• The Korean Journal of Physiology and Pharmacology
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• 제13권5호
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• pp.379-383
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• 2009

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.191-191
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• 1996

BQ-123, a selective $ET_{A}$ receptor antagonist, reverses various responses induced by Endothelin-1 and it has been reported that BQ-123 ameliorates the cerebrovascular constriction, hypertension, and decrease of blood flow. Previously, we announced that the level of Endothelin-2 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of $ET_{A}$ receptor antagonist, BQ-123(10nmol) was done for visualizing the role of endothelin-1 on the pathogenesis of EAE. BQ-123 apparently blocked the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model following BQ-123, suggests that BQ-123 is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• The Korean Journal of Physiology
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• 제28권1호
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• pp.105-111
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• 1994

The present study was carried out to determine the effects of intracisternal administration of three doses of bombesin $(0.001,\;0.01\;and\;0.1\;{\mu}g)$ on afferent somatosensory transmission in single neurons of the spinal trigeminal nucleus of anesthetized rats. Lower doses $(0.001\;{\mu}g)$ of bombegin did not change the afferent sensory transmission. Medium doses $(0.01\;{\mu}g)$ of bombesin significantly (p p<0.01) facilitated afferent sensory transmission in the 6 to 30 min post-drug period, but higher doses $(0.1\;{\mu}g)$ inhibited responsiveness of spinal trigeminal neurons in the 16 to 35 min post-drug period. The results indicate that endogenous bombesin-like peptide present in the spinal trigeminal nucleus may participate in the processing of the somatosensory information arising from the face.

• 대한약리학회지
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• 제14권1_2호
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• pp.13-23
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• 1978

1) Urethane 마취가토(痲醉家兎)의 내뇌(腦內)(측뇌실(刻腦室) 또는 소뇌연수조내(小腦延髓槽內)에 norepinephrine (NE), clonidine을 주입(注入)할 때 일어나는 심박감소(心搏減少), 혈압하강(血壓下降)에 관한 이들 약물(藥物)의 작용점(作用點)을 조사(調査)할 것을 시도(試圖)하였다. 2) NE의 뇌내주입(腦內注入)은 심박감소(心搏減少)를 일으켰으나 혈압(血壓)에 미치는 영향(影響)은 뚜렷치 않았다. Clonidine은 심박감소(心搏減少), 혈압하강(血壓下降)을 일으켰다. 3) 측뇌실내주입(刻腦室內注入) 소뇌연수조내주입간(小腦延髓槽內注入間)에는 NE, clonidine, phenylephrine, isoproterenol의 심박(心搏), 혈압효과(血壓效果)에 차이(差異)가 없었다. 또 NE에 의한 심박감소효과(心搏減少效果)의 출현(出現)은 소뇌연수조내주입시(小腦延髓槽內注入時) 더 빨랐다. 4) 약(約) 2시간(時間) 간격(間隔)으로 NE를 반복(反復) 주입(注入)할 때 심박효과(心搏效果)에는 거의 변동(變動)이 없었으나 혈압효과(血壓效果)는 반복주입(反復注入)함에 따라 혈압상승효과(血壓上昇效果)가 현저(顯著)히 나타났다. Clonidine의 심박감소(心搏減少) 및 혈압하강효과(血壓下降效果)는 반복주입(反復注入)에 따라 점차 약화(弱化)되었다. 5) NE 주입후(注入後) NE 효과(效果)가 지속(持續)하고 있을 때 clonidine은 더 이상(以上)의 심박감소(心搏減少)를 일으키지 않고, 혈압하강(血壓下降)도 일으키지 않았다. Clonidine 주입후(注入後) clonidine 효과(效果)가 지속(持續)하고 있을 때 NE는 더 이상(以上)의 심박감소(心搏減少)를 일으키지 않았고 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. 6) Regitine 또는 desmethylimipramine의 뇌내주입후(腦內注入後) NE는 심박(心搏)에 거의 변동(變動)을 일으키지 않았으나 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. Clonidine은 심박(心搏), 혈압(血壓)에 거의 변동(變動)을 일으키지 않았다. 7) Reserpine 처리가토(處理家兎)에서는 NE는 심박증가(心搏增加)와 혈압상승(血壓上昇)을 일으켰으며, clonidine은 심박(心搏)에는 거의 변동(變動)을 일으키지 않았고 경미(輕微)한 혈압상승(血壓上昇)을 일으켰다. 8) NE 및 clonidine에 의한 심박감소(心搏減少), clonidine에 의한 혈압하강(血壓下降)은 주(主)로 presynaptic ${\alpha}$-adrenoceptor를 중개(仲介)하여 일어나나, NE 및 clonidine에 의한 혈압상승(血壓上昇)은 presynaptic site 이외(以外)의 부위(部位)를 중개(仲介)하여 일어나는것 같다.

