Variations of the prominences of the bony palate and their relationship to complete dentures in Korean skulls.

The osteological and morphological variations of the prominences in the bony palate of 160 Korean skulls were studied. The frequency of the occurrence of the posterior palatine crest, located on the posterior border of the greater palatine foramen, was 13.8%. Palatal ridges were observed commonly in the skulls; however, the smooth type, which has no palatal ridges in the palate, was shown in 14.7% of cases, and palatal spines were observed in 33.8%. The prevalence of palatal tubercles was 11.6%, and all were found in the molar region. The palatine torus was found in 18.8% of cases and the most common type was along the median palatine suture from the incisive foramen to the posterior border of the palatine bone (63.3%). No significant differences between sexes or sides were found in the posterior palatine crest, palatal ridges, and palatal tubercle. However, the sex distribution of the palatine torus was significantly different (P < 0.05). These results would be helpful clinically in fabricating maxillary complete dentures for edentulous patients.

Anatomical study of the pyramidal process of the palatine bone in relation to implant placement in the posterior maxilla.

The placement of dental implants in the molar region of the maxilla is often difficult because of insufficient bone volume and the inferior bone quality. In order to avoid these limitations, the pillar of bone, which is composed of the maxillary tuberosity, the pyramidal process of the palatine bone and the pterygoid process of the sphenoid bone, was introduced for implant placement. In fact, the pyramidal process is the posterior structure where implants are placed but until now, there is no available data of the size or shape of the pyramidal process. Therefore, we measured the height, anteroposterior distance and mediolateral distance of the pyramidal process and observed the shape of lateral and posterior surfaces of the pyramidal process of 54 Korean edentulous dry skulls in this study. The height was 13.1 mm (male: 13.6 mm, female: 12.4 mm). The anteroposterior distance was 6.5 mm (male: 6.7 mm, female: 6.1 mm). The mediolateral distance was 9.5 mm (male: 9.9 mm, female: 9.0 mm). The most common type was the right-angled triangle in the lateral surface (44.4%) and in the posterior surface (66.7%). There was no statistical significance between the male and the female in all items (P > 0.05). These results provide anatomical features in relation to placement of dental implants in the molar region of the maxilla and would be useful in treatment planning of partially or completely edentulous patients.

Differential antinociceptive effect of transcutaneous electrical stimulation on pain behavior sensitive or insensitive to phentolamine in neuropathic rats.

The effects of transcutaneous electrical stimulation and systemic injection of phentolamine, a non-specific alpha-adrenergic antagonist, on the behavioral signs of mechanical allodynia and cold hyperalgesia in rats with nerve injury were investigated. Mechanical allodynia and cold hyperalgesia were evaluated by measuring the paw withdrawal frequency (PWF) resulting from repetitive application of a von Frey hair and the paw lift duration (PLD) at a cold temperature, respectively. After a unilateral nerve injury, both PWF and PLD increased in the injured hind paw. Application of low-frequency, high-intensity transcutaneous electrical stimulation (LFHI-TES) to the injured hind paw depressed the injury-induced increased PWF, whereas it had no effect on the injury-induced increased PLD. Naloxone reversed the LFHI-TES produced depression of PWF. Intraperitoneal administration of phentolamine depressed the injury-induced increased PLD without affecting the injury-induced increased PWF. Our results suggest that LFHI-TES, which activates the endogenous opioid systems, produces an antinociceptive effect that appears to be related to whether or not the pain is mediated by sympathetic activity.

Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats.

We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.

The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery.

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.

Involvement of alpha2-adrenoceptors in mediating sympathetic excitation of injured dorsal root ganglion neurons in rats with spinal nerve ligation.

The present study examined the effects of sympathetic stimulation on the activity of primary afferent neurons that had peripheral axons being injured previously by a spinal nerve ligation. About 22% of afferents with injured fibers that showed spontaneous discharge were excited by sympathetic stimulation or systemic injection of adrenaline. Most sympathetically-excited afferent neurons had axons that conducted in the A-fiber range. This sympathetically-evoked afferent excitation was not affected by cutting the spinal nerve at a place close to the dorsal root ganglion (DRG). Yohimbine, alpha2-antagonist, suppressed sympathetically-evoked afferent excitation which was not affected by alpha1-antagonist prazosin. Clonidine, alpha2-agonist, exerted an excitatory effect, whereas alpha1-agonist phenylephrine had no effect on the activity of afferents with injured fibers. No afferent fibers in control preparations responded to sympathetic stimulation. The results suggest that after a spinal nerve ligation, injured DRG neurons with fast-conducting fibers become sensitive to sympathetic activity via activation of alpha2-adrenoceptors.

