Long-term Follow-up of Cutaneous Hypersensitivity in Rats with a Spinal Cord Contusion

Sometimes, spinal cord injury (SCI) results in various chronic neuropathic pain syndromes that occur diffusely below the level of the injury. It has been reported that behavioral signs of neuropathic pain are expressed in the animal models of contusive SCI. However, the observation period is relatively short considering the natural course of pain in human SCI patients. Therefore, this study was undertaken to examine the time course of mechanical and cold allodynia in the hindpaw after a spinal cord contusion in rats for a long period of time (30 weeks). The hindpaw withdrawal threshold to mechanical stimulation was applied to the plantar surface of the hindpaw, and the withdrawal frequency to the application of acetone was measured before and after a spinal contusion. The spinal cord contusion was produced by dropping a 10 g weight from a 6.25 and 12.5 mm height using a NYU impactor. After the injury, rats showed a decreased withdrawal threshold to von Frey stimulation, indicating the development of mechanical allodynia which persisted for 30 weeks. The withdrawal threshold between the two experimental groups was similar. The response frequencies to acetone increased after the SCI, but they were developed slowly. Cold allodynia persisted for 30 weeks in 12.5 mm group. The sham animals did not show any significant behavioral changes. These results provide behavioral evidence to indicate that the below-level pain was well developed and maintained in the contusion model for a long time, suggesting a model suitable for pain research, especially in the late stage of SCI or for long term effects of analgesic intervention.

The Effect of NK-1 Receptor Antagonist on the Enhanced Response to Bradykinin by Mustard Oil Treatment of the Rat Uterus / 대한산부인과학회잡지

OBJECTIVE: To find out wheather the substance P takes part in the pain mediating system of uterus, and to ascertain the role of substance P in the hypersensitivity of hypogastric nerve to bradykinin during the uterine inflammation. METHODS: The uterus has two sensory innervations, which are the hypogastric nerve and the pelvic nerve. Since the hypogastric nerve is known to show increased sensitivity to bradykinin, a pain mediator, when the uterus is in inflammatory state, the hypogastric nerve recording was done for electrophysiological study of uterine pain-mediating mechanism in female SD rats (200-250 g). NK1 receptor antagonist (L-703,606) was injected through uterine artery before injecting bradykinin while uterus was under inflammation. RESULTS: The NK-1 receptor antagonist (L-703,606) decreased the spontaneous nerve impulse during inflammation, and it also decreased the hypersensitivity of the hypogastric nerve to bradykinin during the uterine inflammation. CONCLUSION: Substance P mediates the pain sense of hypogastric nerve, and it also plays a role in increased sensitivity of hypogastric nerve to bradykinin while uterus is in inflammatory state.

Effects of Norepinephrine on the Mechanoreceptors of the Urinary Bladder in the Cat / 대한마취과학회지

BACKGROUND: Recent findings suggest that a coupling between the somatic and sympathetic nervous system is critical not only for the development but also for the maintenance of pain behavioral changes. However, studies on the effect of sympathetic efferent system on sensory receptors in the visceral organ that is more dependent on the autonomic nervous system are lacking. This study examined whether norepinephrine (NE) had an influence on the mechanoreceptors in the feline urinary bladder. METHODS: Ten adult male cats were used and anesthetized with alpha-chloralose and artificially ventilated. A cannula with the pressure transducer was inserted through the urethra to apply mechanical stimuli and monitor the pressure of bladder. A tiny cannula inserted into the bilateral side branches of vesical arteries were used as a route for a NE (10A.M 9:40 01-10-08 bilaterally) injection. Nerve fiber recordings were obtained from the distal stump of the pelvic nerve. RESULTS: After the NE injection, the response of mechanoreceptors (n = 13) to the isotonic pressure stimulus (50 - 60 mmHg) decreased significantly (p < 0.05) in terms of sensitivity (i.e., ratio of nerve activity change to urinary bladder pressure change). The responses to pressure stimuli after an injection of an alpha1 adrenoceptor blocker (terazosin) reversed the effect of NE. The responses of mechanoreceptors to isotonic pressure stimulus were not affected significantly by NE with preinjection of an alpha2 adrenoceptor blocker (yohimbine). CONCLUSIONS: These results suggest that NE may have influence on the sensitivity of mechanoreceptors in the normal feline urinary bladder via an alpha1 adrenoceptor.

