• Journal of Korean Neurosurgical Society
• /
• 제42권6호
• /
• pp.462-469
• /
• 2007

Objective : This study characterized the neurons in the lumbosacral cord that express phospho ERK (pERK) after distension or irritation of the bladder, and their relation to the vanilloid receptor 1 (VR1) positive primary afferents. Methods : Mechanical distension and chemical irritation of the bladder were induced by intravesical injection of the saline and mustard oil, respectively. Spinal neurons expressing pERK and the primary afferent fibers were characterized using multiple immunofluorescence for neurokinin 1 (NK1), neuronal nitric oxide synthetase (nNOS) and VR1. Results : Neurons in lamina I, medial dorsal horn (MDH), dorsal gray commissure (DGC) and sacral parasympathetic nucleus (SPN) were immunoreactive for pERK after either mechanical or chemical stimulation. The majority of pERK positive cells were positive for NK1 in lamina I and SPN, but not in the DGC. Most of pERK positive cells are not stained for nNOS except in a small population of the cells in the SPN and DGC. Contacts between perikarya and dendrites of pERK-positive cells and terminals of primary afferents expressing VR1 were identified in lamina I. lateral collateral path (LCP) and SPN. Conclusion : In this study, the lumbosacral neurons activated by mechanical and chemical stimulation of the urinary bladder were identified with expression of the pERK, and also provided the evidence that VR1-positive primary afferents may mediate the activation of these neurons.

• The Korean Journal of Physiology
• /
• 제24권1호
• /
• pp.171-180
• /
• 1990

In 19 cats anesthetized with ${\alpha}-chloralose$ effects of taurine and ${\beta}-alanine$ on the responses of wide dynamic range (WDR) cells to mechanical, chemical and thermal stimuli were investigated in the lumbar spinal cord of the cat. Also studied was an interaction of strychnine with taurine in affecting the activities of WDR cells. Following intravenous administration of taurine, the responses of WDR cells to all types of mechanical stimuli were markedly enhanced, demonstrating that the response to pressure was most sensitive to taurine action. When the receptive field was exposed to thermal stimuli ($50^{\circ}C$) for 20 sec. taurine increased activity of WDR cell to 169.5% of the control value. The $K^{+}$-induced activation of WDR cells was invariably suppressed after taurine administration. Intravenously administered strychnine remarkably reduced the enhanced response of WDR cell to natural stimuli resulting from intravenous administration of taurine. Also ${\beta}-alanine$ markedly activated the response of spinal dorsal horn cell to natural mechanical stimuli. These findings suggest that neutral amino acid and its derivative such as ${\beta}-alanine$ and taurine can enhance the response of WDR cells to different stimuli in cats.

• Journal of Acupuncture Research
• /
• 제15권2호
• /
• pp.17-28
• /
• 1998

The present study was designed to investigate the effect of different stimulation-duration of high frequency electroacupuncturet(EA) treatment on the neuronal activities in the spinal cord and brainstem using Fos immunohistochemical technique. Three different stimulus-duration was used in this experiment : 30minutes, 1 hour and 2 hours. The summerized results were summerized as follow : 1. The number of Fos expression was significantly increased in the spinal cord dorsal horn depending upon the increase of stimulus-duration (P<0.05). Otherwise, there was no significant difference between 30 minutes EA treated group and anesthetic control. 2. High frequency EA biphasic stimulation significantly enhanced the Fos expression in the DR, middle and rostral portion of PAG LD, and caudal PAG LV after 1 hour and 2 hours treatment. The number of Fos immunoreactive neuron in the brainstem was increased accorcting to the length of stimulus-duration. Those results indicate that at least 1 hour EA treatment was necessary to increase the neuronal activities in the spinal cord and brainstem. Those basic data from this study can be applied to establish the effective treatment of EA for pain control in the clinical field.

