses to graded GD (5-60 mmHg, 20 s, 4-min interval) were determined before and after 30-min exposure to thermal or chemical stimuli. All mechanosensitive fibers studied were C-fibers (mean CV: 1.07 +/- 0.07 m/s). Saline (37 degrees C) did not affect resting activity or alter responses to GD, but exposure to heated saline (46 degrees C) significantly increased resting activity and sensitized responses to GD. The decrease in resting activity was hydrochloric acid concentration dependent (0.025-0.2 N), but responses to GD were sensitized after 30-min exposure to 0.1 N HCl (n = 7). The bile acid glycocholic acid significantly increased resting activity and desensitized responses to GD at an intragastric pH of 7, and similarly increased resting activity but sensitized responses to GD (n = 6) at an intragastric pH of 1.2. Vagal afferents recorded in rats with gastric ulcers had significantly greater resting activity and responses to GD than sham ulcer rats; intragastric instillation of glycocholic acid (pH 1.2) further increased afferent fiber excitability. These findings indicate that acute gastric thermal and chemical stimuli alter the response characteristics of mechanosensitive vagal afferents in the absence of inflammation or structural damage. Accordingly, acute sensitization of gastric afferents through different stimulus modalities may contribute to the development of dyspeptic symptoms. In the presence of gastric inflammation, mechanosensitive vagal afferents exhibit a further increase in excitability.

Animals↗

PubMed2003

Gastric inflammation triggers hypersensitivity to acid in awake rats.

BACKGROUND & AIMS: Changes in visceral sensation contribute to the development of dyspepsia. Nonhuman models have previously focused on responses to mechanical stimulation. We studied the response to acid stimulation in the normal and inflamed stomach in rats. METHODS: A balloon and gastrostomy catheter were implanted into the stomach. Electromyographic responses to gastric balloon distention or acid administration through the gastrostomy were recorded from the acromiotrapezius muscle. To characterize chemonociceptive pathways, 0.75 mL HCl (0.05-0.3 N) or saline were given intragastrically in controls and animals after vagotomy, splanchnic nerve resection, or chemical denervation with capsaicin. The effect of inflammation was examined after induction of mild diffuse gastritis using iodoacetamide or creating gastric ulcers by injecting 60% acetic acid for 45 seconds into a clamped area of the stomach. RESULTS: Visceromotor electromyographic responses increased within 2 minutes after HCl administration (0.15 and 0.3 mol/L) but not saline or lower acid concentrations. Vagotomy and pretreatment with capsaicin but not splanchnic nerve resection abolished this response. Prior acid administration did not acutely sensitize animals to subsequent gastric distention. Gastritis and gastric ulcers enhanced the visceromotor responses to intragastric acid. CONCLUSIONS: In awake rats, visceromotor responses to intragastric acid are quantifiable, reliable, and reproducible. Aversive responses to acute noxious chemical stimuli primarily require vagal but not spinal sensory pathways. Injury-induced sensitization to intragastric acid administration is consistent with a potential role of chemical stimulation in triggering dyspeptic symptoms.

Animals↗

PubMed2002

Serotonin excites arcuate neurons directly but inhibits them through intercalated GABAergic neurons.

Effects of serotonin (5-HT) on spontaneous discharges of single hypothalamic arcuate neurons were observed in rat brain slices by extracellular recordings. The results showed that (1) of 149 neurons selected randomly and tested for 5-HT application, 33 (22.2%) were excited, 82 (55.0%) were inhibited, and 34 (22.8%) showed biphasic responses or failed to respond; (2) substitution of low Ca(2+)-high Mg(2+) artificial cerebrospinal fluid (aCSF) for normal aCSF abolished the 5-HT-induced inhibitory effect but failed to affect the 5-HT-induced excitatory effect; (3) cyproheptadine, a non-selective 5-HT receptor antagonist, could block either the 5-HT-induced excitatory or inhibitory effects in all neurons tested; and (4) bicuculline, a GABA(A)-receptor antagonist, blocked the 5-HT-induced inhibitory effect. These results imply (1) 5-HT excites arcuate neurons through a mechanism that is insensitive to the decreased extracellular Ca(2+), suggesting a direct postsynaptic action of 5-HT on the 5-HT-receptors located in the membrane of the neurons recorded; and (2) 5-HT might elicit the inhibitory effect through a Ca(2+)-sensitive release of GABA from intercalated GABAergic local neurons that are excited first by 5-HT.

