The present study was designed to investigate the effect of low power GaAsAl laser on Fos expression in the spinal cord induced by noxious mechanical stimulation. Noxious mechanical stimulation was applied to the right hind paw following 30min of low power laser treatment using different intensity and treatment point and the resulting Fos expression in the spinal cord dorsal horn was compared to that obtained in rats exposed only to the noxious mechanical stimulation. The results were summarized as follows: 1. In intact control rats, only a few Fos like immunoreactive(Fos-IR) neurons were evident in the lumbar spinal cord dorsal horn. Similarly, following prolonged inhalation anesthesia, Fos-IR neurons were absent in the dorsal horn of the lumbar spinal cord. In animals treated with noxious mechanical stimulation, neurons with nuclei exhibiting Fos immunostaining were distributied mainly in the medial half of ipsilateral laminae I-V at lumbar segments L3-5. These findings directly indicated that prolonged anesthesia used in this study did not affect the Fos expression in the spinal cord dorsal horn of intact animals and noxious mechanical stimulation treated animals. 2. In acupoint treated animals, 10mW of laser stimulation, not 3mW intensity, significantly reduced the number of Fos immunoreactive neurons in the spinal dorsal horn induced by noxious mechanical stimulation(P<.01). However, the supressive effect of low power laser stimulatin was not observed in 3m Wand 10m W of laser stimulation into non-acupoint. These data indicate that 10mW of low power laser stimulation into acupoint is capable of inhibiting the expression of Fos in the dorsal horn induced by noxious mechanical stimulation. In conclusion, these findings raise the possibility that low power laser stimulation into acupoint may be a promising alternative medicine therapy for the mechanical stimulation induced pain in the clinical field.
The purpose of this study was to investigate the analgesic effect of eugenol, capsaicin and demethoxy-NE. Young adult cats, weighing 2.0 to 3.0kg, were used. Each animal was anesthetized (${\alpha}$-chloralose 60mg per kg body weight) and divided into four groups; control, eugenol, capsaicin and demethoxy-NE group. The anterior digastric muscles were exposed and a pair of electrodes was inserted to record the electromyograms. To expose the pulp, each canine teeth was prepared with a low speed bur under cooling and used for recording anterior digastric muscular EMGs evoked by noxious stimulation of dental pulp. To observe effects on jaw opening reflex, inferior alveolar nerve of both sides were exposed for drug application and wire electrodes were inserted in anterior digstric muscle for recording the EMGs. To observe effects on action potential, saphenous nerves of both sides were exposed and three tissue pools were made from surrounding tissue. The most distal pool was used for applying stimulation, the most proximal one for recording of action potential, and the other one for drug application. One side of inferior alveolar nerve and saphenous nerve were used for eugenol, capsaicin, or demethoxy-NE application, the other side of nerve for control experiments(only vehicle application). Anterior digastric muscular EMGs evoked by noxious stimulation of dental pulp were recorded before drug application, immediate after drug application, at 60 and 120 minutes, and 5 days after drug application. Action potentials were recorded before drug application, immediate after 30 minutes drug application, at 30, 60 and 120 minutes after drug had been washed out. The results were as follows; 1. Eugenol had a continuous blocking effect on the anterior digastric muscular EMGs evoked by noxious pulp stimulation and after 5 days, showed completely blocking effect. 2. After 5 days, demethoxy-NE applied to dental pulp had a considerable blocking effect on the jaw opening retlex evoked by noxious stimulation but capsaicin had no significant effect. 3. After 5 days, eugenol group showed the strongest blocking effect among the all experimental groups on the jaw opening reflex evoked by noxious stimulation of dental pulp and capsaicin group showed the weakest blocking effect. 4. Eugenol had a completely blocking effect on the action potential conductivity of peripheral nerve. Capsaicin and demethoxy-NE had the blocking effect on the action potential conductivity of ${\alpha}$-and C-nerve fibers. 5. Capsaicin, demethoxy-NE and eugenol applied to inferior alveolar nerve surppressed the jaw opening reflex evoked by noxious stimulation of dental pulp.