Increased response of hypogastric nerve fibers to bradykinin by mustard oil-induced uterine inflammation in the rat

It is well known that the inflammation of somatic tissues, bladder and colon can alter the sensitivity of primary afferents innervating these tissues. To see if uterine afferents also show altered sensitivity, we examined their responses to the algesic agent bradykinin before and after induction of uterine inflammation. Inflammation was induced by injecting the mustard oil into the uterine lumen of adult female rats. After induction of inflammation, the response latency to bradykinin did not change, but the duration and peak of the response and integrated impulse discharges during the response period increased significantly. Furthermore, after inflammation, the level of resting discharges of the afferents was much higher. These results are consistent with the idea that the inflammation can sensitize the uterine afferents.

Effect of heat shock protein 72 on the generation of reperfusion arrhythmias

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats (n=60, 2.5 ~ 4 kg) were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p<0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

Effects of Exercise on Neuropathic Pain in an Experimental Model of Peripheral Neuropathy

OBJECTIVE: The purpose of this study was to evaluate the short- and long-term effects of exercise on neuropathic pain. METHOD: Pain responses between rats in the exercise and control groups were compared to evaluate the effects of exercise in neuropathic pain. Materials consisted of 30 male Sprague-Dawley rats (8 weeks old, 180~200 g), which were divided into an exercise group (n=15) and a control group (n=15). Neuropathic pain was produced by partially injuring the nerve innervating the tail. Running exercise was given on a Rota-rod treadmill exercise machine for 3 weeks (3.1 Km/day, 6 cycle of 9 minutes exercise and 1 minute rest). Behavioral reactions to mechanical allodynia were checked using a von Frey hairs of 2.0 g (19.6 mN) bending force at 10 minutes, 1 hour and 24 hours post-exercise to evaluate the short term effects of exercise. Behavioral reactions to mechanical and thermal allodynia with 4 degrees C or 40 degrees C were evaluated 7, 14, 21 and 28 days following exercise. RESULT: The exercise group exhibited less tail-flick frequencies to mechanical stimulation from 58.8+/-6.8% to 41.1+/-5.4%, 37.6+/-13.2% at 1 and 24 hours post-exercise compared to the control group, but there was no significant difference between the groups at weeks 1 through 4. In the exercise group, the decrease of tail-flick frequencies were blocked by naloxone (2 mg/kg i.p.). It is suggested that long-lasting muscle exercise (e.g. running) which influences central endorphin mechanisms giving analgetic effects. CONCLUSION: The results of this study support the hypothesis that the exercise can reduce neuropathic pain in the acute stage.

Gradual reperfusion lowers the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia

Blood flow restoration to ischemic zone of the heart is essential to salvage of ischemic tissue. However, there is a large body of evidence documenting that the reperfusion can induce reperfusion injury like reperfusion-induced malignant arrhythmias. In the present study, employing a cat model of regional cardiac ischemia, we examined if reperfusion rendered in a gradual fashion could lower the incidence of reperfusion-induced ventricular fibrillation (VF), which usually precipitated within a few to several tens of seconds after abrupt reperfusion. The experiments were conducted with male mongrel cats (n=46, 2.5-5 kg). The animals in the control and 30 MIN groups were subjected to an episode of 20- and 30-min left anterior descending coronary artery occlusion, respectively, followed by abrupt reperfusion. The animals in 5 G and 10 G groups received gradual reperfusion over a 5- and 10-min period, respectively, following a 20-min occlusion. The proportion of animals that exhibited VF during the reperfusion phase was 11/15 in the control, 7/10 in the 30 MIN, 5/10 in the 5 G and 2/11 in the 10 G groups. The incidence of VF in the 10 G group was significantly lower than that in the control or 30 MIN group subjected to abrupt reperfusion. These results suggest that the gradual reperfusion is a useful procedure against reperfusion-induced VF.

