• Title, Summary, Keyword: Nociception

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Evaluation of Some Flavonoids as Potential Bradykinin Antagonists

  • Choi, Hye-Sook;Chung, Sung-Hyun;Kim, Young-Joo
    • Archives of Pharmacal Research
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    • v.16 no.4
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    • pp.283-288
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    • 1993
  • Fourteen flavonoids were evaluated for their effects as potential bradykinin (BK) antagonists. The compounds were evaluatd in several in vitro and in vivo (oral administration) systems ; inhibition of BK induced contractions in isolated rat ileum and uterus, antagonistic effects of BK induced plasma extravasation, reduction of acetic acid induced withing nociception and protection from endotoxic shock. Skullcapflavone II (3), baicalein (5), 5-methoxyflavone (11), 6-methoxyflavone (12) and 2'-methoxyflavone (14) showed effects in all the tests although the order of potency were somewhat varied.

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The effect of low power GaAlAs laser stimulation on anti-nociception and spinal neuronal activity related to pain sensation in the polyarthritis of rats (다발성 관절염 실험동물 모델에서 저출력 GaAlAs 레이저 자극의 진통효능 및 통증관련 척수내 신경세포의 활성변화에 관한 연구)

  • Chang, Moon-Kyung;Choi, Young-Duk;Park, Bong-Soon
    • Journal of Korean Physical Therapy Science
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    • v.10 no.1
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    • pp.180-189
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    • 2003
  • The experiments were designated to evaluate the anti-nociceptive effect of low power laser stimulation on acupoint or non-acupoint using arthrogenic solution induced poly arthritis animal model. Evaluation of potential antinociceptive effect of low power laser on arthritis has employed measurements of the foot bending test, the development of either thermal or mechanical hyperalgesia following the arthritis induction. The analysis of thermal hyperalgesia includes Hargreaves's method. Randall-Sellitto test was utilized for evaluating mechanical hyperalgesia. In addition, the antinociceptive effect of low power laser stimulation on arthritis induced spinal Fos expression was analyzed using a computerized image analysis system. The results were summerized as follows: 1. In laser stimulation on acupoint treated animal, laser stimulation dramatically inhibited the development of pain in foot bending test as compared to those of non acupoint treated animal group and non treated animal group. 2. The threshold of thermal stimulation was significantly increased by low power laser stimulation on acupoint as compared to that of non treated control group. 3. Laser stimulation on acupoint dramatically attenuated the development of mechanical hyperalgesia as compared to that of non treated group. 4. Low power laser stimulation on acupoint significantly suppressed arthritis induced Fos expression in the lumbar spinal cord at 3 week post arthritis induction. In conclusion, the results of the present study demonstrated that low power laser stimulation on acupoint has potent anti-nociceptive effect on arthritis. Additional supporting data for an antinociceptive effect of laser stimulation was obtained using Fos immunohistochemical analysis on spinal cord section. Those data indicated that laser stimulation induced antinociception was mediated by suppression of spinal neuron activity in pain sensation.

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PRELIMINARY STUDY OF NEUROSENSORY RECOVERY AFTER BSSRO (악교정 수술 후 발생하는 신경회복에 대한 연구 I)

  • Lee, Dong- Keun;Jo, I-Su;Min, Seung-Ki;Oh, Seung-Hwan;Jeong, Chang-Ju;Lee, Eun-Tak
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.23 no.2
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    • pp.144-154
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    • 2001
  • Dysfunction of the inferior alveolar nerve indicated by various degree of numbness of the lower lip and chin is one of the few drawbacks of mandibular osteotomy, especially Bilateral Sagittal Split Ramus Osteotomy(BSSRO) and genioplasty. Although it has been recorded throughout the history of this techniques, it is true etiology poorly understood. In this study, 22 consecutive patients under class III malocclusiion impression and undergoing orthognathic surgery(BSSRO only 11 case, BSSRO with genioplasty 11 case) were studied using 4 neurosensory test(static light touch, directional discrimination, two-point discrimination, pin pressure nociception) with post OP 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 24 weeks, On control group, 10 members without trauma and nerve damage history, nerve test was accomplished. We concluded majority of patients return of sensation during post operative 24 weeks. Althought immediate nerve deficit are 92.2%, 97.2% 88.9% these are recovered to 25%, 35.72%, 10.71% at 24 weeks. Nerve recovery rate increased prominently between post 4 weeks and 8 weeks. There is no statistically difference about neurosensory deficit among the chin area. Neurosensory deficit more severe when the BSSRO with genioplasty group than the only BSSRO group. Immediate neurosensory deficit is larger left side than right side but after 6 months, there is no significantly difference between left side and right side. Static light touch and pin pressure nociception are more sensitive method of neurosensory deficit than two point discrimination.