The purpose of present study was to compare the effects of somatostatin (SOM) and morphine (Mor) on the responses of wide dynamic range (WDR) cells to peripheral noxious stimulation. Single neuronal activity was recorded with a carbon-filament electrode at the lumbosacral enlargement of cat spinal cord. After identifying WDR cells, their responses to peripheral noxious mechanical or thermal stimuli were characterized and the effects of SOM and Mor, applied either iontophoretically or intrathecally, were studied. In most cells SOM and Mor suppressed noxious stimulus-evoked WDR neuronal activity, though a few WDR neurons showed no change or were excited by SOM and Mor. Systemically applied naloxone, a non-specific opioid antagonist, always reversed the Mor induced suppression of neuronal activity evoked by noxious mechanical stimuli, but did not always reverse the suppression of neuronal activity elicited by SOM. The suppressive effect of Mor on thermal stimulus-evoked neuronal activity was partially reversed by naloxone, while that of SOM were not reversed at all. The above results suggest that both Mor and SOM exert an inhibitory effect on thermal and mechanical stimulus-evoked WDR neuronal activity in cat spinal dorsal horn, but the mechanisms are dependent upon the functional populations of dorsal horn nociceptive neurons.
Jung, Sung-Jun;Park, Joo-Min;Lee, Jun-Ho;Lee, Ji-Hye;Kim, Sang-Jeong;Kim, Jun
The Korean Journal of Physiology and Pharmacology
/
v.3
no.4
/
pp.365-373
/
1999
Somatostatin (SOM) is one of the major neuropeptides in dorsal root ganglion cells, but its role in spinal nociceptive process has not been well known. In present study we aimed to investigate the effect of SOM on the response of dorsal horn neurons to the various types of peripheral nociceptive stimuli in anesthetized cats. Using carbon-filament microelectrode, the single cell activities of wide dynamic range neurons were recorded from the lumbosacral enlargement after noxious mechanical (squeeze), thermal (radiant heat lamp) and cold (dry ice) stimulation to the receptive field. Sciatic nerve was stimulated electrically to evoke $A\;{\delta}-$ and C-nociceptive responses. SOM analogue, octreotide $(10\;{\mu}g/kg),$ was applied intravenously and the results were compared with those of morphine (2 mg/kg, MOR). Systemic SOM decreased the cellular responses to the noxious heat and the mechanical stimulation, but increased those to the cold stimulation. In the responses to the electric stimuli of sciatic nerve, $A\;{\delta}-nociceptive$ response was increased by SOM, while C-nociceptive response was decreased. On the other hand, MOR inhibited the dorsal horn cell responses to all the noxious stimuli. From the above results, it is concluded that SOM suppresses the transmission of nociceptive heat and mechanical stimuli, especially via C-fiber, while it facilitates those of nociceptive cold stimuli via $A\;{\delta}-fiber$.
The aim of this study was to investigate the effect of low - power laser used in the medical field for various purposes to suppress pain responses evoked by noxious electrical or mechanical stimuli. After both inferior alveolar nerves and the left anterior digastric muscle of cats under general anesthesia were exposed, a recording electrode for the jaw opening reflex was inserted into the anterior digastric muscle. The right inferior alveolar nerve was dissected under a surgical microscope until the response of the functional single nerve could be evoked by the electrical stimulation of the dental pulp or oral mucosa. The electrical stimulus was applied with a rectangular pulse of 10 ms duration for measuring the threshold intensity of a single nerve fiber in the inferior alveolar nerve which responds to stimulation of dental pulp and oral mucosa. Then a pulse of 1 ms duration was applied for determination of conduction velocity. A noxious mechanical stimulus to the oral mucosa was applied by clamping the receptive field with an arterial clamp. The Ga-As diodide laser(wave length, 904 nm ; frequency, 1,000 Hz) was irradiated to the prepared tooth cavity, inferior alveolar nerve and oral mucosa as a pulse wave of 2 mW for 6 minutes. This was followed by a continuous wave of 15 mW for 3 minutes. The action potential of the nerve and EMG of the digastric muscle evoked by the noxious electrical stimulus and nerve response to noxious mechanical stimulus were compared at intervals of before, immediately after, and at 5, 10, 20, 40, 60 minutes after laser irradiation. The results were as follows: The conduction velocity of the intrapulpal $A{\delta}$- nerve fiber recorded from the inferior alveolar nerve before irradiation had a mean value of $6.68{\pm}2.07m/sec$. The laser irradiation did not affect the conduction velocity of the AS - nerve fiber and did not change the threshold intensity or amplitude of the action potential either. The EMG of the digastric muscle evoked by noxious electrical stimulation to the tooth was not changed by the laser irradiation, whether in latency, threshold intensity or amplitude. The laser irradiated to the receptive field of the oral mucosa which was subjected to noxious stimuli did not affect the amplitude of the action potential or the frequency either.