N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists differentially suppress dorsal horn neuron responses to mechanical stimuli in rats with peripheral nerve injury.

The effects of iontophoretically ejected glutamate receptor antagonists on mechanically evoked responsiveness were examined on wide dynamic range (WDR) dorsal horn neurons in anesthetized rats that received a unilateral ligation of the L5 and L6 spinal nerves 10-15 days previously. Both brush- and pinch-evoked responses of dorsal horn neurons on the nerve-injured side were enhanced. N-Methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5), preferentially suppressed the enhanced pinch-evoked response, whereas (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor selective antagonist, 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX), preferentially attenuated the enhanced brush-evoked response. The results indicate that the enhanced responses to noxious and non-noxious peripheral inputs induced in WDR dorsal horn neurons following the nerve injury are mediated by activation of NMDA and AMPA receptors, respectively.

Effects of iontophoretically applied naloxone, picrotoxin and strychnine on dorsal horn neuron activities treated with high frequency conditioning stimulation in cats.

Transcutaneous electrical nerve stimulation(TENS), acupuncture-needling, and electroacupuncture are useful non-ablative methods in medical practice for relief of pain. These procedures appear to work by causing an increased discharge in afferent nerve fibers which in turn modifies the transmission of impulses in pain pathways. It is known that the mechanism of analagesic effect via these maneuvers are variable depending on the stimulating parameters. For example, the endogenous opioid system is profoundly related to the mechanism when a peripheral nerve stimulation is applied with parameters of low frequency and high intensity. However, when stimulated with parameters of high frequency and high intensity, the reduced activity of dorsal horn neurons is only slightly reversed by a systemic administration of naloxone, a specific opiate antagonist. Thus, the present study was performed to investigate the neurotransmitter that concerns the mechanism of peripheral nerve stimulation with parameters of high frequency and high intensity. We used an iontophoretic application of antagonists of possible related neurotransmitters. The dorsal horn neuron activity which was evoked by squeezing the peripheral cutaneous receptive field, was recorded as an index of pain with a microelectrode at the lumbo-sacral spinal cord. Naloxone, picrotoxin and strychnine were applied at 200nA during a period of conditioning nerve stimulation. We observed the effects of these drugs on the change of dorsal horn neuron activities. The main results of the experiment can be summarized as follows. The spontaneous activity of dorsal horn neurons increased in the presence of glutamate and decreased with GABA. It did not change with naloxone, picrotoxin or strychnine. When naloxone was applied iontophoretically during peripheral nerve stimulation, there was no statistically significant analgesic effect compared with that of the control group. When picrotoxin was applied iontophoretically during peripheral nerve stimulation, the analgesic effect was reduced. When strychnine was applied, the analgesic effect was reduced but did not show a statistically significant difference with the control group. These results suggested that the GABAergic system may have been partially related in the analgesic action of peripheral nerve stimulation with parameters of high frequency and high intensity.

Mechanism of transmission and modulation of renal pain in cats; effect of nucleus raphe magnus stimulation on renal pain.

Initially, when periaqueductal gray (PAG) is electrically stimulated, analgesia is induced, and this phenomenon is called stimulation-produced analgesia. Nucleus raphe magnus (NRM) as well as PAG are known to be the potent analgesic centers. NRM could modulate the nociceptive response of spinal cord neurons through spinally projecting fibers. However, as well as the above analgesic effects have been confined to the somatic pain, it was variable according to species, and the analgesic effect by NRM stimulation on the visceral pain was not yet clarified. In this study the analgesic effect by NRM stimulation on the visceral pain was examined through recording the activities of the dorsal horn neurons with renal input and renal pain, as a type of visceral pain. The renal pain was induced by ureteral occlusion or renal arterial occlusion, which in turn activated the renal mechanoreceptor or chemoreceptor. These cells had concomitant somatic input. In order to compare the effects of NRM stimulation on the renal pain with somatic pain, the somatic stimulation such as squeezing was conducted on the peripheral receptive field. The main results are summarized as follows: 1) After an electrical stimulation of NRM, spontaneous activities of dorsal horn neurons with renal input were reduced to 73.3 +/- 9.7% of the control value. 2) After an electrical stimulation of NRM, activities of dorsal horn neurons with renal input evoked by a brush, a type of non-noxious stimuli, did not change significantly. But the activities by a squeeze, a type of noxious stimuli, the activities were reduced to 63.2 +/- 7.2% of the control value. 3) After an electrical stimulation of NRM, activities of dorsal horn neurons with renal input evoked by occlusion of ureter or renal artery were reduced to 46.7 +/- 8.8% and 49.0 +/- 8.0% of the control value respectively. 4) The inhibitory effect of NRM on the dorsal horn neurons with renal input did not show any difference between renal A delta fiber and C fiber group. 5) By the electrical stimulation of NRM, the activities evoked by ureteral occlusion showed more reduction in the high threshold cell group than in the wide dynamic range cell group. These results suggest that activation of NRM can alleviate the renal pain as well as the somatic pain by modulating the dorsal horn neurons activities.