• The Korean Journal of Pain
• /
• 제24권3호
• /
• pp.131-136
• /
• 2011

Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

• 대한한의학회지
• /
• 제23권2호
• /
• pp.97-107
• /
• 2002

Objective : Acupuncture is a method used to treat many kinds of pain in oriental cultural medicine. Especially when hetero-segmental area acu-points are stimulated, the therapeutic effects of pain control have more critical properties than other methods of acupuncture. However, the mechanism of pain control by acupuncture is contradictory so far. The present study examined the effects of electroacupuncture (EA) applied to the acu-point of the hetero-segmental area on modulation of formalin-induced pain in Sprague-Dawley rats. Methods : In order to apply EA to acu-points in the plantar area of right forepaws, a pair of Teflon-coated stainless steel wires were implanted in HT 7 (Shin-Moon) and PC 7 (Dae-Reung) 7 days before the behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\;}\mu\textrm{l}$) into the lateral plantar region of the left hind paw. EA was delivered by a constant DC current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. c-Fos protein expression was measured in the lumbar spinal cord at 2 hr and 4 hr after formalin injection. Results : Behavioral responses including favoring, flinching and biting occurred in the biphasic pattern, such as the 1st phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited the behavioral responses. Injection of formalin expressed c-Fos protein on the ipsilateral dorsal horn neurons in L3 - L5 and the expression was sustained more than 4 hrs after formalin injection. However, EA decreased c-Fos protein expression at dorsal horn neurons in the lumbar spinal cord till 4hrs after formalin injection. Conclusions : These results suggest that EA modulates formalin-induced pain and this inhibitory action may be elicited by the descending inhibitory system.

• 한방재활의학과학회지
• /
• 제21권2호
• /
• pp.101-123
• /
• 2011

Objectives : The aim was to study the effect of bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model. Methods : We enforced a bee venom pharmacopuncture therapy with different concentration on rheumatoid arthritis rat model by the intradermal injection of chicken type II collagen emulsified. 14 days after the onset of the rheumatoid arthritis rat model, a fixed volume of bee venom was daily injected to ST-35 acupoint in the rat's knee joint for 2-3 weeks. The hind paw volume, arthritic index, arthritic flexion pain test, pain threshold, and serum analysis (CRP, $PGE_2$, ALT, AST) were analyzed, and the expression profiles of COX-2, c-fos, and substance-P at the dorsal horn region of the spinal cord and subchondral bone of the knee joint were also analyzed by using the immunohistochemistry. Results : After the treatment of rheumatoid arthritis rats with bee venom pharmacopuncture, the paw volume of edema of arthritic rats were almost restored to the level of normal group, and behavior tests were very effective. Also the evaluation on the blood serum analysis was remarkable. COX-2, c-fos, and substance-P positive cells in the immunohistological section of dorsal horn region of the spinal cord and subchondral bone of the knee joints were significantly decreased. also the bee venom pharmacopuncture was effective to alleviate their rheumatoid arthritic inflammation cytokine inhibition as regards to the behavior tests and joint histological appearance. Conclusions : Based on the results in this study, bee venom pharmacopuncture with concentrated treatment condition was very effective in low fixed quantity and progressive low increased quantity.

• Journal of Acupuncture Research
• /
• 제20권3호
• /
• pp.15-23
• /
• 2003

Objective : The role of high frequency 120 Hz electroacupuncture(EA) in carrageenan-induced pain was studied by examining the alnalgesic effects, and prostaglandin $E_2(PGE_2)$ levels measurement and spinal N-methyl-D-aspartate(NMDA) receptor expression. Inflammation was induced by an intraplantar injection of 1% carrageenan into the right hind paw. Method : Bilateral EA stimulation with 120 Hz were delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via the needles for a total of 30 min duration in carrageenan-injected rats. Results : EA stimulation showed significant analgesic effects as measured by analgesy-meter at all time points tested compared with controls. Three hours after carrageenan injection, PGE2 levels were measured by commercial kit. EA significantly inhibited PGE2 production in the right paw. The number of NR1 and NR2A, NMDA receptor, immunoreactive neurons was significantly increased in the superficial dorsal horn(laminae I-II) and nucleus proprius(laminae III-IV) of ipsilateral spinal cord at L4-5. But the number of carrageenan-induced NR1 and NR2A immunoreactive neuron, especially NR1 immunoreaction in the superficial dorsal horn, was reduced by 120 Hz EA stimulation. Conclusions : These results indicate that NMDA receptors may mediate transmission of nociceptive information originating in tissue inflammation of hind paw and high frequency 120 Hz EA stimulation have an alleviating action against local inflammatory pain.