Trigeminal spinal sensory nucleus is a main relay site in transmission of orofacial pain. Glutamate and aspartate playa role in transmission of primary afferents. This experiment was performed to study the role of capsaicin, KR-25018 and shogaol on the release of glutamate and aspartate from trigeminal spinal sensory nucleus. Release of excitatory amino acids(EAAs) was induced by electrical stimulation of oral mucosa with innocuous or noxious stimuli. Capsaicin($10{\mu}M$), KR-25018($10{\mu}M$), shogaol($10{\mu}M$), ruthenium red and capsazapine were added to perfusion solution to observe the changes in EAA release, and glutamate and aspartate were determined by HPLC. Release of glutamate and aspartate from trigeminal sensory nucleus was increased by noxious stimulation of oral mucosa, but innocuous stimulation did not affect on the release of EAA Capsaicin and KR-25018 increased the release of glutamate and aspartate, and effect of KR-25018 on release of EAA was more potent than capsaicin. But shogaol had a weak effect on release of EAA. Effect of capsaicin and KR-25018 was partially blocked by capsaicin antagonists, ruthenium red and capsazepine.
Magnesium ion is known to selectively block the N-methyl-D-aspartate (NMDA)-induced responses and to have anticonvulsive action, neuroprotective effect and antinociceptive action in the behavioral test. In this study, we investigated the effect of $Mg^{2+}$ on the responses of dorsal horn neurons to cutaneous thermal stimulation and graded electrical stimulation of afferent nerves as well as to excitatory amino acids and also elucidated whether the actions of $Ca^{2+}$ and $Mg^{2+}$ are additive or antagonistic. $Mg^{2+}$ suppressed the thermal and C-fiber responses of wide dynamic range (WDR) cell without any effect on the A-fiber responses. When $Mg^{2+}$ was directly applied onto the spinal cord, its inhibitory effect was dependent on the concentration of $Mg^{2+}$ and duration of application. The NMDA- and kainate-induced responses of WDR cell were suppressed by $Mg^{2+}$, the NMDA-induced responses being inhibited more strongly. $Ca^{2+}$ also inhibited the NMDA-induced responses current-dependently. Both inhibitory actions of $Mg^{2+}$ and $Ca^{2+}$ were additive, while $Mg^{2+}$ suppressed the EGTA-induced augmentation of WDR cell responses to NMDA and C-fiber stimulation. Magnesium had dual effects on the spontaneous activities of WDR cell. These experimental findings suggest that $Mg^{2+}$ is implicated in the modulation of pain in the rat spinal cord by inhibiting the responses of WDR cell to noxious stimuli more strongly than innocuous stimuli.
The aim of the present study is to examine the brainstem sites where the electrical stimulation produces a suppression of dorsal horn neuron responses of neuropathic rats. An experimental neuropathy was induced by a unilateral ligation of L5-L6 spinal nerves of rats. Ten to 15 days after surgery, the spinal cord was exposed and single-unit recording was made on wide dynamic range (WDR) neurons in the dorsal horn. Neuronal responses to mechanical stimuli applied to somatic receptive fields were examined to see if they were modulated by electrical stimulation of various brainstem sites. Electrical stimulation of periaqueductal gray (PAG), n. raphe magnus (RMg) or n. reticularis gigantocellularis (Gi) significantly suppressed responses of WDR neurons -to both noxious and non-noxious stimuli. Electrical stimulation of other brainstem areas, such as locus coeruleus. (LC) and n. reticularis paragigantocellularis lateralis (LPGi), produced little or no suppression. Microinjection of morphine into PAG, RMg, or Gi also produced a suppression as similar pattern to the case of electrical stimulation, whereas morphine injection into LC or LPGi exerted no effects. The results suggest that PAG, NRM and Gi are the principle brainstem nuclei involved in the descending inhibitory systems responsible for the control of neuropathic pain. These systems are likely activated by endogenous opioids and exert their inhibitory effect by acting on WDR neurons in the spinal cord.