Electrophysiological evidence for the antinociceptive effect of transcutaneous electrical stimulation on mechanically evoked responsiveness of dorsal horn neurons in neuropathic rats.

Using a rat model of peripheral neuropathy induced by a tight ligation of L5-6 spinal nerves, the effects of transcutaneous electrical stimulation on the mechanical responses of wide dynamic range (WDR) dorsal horn neurons were investigated. The responses of the WDR neurons to both the brush and pinch stimuli were found to be enhanced in the neuropathic rats compared to those in the normal rats. These enhanced responses were depressed by low-frequency and high-intensity transcutaneous electrical stimulation (2 Hz, 4-5 mA) applied to the somatic receptive field. The durations of the depressive effects on the brush responses ranged between 30 and 45 min and those on the pinch responses were 60-90 min. These results imply that the transcutaneous electrical stimulation used here produces an antinociceptive effect via a depressive action on the enhanced mechanical responsiveness of the spinal neurons in this rat model of peripheral neuropathy.

Intracellular acidosis decreases the outward Na(+)-Ca2+ exchange current in guinea pig ventricular myocytes.

The Na(+)-Ca2+ exchange transport operating in outward mode has been suggested to cause Ca2+ entry during reperfusion or reoxygenation, exchanging extracellular Ca2+ for intracellular Na+ that has accumulated during ischemia or cardioplegia. During cardioplegia, however, an increase in Ca2+ entry via this mechanism can be decreased due to increased intracellular H+ activity and a decrease in cellular ATP content. In this study giant excised cardiac sarcolemmal membrane patch clamp technique was employed to investigate the effect of cytosolic pH change on the Na(+)-Ca2+ exchanger, excluding the effect of ATP, in guinea pig cardiac myocytes. The outward Na(+)-dependent current, which has a characteristics of Hill equation, was decreased as pH was decreased in the range of 7.5-6.5. The current density generated by the Na(+)-Ca2+ exchange transport was 56.6 +/- 4.4 pA/pF (Mean +/- S.E.M.) at pH 7.2 and decreased to 42.9 +/- 3.0 pA/pF at pH 6.9. These results imply that Na(+)-Ca2+ exchange transport, operating in a reverse mode during cardioplegia, decreases due to increased intracellular H+, and further suggest that consequent intracellular Na+ accumulation is one of aggravating factors for Ca2+ influx during reoxygenation or reperfusion.

Mechanism of transmission and modulation of renal pain in cats; effects of transcutaneous electrical nerve stimulation on renal pain.

Transcutaneous electrical nerve stimulation (TENS) has widely been employed as a method of obtaining analgesia in medical practice. The mechanisms of pain relief by TENS are known to be associated with the spinal gate control mechanism or descending pain inhibitory system. However, most of the studies concerning the analgesic effects and their mechanisms for TENS have dealt with somatic pain. Thus, in this experiment, we investigated the analgesic effects of TENS on renal pain as a model of visceral pain, and the characteristics of the dorsal horn cells with renal inputs. The renal pain was induced by acute occlusion of the ureter or renal artery. The main results are summarized as follows: 1) The renal nerve was composed of A beta, A delta and C fiber groups; the thresholds for each group were 400-800 mV, 1.1-1.5 V, and 2.1-5.8 V, respectively. 2) The dorsal horn cells tested received A and/or C afferent fibers from the kidney, and the more C inputs the dorsal horn cells had, the greater was the response to the stimuli that elicited the renal pain. 3) 94.9% of cells with renal input had the concomitant somatic receptive fields on the skin; the high threshold (HT) and wide dynamic range (WDR) cells exhibited a greater responses than low threshold (LT) cells to the renal pain-producing stimuli. 4) TENS reduced the C-responses of dorsal horn cells to 38.9 +/- 8.4% of the control value and the effect lasted for 10 min after the cessation of TENS. 5) By TENS, the responses evoked by acute occlusion of the ureter or renal artery were reduced to 37.5 +/- 9.7% and 46.3 +/- 8.9% of the control value, respectively. This analgesic effects lasted 10 min after TENS. 6) The responses elicited by squeezing the receptive fields of the skin were reduced to 40.7 +/- 7.9% of the control value and the effects lasted 15 min after TENS. These results suggest that most of dorsal horn cells with renal inputs have the concomitant somatic inputs and TENS can alleviate the renal pain as well as somatic pain.

Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons.

The responses of 144 spinothalamic tract (STT) cells were recorded in 15 anesthetized macaque monkeys (Macaca fascicularis). Three to 4 weeks prior to the acute experiment, the sciatic nerve was surgically exposed on one or both sides so that capsaicin or vehicle could be applied. Responses of STT cells recorded in 3 experimental groups were compared: untreated (21 cells), vehicle-treated (40 cells), and capsaicin-treated (83 cells). The background activity of cells in the vehicle- and capsaicin-treated groups was the same as in the untreated group (that is, cells on the side contralateral to surgery). Responses to innocuous (BRUSH) and noxious (PINCH) mechanical stimuli were unchanged by vehicle or by capsaicin treatment. However, responses to other noxious (PRESSURE and SQUEEZE) mechanical stimuli were significantly increased in the vehicle-treated group. Compared with a large reference population, all experimental groups showed a significant increase in overall responsiveness to mechanical stimuli (as determined by cluster analysis), greatest in the vehicle-treated group. Responses to noxious heat stimuli were significantly reduced in the capsaicin-treated group for 45 degrees C and 47 degrees C stimuli. Volleys in A fibers, probably A delta fibers, evoked prolonged responses in many STT cells of all treatment groups. Electron microscopic counts of axons in the sciatic nerves of animals treated with capsaicin showed a reduced number of C fibers but no appreciable loss of myelinated axons. This loss of unmyelinated sensory fibers was presumably responsible for the reduction in the responses of the STT cells to noxious heat stimuli. Increased responses to some noxious mechanical stimuli and to A fiber volleys may have been the consequence of several factors, including surgical manipulation, a chemical action of vehicle and a contralateral action of capsaicin treatment.

Compartmental analysis of RBC circulation through the rabbit kidney.

This experiment involved 12 rabbits of both sexes, weighing 2.1 kg. After anesthesia, the kidneys were exposed, isolated and cannulated in the renal artery, ureter and sometimes in the vein as well. The kidney were perfused through the renal artery with Krebs-Henseleit solution, which were then filtered to be free of particles, gased with 95% O2-5% CO2, and kept at 37 degrees C. We measured RBCs concentrations by means of Coulter Counter in the venous outflow collected, and plotted them against the volume perfused. Using 2 different flow rates, 9 ml/min (group I) and 19 ml/min (group II), we found that the RBCs decreased in a multiexponential decay fashion and a biophysical model for each flow rate was constructed. These models indicated that there were more cell stores (2.20 x 10(10)) in the fast compartment of group II than in group I (1.72 x 10(10)). This difference is not statistically significant, but certainly coincides with urine flow collected from ureter cannula during perfusion. Our present data clearly suggest that in order to clear 99% blood cells out of 10-12 gm rabbit kidneys, at least 3-6 ml of cell free perfusate is required while clearing the whole blood cells out of human kidneys (200-240 gm) may need 600 ml or more. Thus, we recommend that at least 600 ml of perfusate should be used to clear most of the blood cells in the renal vasculature before renal transplantation is performed.

Effect of peripheral nerve stimulation on the dorsal horn cell activity in cats with cutaneous inflammation.

There are some reports showing that an experience of long-enduring pain causes a change in the pain transmission system, suggesting a plastic nature of the nociceptive system. However, most of the studies concerning the analgesic effect of peripheral nerve stimulation dealt with normal animal or human subjects. So, the present study was undertaken to investigate the effect of peripheral nerve stimulation on the dorsal horn cell activity using a tonic pain model, which was made by producing a cutaneous inflammation. The main results are summarized as follows. 1) The evoked activity by electrical or natural stimulation as well as spontaneous activity was enhanced, and the receptive field size was also expanded by the inflammation. 2) Peripheral nerve conditioning stimulation reduced the C-response of the dorsal horn cell in the normal and inflamed group, and the degree of inhibition between the two groups showed no significant difference. 3) Inhibition of the C-response of the dorsal horn cells by peripheral conditioning stimulation was completely reversed by naloxone in the inflamed group whereas there was a partial block in the normal group.