• Korean Journal of Acupuncture
• /
• 제36권4호
• /
• pp.264-273
• /
• 2019

Objectives : Microglia play a crucial role in electroacupuncture (EA) analgesia on neuropathic pain. The role of chemokines in producing analgesic effects of EA, however, is largely unknown. In the present study, we investigated the role of chemokines in producing analgesic effects of EA in the neuropathic pain model. Methods : Sprague-Dawley rats were randomly assigned into three groups (anesthetized group (ANE), non-acupoint EA group (NAP), and ST36 - GB34 EA group (ACU)). Neuropathic pain was induced by tight ligation of L5 spinal nerve. Mechanical and thermal hypersensitivity of hind paw was tested. Western blot tests and immunofluorescence assay for C-C motif chemokine ligand 2 (CCL2) levels and microglia activation were performed on spinal cord L5/6. EA was treated once daily from the 3rd day after surgery for 5 days. Results : EA treatments applied to ST36 and GB34 significantly reduced both mechanical and thermal hypersensitivity after two and three times of treatment, respectively. While CCL2 expression significantly increased in neuropathic rats, it was significantly reduced in the ACU. In addition, co-localization of CCL2 and activated microglia significantly decreased in the ACU compared to those of ANE and NAP in the spinal cord L5/L6 dorsal horn. Conclusions : The present results suggest that EA applied to ST36 and GB34 modulates the reduction of CCL2 release from the injured neurons and consequently decreases microglia activation in the spinal cord. Regulation of chemokine induced spinal activation of microglia plays a key role in analgesic effects of EA in the rat model of neuropathic pain.

• Journal of Korean Neurosurgical Society
• /
• 제52권6호
• /
• pp.509-512
• /
• 2012

Objective : The purpose of this study is to evaluate neuroprotective effect of sacral neuromodulation in rat spinal cord injury (SCI) model in the histological and functional aspects. Methods : Twenty-one female Sprague Dawley rats were randomly divided into 3 groups : the normal control group (CTL, n=7), the SCI with sham stimulation group (SCI, n=7), and the SCI with electrical stimulation (SCI+ES, n=7). Spinal cord was injured by dropping an impactor from 25 mm height. Sacral nerve electrical stimulation was performed by the following protocol : pulse duration, 0.1 ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration, 4 weeks. Both locomotor function and histological examination were evaluated as scheduled. Results : The number of anterior horn cell was $12.3{\pm}5.7$ cells/high power field (HPF) in the CTL group, $7.8{\pm}4.9$ cells/HPF in the SCI group, and $6.9{\pm}5.5$ cells/HPF in the SCI+ES group, respectively. Both the SCI and the SCI+ES groups showed severe loss of anterior horn cells and myelin fibers compared with the CTL group. Cavitation and demyelinization of the nerve fibers has no significant difference between the SCI group and the SCI+ES group. Cavitation of dorsal column was more evident in only two rats of SCI group than the SCI+ES group. The locomotor function of all rats improved over time but there was no significant difference at any point in time between the SCI and the SCI+ES group. Conclusion : In a rat thoracic spinal cord contusion model, we observed that sacral neuromodulation did not prevent SCI-induced myelin loss and apoptosis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권4호
• /
• 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 $A\;{\delta}-fiber$.