• The Korean Journal of Pain
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• 제34권1호
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• pp.58-65
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• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.85-96
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• 1996

Adenosine and its analogues are known to possess analgesic effects and to be involved in the opiate-induced antinociception as well. This study was designed to investigate the effects of three adenosine agonists, 5'- (N-cyclopropyl) -carboxamidoadenosine(CPCA), 5'-N-ethylcarboxamidoadeno-sine (NECA) and $N^6-cyclohexyladenosine$ (CHA) on the signal transmission in the spinal cord and also to elucidate mechanisms of their actions in the anesthetized cat. All the tested adenosine agonists(i.v,) exerted inhibitory effects on the responsiveness of the wide dynamic range (WDR) cells, the inhibitory action of CHA, an adenosine $A_1$ receptor agonist, $(80{\mu}g/Kg)$ being most weak. The intravenous CPCA, an adenosine $A_2$ receptor agonist, $(20{\mu}g\;/Kg)$ and NECA, nonspecific adenosine receptor agonist, $(20{\mu}g\;/Kg)$ inhibited the responses of WDR cells to pinch and C fiber stimulation more strongly than those to brush and A fiber stimulation. CPCA (i.v.) also suppressed the responses of WDR cells to thermal stimulus. And all the CPCA-induced inhibitions were caffeine-reversible. When CPCA was directly applied onto the spinal cord or intravenously administered into the spinal cat, on average, about three quarters of the CPCA-induced inhibitory effect was abolished. On the other hand, in the animal with spinal lesions in the ipsilateral dorsolateral area, the CPCA-induced inhibition was comparable to that observed in the spinal cats. In conclusion, this study shows that adenosine agonists strongly suppress the responses of WDR cells to pinch, C fiber stimulation and thermal stimuli mainly through the supraspinal adenosine $A_2-receptors$.

• 한국전문물리치료학회지
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• 제6권4호
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• pp.8-14
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• 1999

이 연구의 목적은 우세한 손과 그렇지 않은 손에서 방사효과가 악력에 어떤 영향을 미치는가 알아보는데 있다. 연구대상은 의료기관에 있는 30명이며 연령은 $32{\pm}9.23$세, 체중분포 $73.8{\pm}23.7$ kg이며, 신장은 $170.26{\pm}10.24$ cm 이었다. 연구 대상자들의 악력은 4가지 다른 조건에서 측정되어졌다. 첫째 조건은, 방사효과가 잠재적으로 가능한 상태에서 우세한 손의 최대악력을 측정, 둘째 조건은, 방사효과가 잠재적으로 불가능한 상태에서 우세한 손의 최대악력을 측정, 셋째 조건은, 방사효과가 잠재적으로 가능한 상태에서 우세하지 않은 손의 최대악력을 측정, 넷째 조건은, 방사효과가 잠재적으로 불가능한 상태에서 우세하지 않은 손의 최대악력을 측정하였다. 연구결과로는 어떤 조건에서도 방사효과가 잠재가능과 불가능의 최대악력비교에서 이원분산분석(two-way ANOVA) 결과 통계학적으로 어떤 차이점도 없었다(F[1, 116] = .0016, p<.05). 이 연구결과는 정상인에 있어서 방사효과가 악력에 미치는 영향을 통계학적으로 발견할 수 없다는 결론을 내렸다. 그 이유로는 방사효과가 최대악력에 미치는 영향이 10~20%의 최대 근육 수축범위이며 척추상위 억제 기전(supraspinal inhibitory mechanism)이 방사효과의 활동을 억제한다는 이론에 의한다.