Different classes of cat spinal neurons display differential sensitivity to sodium pentobarbital.

The effect of graded doses of systemically injected sodium pentobarbital on several classes of spinal neurons was studied using spinal cats. Classes of spinal neurons included unidentified dorsal horn cells, ascending tract dorsal horn cells, and motoneurons. Single unit activity of spinal neurons was evoked by electrically stimulating a peripheral nerve with an intensity strong enough to excite both A and C fibers. The A- and C-fiber evoked activity was compared before and after intravenous injections of small incremental doses of sodium pentobarbital. The activity of different classes of spinal neurons showed different sensitivities to graded doses of systemically injected pentobarbital. The reflex activity of motoneurons elicited by stimulation of peripheral nerve was much more sensitive to pentobarbital than that of dorsal horn cells. In general, activity evoked by peripheral unmyelinated fibers was more susceptible to pentobarbital than was that evoked by myelinated fibers. However, intravenous injections of pentobarbital produced nondifferential suppression of dorsal horn cell activity evoked by noxious and innocuous mechanical stimuli applied to the peripheral receptive fields.

Differential inhibition produced by peripheral conditioning stimulation on noxious mechanical and thermal responses of different classes of spinal neurons in the cat.

The effect of conditioning stimulation of a peripheral nerve on responses of spinal neurons (dorsal horn cells and motoneurons) was studied in 16 decerebrate-spinal cats. The activity of dorsal horn cells was recorded with a microelectrode at the lumbosacral spinal cord and the single-unit activity of motoneurons was recorded from a filament of ventral rootlet divided from either the L7 or S1 ventral root. The responses of spinal neurons were evoked by noxious and innocuous mechanical stimuli and by noxious thermal stimuli applied to the receptive fields. The peripheral conditioning stimulation was applied to the tibial nerve with repetitive electrical pulses (2 Hz) at an intensity either suprathreshold for A delta or C fibers for 5 min. Applying conditioning stimulation to a peripheral nerve produced a powerful inhibition of the responses elicited by noxious stimuli, suggesting this inhibition is an antinociceptive effect. The inhibition produced by peripheral conditioning stimulation was differentially greater on the responses to noxious than to innocuous stimuli. Based on the results obtained from conditioning stimulation with graded strengths, afferent inputs from both myelinated and unmyelinated fibers seem to contribute to the production of the antinociceptive effect. The magnitude of the antinociceptive effect is bigger for the responses to noxious thermal than to mechanical stimuli. Furthermore, the reflex activity recorded in motor axons seemed to be more sensitive than in dorsal horn cells to the antinociceptive effect.

Spinal entry route for ventral root afferent fibers in the cat.

Twelve anesthetized and paralyzed cats were used to study the spinal entry routes of ventral root afferent fibers. In all animals, the spinal cord was transected at two different levels, L5 and S2. The L5 through S2 dorsal roots were cut bilaterally, making spinal cord segments L5-S2 neurally isolated from the body except for the L5-S2 ventral roots. From this preparation, a powerful excitation of the discharge rate of motor neurons and dorsal horn cells within the isolated spinal segments was observed after intraarterial injection of bradykinin (50 micrograms in 0.5 ml saline). This excitation of the spinal neurons can be considered the most convincing evidence of the potential physiologic role of the ventral root afferent fibers entering the spinal cord directly through the ventral root, because the apparent route of neuronal input from the periphery is through the ventral roots. However, additional control experiments conducted in the present study showed that the excitation persisted even after cutting all ventral roots within the isolated spinal segments, indicating that excitation was not mediated by the ventral roots. Furthermore, direct application of bradykinin on the dorsal surface of the spinal cord also increased the motoneuronal discharge rate, suggesting that excitation of spinal neurons produced by intraarterial injection of bradykinin is due to a direct action of bradykinin on the spinal cord. Thus, we provided an alternate explanation for the most convincing evidence indicating that physiologically important ventral root afferent fibers enter the spinal cord directly through the ventral root. Based on existing experimental evidence, it is likely that the majority of physiologically active ventral root afferent fibers travel distally toward the dorsal root ganglion and then enter the spinal cord through the dorsal root.