• 치위생과학회지
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• 제15권6호
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• pp.800-806
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• 2015

이 연구는 triptolide와 L-NAME의 측두하악관절 통증조절효과를 확인하기 위하여 포르말린으로 유도된 측두하악관절 통증모델에서 triptolide와 L-NAME의 소뇌연수조 내 각각의 얄물의 단독 투여에 따른 통증행위반응과 두 약물의 병용 투여에 따른 상호작용이 통증행위반응에 미치는 영향을 평가하여 다음과 같은 결과를 얻었다. 먼저, 관절강 내로 주입한 5% 포르말린($30{\mu}l$)은 유의한 통증행위반응을 유발하였고, 2차 통증행위반응 관찰 시 포르말린 주입 전 $1{\mu}g/10{\mu}l$ triptolide 투여군($163.33{\pm}29.11$회)은 포르말린군($308{\pm}33.04$회)과 비교 시 통증행위반응이 유의하게 감소하였다. $0.1{\mu}g/10{\mu}l$의 L-NAME 투여군의 1, 2차 통증행위반응의 결과, 각각 $5.80{\pm}3.75$회, $92.30{\pm}16.04$회로 포르말린 주입군 $25.4{\pm}6.59$회, $285.60{\pm}29.93$회와 비교 시 유의하게 감소되었다. 다음으로, $1{\mu}g/10{\mu}l$의 triptolide와 $0.01{\mu}g/10{\mu}l$의 L-NAME 병용 투여군에서 1, 2차 통증행위반응이 $0.80{\pm}0.80$회, $96.50{\pm}26.16$회로 나타나 $22.50{\pm}19.15$회, $163.33{\pm}29.11$회로 나타난 $1{\mu}g/10{\mu}l$ trtiptolide군과 비교 시 유의하게 통증행위반응이 경감되었다. 이러한 연구결과는 측두하악관절 통증조절의 예방 및 치료에 있어 활용가능한 천연물로 triptolide가 제시될 수 있으며, 천연물과 화합물들의 병용 투여를 통해 그 효과를 증가시킬 수 있을 것으로 기대된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.192-192
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• 1996

Endothelin has $ET_{A}$ type and $ET_{B}$ type receptors, and it has been thought that ET-1 proves vasoconstriction effect via $ET_{A}$ receptor and vasodilation via $ET_{B}$ receptor. Recently, it has been reported that $ET_{B}$ receptor is also related to the vaso-constriction. Bosentan is a $ET_{A+B}$ receptor antagonist, and proves it's effect on trauma and ischemia. We already announced that the level of Endothelin-1 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of Bosentan, $ET_{A+B}$ receptor antagonist, (300nmol/body) was done for observing the role of endothelin-1 on the pathogenesis of EAE. Bosentan ameliorated the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model suggests that Bosentan is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.425-429
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• 2009

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicininduced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

• International Journal of Oral Biology
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• 제37권3호
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• pp.121-129
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• 2012

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 ${\mu}g$ of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 ${\mu}g$) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.

• The Korean Journal of Pain
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• 제13권2호
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• pp.143-148
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• 2000

Background: Trigeminovascular system is implicated in the pathophysiology of the headache in migraine. This study was designed to evaluate the pattern of Fos protein expression in trigeminal nociceptive central pathway after meningeal stimulation of rats by capsaicin. Methods: The expression of Fos protein was examined by immunohistochemistry in thalamus, brainstem and upper cervical cord (at three levels corresponding to obex, 0.8 mm and 2 mm below obex) 2 hours after intracisternal injection of either diluted capsaicin solution (0.1 ml, $61{\mu}g/ml$) or normal saline (0.1 ml) through a catheter placed in the cisterna magna, or following epidural instillation of diluted capsaicin solution in urethane-anesthetized Sprague-Dawley rats. Results: Fos immunoreactivity was strongly expressed within lamina I, II of bilateral trigeminal nucleus caudalis (TNC) after cisternal capsaicin injection and magnitude of expression was greatest at level 2.0 mm below obex. Epidural capsaicin caused much less labelling than cisternal capsaicin. Fos positive cells were also observed in area postrema, nucleus of the solitary tract, medullary reticular nucleus and midline nuclear groups of the thalamus with similar intensity between capsaicin and control group. Conclusions: These results indicate that the injection of capsaicin into the cisterna magna is an effective stimulus for the induction of Fos protein within TNC through activation of trigeminovascular afferents and this animal model can be useful for the evaluation of the pathophysiology and drug development in migraine and related headache.

• Applied Microscopy
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• 제3권1호
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• pp.23-28
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• 1973

토끼의 족서부 피하로 Bovine Gamma Globulin과 Ineomplete Freud's Adjuvant를 주입한 후 국소임파절내의 항체생산 세포인 형질세포의 rER을 경시적으로 관찰한 결과를 요약하면 다음과 같다. (1) 항원투여전의 형질세포의 rER 는 일반적으로 편평낭상 (flattened sac) 을 정하고, 항원 투여 후 3 일째에는 일반적으로 소포상 (vesic lar) 를 그리고 7 일내지 10 일째에는 공포상 (vacuolar) 를 정하고 그 강내에는 intracisternal granule 이 다수 출현하며 20 일째에는 다시 확장낭상 내지는 편평낭상을 정하게 된다. 이상의 연구성적으로 보아 편평낭상을 정하는 형질세포의 rER에 항원성 자극을 가하면 처음에는 소포상으로 되었다가 공포상으로 변화하며, 항원 성자극이 소퇴하면 다시 편평낭상으로 복귀된다고 생각된다.