Hypothermic preconditioning lowers the incidence of hypothermic arrest in neonatal rat

This study was performed to examine 1) Whether hypothermic cardiac arrest produces myocardial HSP72 expression; 2) And if, whether it serves to protect the heart against the subsequent hypothermic arrest. In the present study, neonatal rats were placed in an icebath to induce hypothermia. To determine whether hypothermic cardiac arrest produces myocardial HSP72, experimental animals were subjected to 10-min hypothermic insult before the extraction of the heart. The intervals between the insult and extraction were 1 (1 HR), 4 (4 HR), 8 (8 HR), 24 (24 HR) or 72 (72HR) hours. A minimal amount of HSP72 was detected in control, 1 HR and 72 HR groups. In contrast, 8 HR and 24 HR groups showed a significant level of HSP72 expressions. To assess the cardioprotective effect of HSP72 against hypothermic cardiac arrest, we compared the proportion of recovery from the arrest between control and preconditioned (PREC) animals. Control animals were subjected to 20-min hypothermic insult, while PREC group was preconditioned by 10-min hypothermic insult 8 hours before the 20-min test hypothermic insult. Resuscitation rate from cardiac arrest induced by the 20-min hypothermic insult in PREC group was significantly higher than that in controls. These results suggest that the cardioprotective effect of hypothermic preconditioning is associated with an increase in HSP72 expression.

The effect of the occlusion of the left bronchial artery on the production of HSP70 cat lung / 결핵

Several stresses are known to induce synthesis of heat shock protein. The present study was performed to see whether pulmonary ischemia, induced by the bronchial artery occlusion, produced HSP70 in cat lung. To this aim we compared experimental and control groups of cats with respect to the HSP70 production in the lung. Experimental animals were subjected to 10-min bronchial artery occlusion followed by reperfusion. The interval between the end of the occlusion and the end of the reperfusion was 1 hour, 4 hours and 8 hours, whereas control animal was not subjected to any manipulation except anesthesia. According to the interval differences, experimental animals were divided into 1HR, 4HRs and 8HRs groups. To determine the induction of HSP70 in each group, total proteins of lung tissues were extracted and separated by PAGE electrophoresis. Immunoblotting with a mouse monoclonal anti-HSP70 IgG antibody revealed that HSP70 was not detected in the pulmonary tissues resected from control, 1HR or 4HRs groups. In contrast, HSP70 expression in 8HRs group was marked. These results suggest that pulmonary ischemia by the bronchial artery occlusion produces HSP70 in a delayed

Determinant role of the severity of hypoxia in the induction of reoxygenation injury in cat lung

Although reoxygenation is the best way to salvage hypoxic tissues, reduced oxygen species (ROS) generated during reoxygenation are known to cause further tissue injuries and the induction of heat shock proteins (HSPs). The present study was undertaken to determine any causal relationship between the severity of hypoxia and the opposite outcomes, either beneficial or detrimental, of the subsequent reoxygenation by measuring the HSP72. To this aim, one group (6 male cats, 2.5 ~ 3.5 kg) was subjected to a 5-min episode of hypoventilation (H, ventilation rate: 5/min) for the induction of slight hypoxia and the other group (6 male cats, 2.4-3.7 kg) was subjected to a 5-min episode of apnea (A) for severe hypoxia. Each 3 animals from both groups received a 10-min episode of ventilation with 95% O2 (O), whereas the remainder did not. After these procedures, all animals were allowed to be ventilated within physiological range for 1, 4, or 8 hours (1H, 1HO, 4H, 4HO, 8H, 8HO, 1A, 1AO, 4A, 4AO, 8A and 8AO groups). Control animals did not receive any manipulation. The arterial blood pCO2 was significantly higher just after apnea than hypoventilation, while pO2 and pH were significantly lower just after apnea than hypoventilation. Western blot analysis revealed that the magnitude of HSP72 synthesis is larger in 1H, 4H and 8H groups than in 1HO, 4H and 8HO groups, respectively. In contrast, 1AO, 4AO and 8AO groups more induced HSP72 than 1A, 4A and 8A groups, respectively. These results suggest that the reoxygenation is beneficial after slight hypoxia but detrimental after severe hypoxia.