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Diverse characters of Brennan's paw incision model regarding certain parameters in the rat

  • Kumar, Rahul;Gupta, Shivani;Gautam, Mayank;Jhajhria, Saroj Kaler;Ray, Subrata Basu
    • The Korean Journal of Pain
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    • v.32 no.3
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    • pp.168-177
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    • 2019
  • Background: Brennan's rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. Methods: Separate groups of Sprague-Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and $10{\mu}g$ of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. Results: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. Conclusions: Based upon current observations, Brennan's rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Effects of Intraperitoneal N-methyl-D-aspartate (NMDA) Administration on Nociceptive/Repetitive Behaviors in Juvenile Mice

  • Kim, Seonmin;Kim, Do Gyeong;Gonzales, Edson luck;Mabunga, Darine Froy N.;Shin, Dongpil;Jeon, Se Jin;Shin, Chan Young;Ahn, TaeJin;Kwon, Kyoung Ja
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.168-177
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    • 2019
  • Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

RESPONSE CHARACTERISTICS OF VENTRAL POSTEROMEDIAL THALAMIC NOCICEPTIVE NEURONS IN THE ANESTHETIZED RAT (마취된 흰 쥐 시상의 복후내측핵내 유해성 뉴론의 특성)

  • Lee, Hyung-Il;Park, Soo-Joung
    • Restorative Dentistry and Endodontics
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    • v.27 no.6
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    • pp.587-599
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    • 2002
  • Extracellular single unit recordings were made from the ventral posteromedial thalamic (VPM) nociceptive neurons to determine mechanoreceptive field (RF) and response properties. A total of 44 VPM thalamic nociceptive neurons were isolated from rats anesthetized with urethane-chloralose. Based on responses to various mechanical stimuli including touch, pressure and pinch applied to the RF, 32 of 44 neurons were classified as nociceptive specific (NS) neuron. The other 12 neurons, classified as wide dynamic range (WDR), showed a graded response to increasingly intense stimuli, with a maximum discharge to noxious pinch. The VPM nociceptive neurons showed various spontaneous activity ranged from 0-6 Hz. They were located throughout the VPM, and had an contralateral RF including mainly intraoral (and perioral) regions. The RF size was relatively small, and very few neurons had a receptive field involving 3 trigeminal divisions. The NS neurons activated only by pressure and pinch stimuli had high mechanical thresholds compared to WDR neurons activated also by touch stimuli. The VPM nociceptive neurons were tested with suprathershold graded mechanical stimuli. Most of 21 NS and 8 WDR neurons showed a progressive increase in number of spikes as mechanical stimulus intensity was increased. In some neurons, the responses reached a peak before the highest intensity was given. Application of 5 mM $CoCl_2{\;}(10{\;}{\mu}\ell)$ solution to the trigeminal subnucleus caudalis did not produce any significant changes in the spontaneous activity, RF size, mechanical threshold, and response to suprathreshold mechanical stimuli of 9 VPM nociceptive neurons tested. 17 of 33 VPM nociceptive neurons responded to noxious heat as well as noxious mechanical stimuli applied to their RF. Application of the mustard oil, a small-fiber excitant and inflammatory irritant, to the right maxillary first molar tooth pulp induced an immediate but short-lasting neuronal discharges upto approximately 4 min in 16 of 42 VPM nociceptive neurons. These results suggest that VPM thalamic nucleus may contribute to the sensory discriminative aspect of orofacial nociception.

Antinociceptive Effects of Intrathecal Melatonin on Formalin- and Thermal-induced Pain in Rats (포르말린 및 열성 자극 유발 통증에 대한 척수강 Melatonin의 항침해 효과)

  • Chung, Sung Tae;Jin, Won Jong;Bae, Hong Beom;Kim, Seok Jai;Choi, Jeong Il;Kang, Myung Woo;Jeong, Chang Young;Yoon, Myung Ha
    • The Korean Journal of Pain
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    • v.19 no.2
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    • pp.137-141
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    • 2006
  • Background: It has been known that melatonin is involved in the modulation of nociceptive transmission. However, the effect of melatonin administered spinally has not been examined. Therefore, we examined the effect of melatonin on the formalin-induced or thermal-induced nociception at the spinal level. Methods: Intrathecal catheter was inserted into the subarachnoid space of male Sprague-Dawley rats. Pain was assessed by formalin test (induced by injection of $50{\mu}l$ of a 5% formalin solution to the hindpaw) or Hot-Box test (induced by radiant heat application to the hindpaw). The effect of intrathecal melatonin was examined on flinching behavior in the formalin test or withdrawal response in Hot-Box test. Results: Intrathecal melatonin produced a limited, but dose-dependent reduction of the flinching response during phase 1 and 2 in the formalin test. In addition, melatonin delivered at evening also decreased the flinching response in both phases of the formalin test. Melatonin restrictively increased the withdrawal latency in Hot-Box test. Conclusions: These results suggest that melatonin is active against the formalin- and thermal-induced nocicpetion at the spinal level, but the effect is limited.