Animals↗

PubMed2002

Electrophysiologic evidence for an intersegmental reflex pathway between lumbar paraspinal tissues.

STUDY DESIGN: Electrophysiologic recordings were obtained from a lumbar paraspinal nerve or muscle in the anesthetized cat while electrically stimulating a paraspinal nerve or facet capsule in an adjacent lumbar segment. A variety of approaches were used to demonstrate the reflex nature of both the nerve and the muscle response. OBJECTIVE: The primary purpose of this study was to seek electrophysiologic evidence for the presence of intersegmental reflexes between adjacent lumbar vertebral segments. A second purpose of this study was to confirm a previous procedure used to evoke paraspinal reflexes. This previous work had shown that electrical stimulation of the L1-L2 facet joint capsule elicits electromyographic activity from multifidus muscle one to two vertebral segments caudal to the stimulated facet in a porcine preparation. SUMMARY OF BACKGROUND DATA: Biomechanical approaches have stressed the need for spinal stability to avoid conditions that could give rise to low back dysfunction. It seems reasonable to believe that reflex interactions between vertebral segments contribute to the sensorimotor integration of lumbar paraspinal tissues. It also seems reasonable to believe that alterations or abnormal elicitation of these reflexes could contribute to biomechanical changes associated with low back pain and paraspinal muscle spasm. METHODS: Experiments were performed on 23 alpha-chloralose anesthetized adult cats. In eight cats the L3, L4, and L5 medial branch from each dorsal ramus was exposed and placed on a bipolar hook electrode. In six cats the L4 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In three of the six cats the L5 medial branch was stimulated and a compound action potential was recorded from the L3 medial branch. In one cat the L4 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. In one cat the L3 medial branch was stimulated and a compound action potential was recorded from the L5 medial branch. At the end of each protocol the medial branch was cut just proximal to the stimulating electrode to confirm that the compound action potential was reflexive in nature and not initiated by volume conduction. In 15 cats three approaches were used to confirm that multifidus electromyographic activity evoked by electrical stimulation of a lumbar facet capsule was reflexive in nature: 1) by anesthetizing the site of the sensory endings, i.e., the facet capsule, 2) by injecting lidocaine intrathecally to block neural conduction centrally, i.e., within the spinal canal, or 3) by cutting the afferent pathway, i.e., the medial branch of the dorsal ramus. RESULTS: Electrical stimulation of the medial branch of the dorsal ramus innervating the medial-most lumbar paraspinal tissues evoked a compound action potential in the medial branch innervating the medial-most paraspinal tissues one and two segments away. Stimulating voltages between 2 and 70 V were necessary to evoke the compound action potential. Each compound action potential was reflexive in nature because cutting the lumbar medial branch proximal to its contact with the stimulating electrode abolished each compound action potential. The conduction velocity of the reflex ranged from 3.5 to 6.1 m/sec. Electrical stimulation of a lumbar facet capsule evoked lumbar multifidus muscle electromyographic activity. However, injecting lidocaine intrathecally or transecting the medial branch of the dorsal ramus had no effect on electromyographic activity. Injecting lidocaine into the facet or into the multifidus muscle around the facet joint (near the stimulating electrode) significantly decreased the magnitude of the multifidus electromyography. CONCLUSION: These results indicate that afferent impulses conveyed by the medial branch of the dorsal ramus reflexly altered efferent activity to an adjacent lumbar segment. This intersegmental paraspinal reflex may span at least one or two vertebral segments. The data suggest that electrical stimulation of the facet joint capsule may not have reflexly elicited multifidus activity because neither chemical interruption (intrathecal lidocaine) nor physical interruption (nerve transection) of the presumed reflex pathway diminished or abolished the electromyographic response. Volume conduction of the stimulating currents likely elicited multifidus activity during electrical stimulation of the facet capsule. When using electrical stimulation of neural paraspinal tissues to evoke reflex muscle activity, appropriate control experiments must be performed to clearly demonstrate the reflexive nature of the response.

Action Potentials↗