The effects of the uterine pain on the spinal reflex in the cat / 대한산부인과학회잡지

No abstract available.

A study on the neuronal circuit of the utero-muscular reflex / 대한산부인과학회잡지

No abstract available.

Changes in Impulse Discharge of Muscular Afferent Fiber Activated by Lactic Acid / 대한정형외과학회잡지

In anesthetized cats the effects of lactate-activated muscle spindle upon the group Ia muscular afferent fibers were studied. Laminectomy was done from L5 to Sl spinal cord level. Extracellular recording was done at dorsal root to record the impulse discharge from group Ia muscular afferent fibers. 1) Muscle spindle of Gastrocnemius-Soleus muscle were activated by lactate injection and exhibited increased impulse discharge through group Ia muscular afferent fibers. 2) There was latency of 7-12 seconds before muscle spindle is activated by lactate injection. But the whole response was not dose related. 3) The response pattern after lactate injection was divided into three groups which were excitation, inhibition and inhibition with preceding excitation. 4) Some responses were similar to those of bradykinin, sympathetic stimulation (adrenaline injection) and succinylcholine injection. 5) It was suggested that muscle spindle has characteristics of polymodal receptor which has responses to not only mechanical stimulation but also chemical stimulation.

Experimental Injection Injury of the Sciatic Nerve: Part 11 Physiological Study

In clinical practice a serious sciatic nerve injury may result from an errornous injection of commonly used antibiotics and other therapeutic or prophylactic agents into the gluteal region which can occur at any age, especially common in infants, children and small debilitated patients. Although many isolated cases and several large series of injuries have been reported, the pathogenesis, pathology and its physiology of injection injury of the peripheral nerves in man have been poorly studied. This experimental study was conducted in order to observe the changes and degree of the functional disability of the sciatic nerve following injection of various drugs such as Rheumapyrine, Chloromycetin, Penicillin and physiological normal saline solution. Fourty-three normal adult rabbits were divided into four groups depending on injected materials and also divided into two groups of acute and chronic stages. The drugs were injected into the right sciatic nerve intraneurally and around the left sciatic nerve perineurally. For the functional study in the nerve, contractability of the calf muscle was recorded on a physiograph at intervals of 1, 3, 5, 15 and 30 minutes after the injection of the drugs. Rheobase, chronaxie and strength-duration curve of both extensor and flexor muscles of fet were recorded and measured on a chronaxie meter at intervals of 1, 2, 3 and 4 weeks after the injection. The physiogram showed the greatest reduction in contractability of the muscles in Rheumapyrine, moderate reduction in Penicillin and the least reduction in Chloromycetin group. In the measurements of rheobase and chronaxie there were marked increase of values in group of Rheumapyrine injection. There was no significant differences in values among the group of Penicillin, Chloromycetin and saline injections in comparison with those in the control group. In the analysis of strength-duration curve, it showed a pattern of complete denervation in 3 cases and a pattern of partial denervation in 3 out of 8 cases with Rheumapyrine injection, and a pattern of partial denervation in 3 out of 6 cases with Penicillin and 2 out of 8 cases with Chloromycetin injection. There was no significant differences in values of rheobase, chronaxie and strength-duration curve as time elapsed following the injury. It was postulated the functional and physiological disabilities were developed after the injection when there was a severe degree of nerve damages on the basis of histopathological study.