Blockade of Trigeminal Glutamate Recycling Produces Anti-allodynic Effects in Rats with Inflammatory and Neuropathic Pain

  • Yang, Kui-Ye;Lee, Min-Kyung;Park, Min-Kyoung;Son, Jo-Young;Ju, Jin-Sook;Ahn, Dong-Kuk
    • International Journal of Oral Biology
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    • v.42 no.3
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    • pp.129-135
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    • 2017
  • The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-$1{\beta}$-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-$1{\beta}$ (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-${\beta}$-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-$1{\beta}$-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-$1{\beta}$ or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in na?ve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

Effects of Somatostatin on the Responses of Rostrally Projecting Spinal Dorsal Horn Neurons to Noxious Stimuli in Cats

  • Jung, Sung-Jun;Jo, Su-Hyun;Lee, Sang-Hyuck;Oh, Eun-Hui;Kim, Min-Seok;Nam, Woo-Dong;Oh, Seog-Bae
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.5
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    • pp.253-258
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    • 2008
  • Somatostatin (SOM) is a widely distributed peptide in the central nervous system and exerts a variety of hormonal and neural actions. Although SOM is assumed to play an important role in spinal nociceptive processing, its exact function remains unclear. In fact, earlier pharmacological studies have provided results that support either a facilitatory or inhibitory role for SOM in nociception. In the current study, the effects of SOM were investigated using anesthetized cats. Specifically, the responses of rostrally projecting spinal dorsal horn neurons (RPSDH neurons) to different kinds of noxious stimuli (i.e., heat, mechanical and cold stimuli) and to the $A{\delta}$ -and C-fiber activation of the sciatic nerve were studied. Iontophoretically applied SOM suppressed the responses of RPSDH neurons to noxious heat and mechanical stimuli as well as to C-fiber activation. Conversely, it enhanced these responses to noxious cold stimulus and $A{\delta}$-fiber activation. In addition, SOM suppressed glutamate-evoked activities of RPSDH neurons. The effects of SOM were blocked by the SOM receptor antagonist cyclo-SOM. These findings suggest that SOM has a dual effect on the activities of RPSDH neurons; that is, facilitation and inhibition, depending on the modality of pain signaled through them and its action site.

GABAB Receptor Modulation on the Antinociception of Intrathecal Sildenafil in the Rat Formalin Test (쥐의 포르말린 시험에서 척수강 Sildenafil의 항통각효과에 대한 GABAB 수용체 조절성)

  • Kim, Woong Mo;Yoon, Myung Ha;Lee, Hyung Gon;Han, Yong Gu;Kim, Yeo Ok;Huang, Lan Ji;Cui, Jin Hua
    • The Korean Journal of Pain
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    • v.20 no.2
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    • pp.106-110
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    • 2007
  • Background: A phosphodiesterase 5 inhibitor, sildenafil, has been effective against nociception. Several lines of evidence have demonstrated the role of the GABAergic pathway in the modulation of nociception. The impact of the GABA receptors on sildenafil was studied using the formalin test at the spinal level. Methods: Male SD rats were prepared for intrathecal catheterization. The formalin test was induced by subcutaneous injection of formalin solution. The change in the activity of sildenafil was examined after pre-treatment with GABA receptor antagonists ($GABA_A$ receptor antagonist, bicuculline; $GABA_B$ receptor antagonist, saclofen). Results: Intrathecal sildenafil dose-dependently attenuated the flinching observed during phase 1 and 2 in the formalin test. The antinociceptive effect of sildenafil was reversed by the $GABA_B$ receptor antagonist (saclofen) but not by the $GABA_A$ receptor antagonist (bicuculline) in both phases. Conclusions: Intrathecal sildenafil suppressed acute pain and the facilitated pain state. The antinociception of sildenafil is mediated via the $GABA_B$ receptor, but not the $GABA_A$ receptor, at the spinal level.