Although tail flick reflex (TFR) in rats has been used as a classic model of the nociceptive test to evaluate the action of analgesics, there have been few studies on the origin of the latent period of TFR. Present study was performed to elucidate the mechanism of increase in latency of TFR by morphine in anesthetized rats. Tail skin and dorsolateral tail nerve were stimulated electrically and EMG activities were recorded from abductor caudae dorsalis muscle participating in tail flick reflex. In the case of noxious radiant heat stimulation to tail, the tail flick tension was recorded before and after administration of morphine. Then changes in latency and conduction velocity of peripheral nerve were evaluated. The results obtained were as follows: 1) The latencies of TFR evoked by the electrical stimulation of tail skin and dorsolateral tail nerve were all within 40 ms and were elongated by several milliseconds from control after the administration of morphine. Peripheral conduction velocities of tail flick afferent nerve were within the range of 10-25 m/s. 2) The conduction velocity of peripheral nerve was significantly reduced after morphine administration, therefore the afferent time (utilization time+conduction time to spinal cord) was significantly increased. But the time for central delay and efferent time was not affected by morphine. 3) The conduction velocity under room temperature $(20-25^{\circ}C)$ was significantly reduced after morphine while that under vasodilation state $(40{\sim}42^{\circ}C)$ increased, 30 min and 45 min after morphine. The conduction velocity under vasodilation state without treatment of morphine increased continuously 4) The latency in tension response of TFR evoked by electrical stimulation was elongated by several milliseconds from control while the latency evoked by noxious radiant heat was elongated by several seconds compared with that of control. From the above results, it could be concluded that: 1) the increased latency of TFR evoked by electrical stimulation of the tail after morphine administration was due to the reducton in conduction velocity of peripheral nerve, which was the secondry effect of morphine on the peripheral vasomotion and 2) increased latency of TFR evoked by noxious radiant heat was also due to the same effect of morphine and the increase in cutaneous insulation to the noxious heat.
Journal of the korean academy of Pediatric Dentistry
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v.23
no.2
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pp.525-536
/
1996
The purpose of this study was to investigate the effect of electrical anesthesia induced by non-acupuncture point stimulation on inhibition of amplitude of digastric EMG evoked by noxious electrical stimuli in teeth and gingiva. Experiments were performed with dogs anesthetized with intraperitoneal pentobarbital sodium in an initial dose of 30mg/kg. Maintenance doses of 4.0ml/hour were given through a cannula in the femoral vein using a constant infusion pump. Anterior belly of digastric muscle was exposed and a pair of 0.1mm wire electrodes were inserted for E.M.G. recording. Bipolar electrodes were inserted into the labial and lingual surface of upper canine and the labial area of upper gingiva. Noxious stimuli were delivered to the tooth and gingiva through those electrodes by electric stimulator. Non-acupuncture point stimulation of 2Hz was delivered bilaterally to the femoral area. Amplitudes of digastric E.M.G. were measured from the oscilloscope and the monitor connected to amplifier at different intensities of electronic anesthesia of 1 volt, 4 volt and 10 volt. The inhibited rate of the amplitudes of digastric E.M.G. were analysed statistically with paired t-test. The following results were obtained : 1. Non-acupuncture point stimulation with intensities of 1 volt, 4 volt and 10 volt showed the inhibitory effect on pain of 15%, 25% and 16% in teeth and 15%, 18% and 12% in gingiva respectively 2. In tooth, statistical significance was observed between control and each group. In gingiva, there was statistical significance between control and group 1, 2 except group 3 From these results, low frequency electrical stimulation of non-acupuncture point resulted in reducing of dental and gingival pain, it could be used as adjunct to other pain control methods.
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