• 한국전문물리치료학회지
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• 제8권4호
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• pp.81-89
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• 2001

전시냅스 억제(presynaptic inhibition)와 동시냅스 억제(homosynaptic depression)는 보행 시에 분절반사(segmental reflex)를 조절하는 두 가지 독립적인 기전이다. 근방추 피드백(feedback)은 전시냅스 억제(inhibition)를 통해 보행 시 원심성 근육 수축기에서 적절이 조절될 수 있다. 이러한 전시냅스 억제 작용은 H-reflex의 강도로 나타내질 수 있는데, 원심성 근육 수축기 동안 H-reflex의 강도가 약해지는 것으로 보아 전시냅스 억제 작용은 증가되는 것으로 보여진다. 근방추 구심성 피드백(feedback) 역시 동시냅스 억제를 통해서 조절될 수 있다. 따라서 전시냅스와 동시냅스 억제는 보행 시작 중에 반사의 기전을 조절하는 중요한 역할을 한다. 반사의 조절 기전은 알파(alpha) 운동 신경원의 흥분도와 더불어 상위 척수의 기전들을 통해서 영향받고 조절된다. 경직성 마비 환자들은 초기의 입각기, 혹은 유각기 중에 손상된 비정상 비복근 H-reflex 조절기전을 보여준다. 이러한 비정상적인 조절기전은 발바닥의 말초신경을 자극함으로써 부분적으로 회복될 수 있다.

• The Korean Journal of Physiology
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• 제22권1호
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• pp.89-100
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• 1988

Effect of clonidine on the dorsal horn cell responses to mechanical stimulations were studies in 3 spinalized cats and 10 cats with intact spinal cord. The type of dorsal horn cells was determined according to their response patterns to four graded mechanical stimulations (brush, pressure, pinch and squeeze) applied to the respective receptive fields. In the present study the results obtained only from the wide dynamic range (WDR) cells were included. The responses of the WDR cells to noxious mechanical stimuli were selectively suppressed following intravenous administration of clonidine into the experimental animals. The clonidine-induced changes in responses of the WDR cells to mechanical stimulation were not affected by naloxone or propranolol whereas effect of clonidine on WDR cell responses was almost completely abolished after intravenous administration of yohimbine. Also in the spinalized cats results parallel to those observed in cats with intact spinal cord were obtained. The results of present study strongly implies that analgesic action of clonidine can be mediated through excitation of ${\alpha}_{2}-adrenoceptor$ even at the spinal cord level without supraspinal mechanism.

• The Korean Journal of Pain
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• 제20권2호
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• pp.92-99
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• 2007

Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.129-138
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• 1989

척수 전근내 구심신경의 특성을 알아보기 위하여 고양이에서 L7 척수 전근을 전기자극하여 유발되는 동맥혈압의 변동을 관찰하였다. morphine을 정맥내 혹은 직접 척수에 투여하여 그 효과를 관찰하였으며 척수에 부분적인 손상을 가하여 척수 전근의 구심정보가 척수의 어느 부위를 통하여 중추로 올라가 승압반응을 유발하는지를 결정하여 다음과 같은 결과를 얻었다. 1. 척수전근을 C-강도, 높은 빈도로 자극하면 현저한 승압반응을 유발하였으며 낮은 빈도로 자극할 때에는 피부 혹은 근육감각신경을 자극할 때 보이는 감압반응이 유발되지 않았다. 2. 경수부위를 절단하였을 경우 승압반응이 소실되어 승압반응이 전적으로 척수 상부구조를 통하여 일어남을 알 수 있었다. 3. 승압 반응의 척수내 상행경로는 척수의 dorsolateral funiculus에 양측성으로 존재하였다. 4. 정맥내로 주사한 morphine은 척수 전근내 구심섬유가 자극되어 유발되는 승압반응을 강화시켰으나 척수에 직접 투여한 morphine은 승압반응을 억제하였다. 이상의 결과로부터 척수 전근내에 존재하는 구심성 섬유들은 기능적으로 근육 감각신경 중에 승압반응을 유발하는 C-섬유와 유사한 성질을 갖는다고 사료된다.

• The Korean Journal of Pain
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• 제18권2호
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• pp.107-112
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• 2005

Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.