• Natural Product Sciences
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• v.9 no.4
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• pp.256-259
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• 2003

The pet ether extract of Caesalpinia pulcherrima, leaves was studied for its antinociceptive, anti-inflammatory and antipyretic property. The extract at doses of 50 and 200 mg/kg, p.o., significantly (p<0.05) reduced the number of writhing induced by acetic acid and inhibited the late phase (20-30 min) in formalin test in mice. The extract failed to increase the pain threshold level in tail immersion test in mice. In carrageenan induced paw edema in rats and in acetic acid induced increase in vascular permeability test in mice, the extract (50-600 mg/kg, p.o.) failed to produce any significant activity. While in cotton pellet granuloma test, the extract at doses of 200 and 600 mg/kg (p.o.) significantly (p<0.05) reduced the granuloma formation and was comparable to reference drug, dexamethasone. In ethylpheylpropiolate ear edema test 0.5 mg and 1 mg/ear application of extract significantly (p<0.05) inhibited ear edema. In yeast induced hyperthermia in rats, the extract did not produce any reduction in temperature. The results suggest that the extract acts peripherally to produce analgesic action and anti-inflammatory activity through steroidal mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.187-192
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• 2012

In the present study, the antinociceptive profiles of hop extract were characterized in ICR mice. Hop extract administered orally (from 25 to 100 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Antinociceptive action of hop extract was maintained at least for 60 min. Moreover, cumulative response time of nociceptive behaviors induced with intraplantar formalin injection was reduced by hop extract treatment during the 2nd phases. Furthermore, the cumulative nociceptive response time for intrathecal injection of substance P ($0.7{\mu}g$) or glutamate ($20{\mu}g$) was diminished by hop extract. Intraperitoneal pretreatment with naloxone (an opioid receptor antagonist) attenuated antinociceptive effect induced by hop extract in the writhing test. However, methysergide (a 5-HT serotonergic receptor antagonist) or yohimbine (an ${\alpha}_2$-adrenergic receptor antagonist) did not affect antinociception induced by hop extract in the writhing test. Our results suggest that hop extract shows an antinociceptive property in various pain models. Furthermore, the antinociceptive effect of hop extract may be mediated by opioidergic receptors, but not serotonergic and ${\alpha}_2$-adrenergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.349-355
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• 2015

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

• Korean Journal of Pharmacognosy
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• v.44 no.2
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• pp.188-192
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• 2013

Acer tegmentosum which is belongs to Aceraceae has been widely used as a traditional medicine for the treatment of lots of diseases including pain management. In this study, we evaluated the anti-nocicepitve effects of methanolic extract of A. tegmentosum (MAT) in mice using various pain models. MAT presented strong and dose-dependent anti-nociceptive activities on thermal nociception models such as tail-immersion test and hot plate test. Moreover, acetic acid-induced chemical nociception was signigicantly reduced by MAT treatment. We could confirm MAT's central and peripheral analgesic properties by formalin test. We also found that the pre-treatment of opioid receptor antagonist did not alter the MAT's anti-nociception, suggesting opioid receptor is not involved in analgesic activity of MAT. Based on our results, we could conclude that MAT may be possibly used as an anti-nociceptive agent for the treatment of various nociceptive pains.

• Korean Journal of Pharmacognosy
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• v.54 no.2
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• pp.61-65
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• 2023

Clerodendrum trichotomum has been widely used as a traditional medicine for the treatment of numerous diseases, including pain management. However, there have been extremely limited pharmacological and phytochemical studies on Clerodendrum trichotomum up to now. In this study, we investigated the effects of the methanolic extract of Clerodendrum trichotomum (MCT) on nociceptive pain in mice. Our finding demonstrate that MCT treatment significantly extended the latency time in both the tail-immersion test and hot-plate test. Additionally, MCT treatment reduced acetic acid-induced writhing motions. These results suggest that MCT possesses strong anti-nociceptive activities against thermal and chemical nociception. In the formalin test, mice fed with MCT exhibited reduced licking time during both the early and late phases, thereby confirming the therapeutic potential of MCT in central and peripheral nociception. Furthermore, in combination tests using naloxone, the MCT-mediated anti-nociception was slightly reduced, indicating that MCT might act as a partial opioid receptor agonist. Based on these results, MCT may be a valuable candidate for the development of anti-nociceptive agents.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.39-49
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• 2007

목적 : 봉독으로 유발된 통각수용의 강도와 봉독으로 나타나는 항통각수용(통각억제성)의 강도를 쥐의 포르말린 테스트를 통해 상호관련됨을 확인하고 capsaicin과 bradykinin으로 통증 유발된 쥐의 자발적인 통증행동(핥기횟수측정; LN), 꼬리경타시험(TFL)과 열판시험(HPL)을 통해 봉독의 항통각수용(통각억제)작용을 재확인 하고자 하였다. 방법 : 쥐의 뒷다리에 통증유도 물질인 Capsaicin 또는 Bradykinin을 20${\mu}l$를 주사하여 동통을 유발하고 자발적 통증행동인 핥기횟수측정(LN), 꼬리경타기간(TFL)과 열판 위에서의 온도자극에 쥐가 반응하는 시간을 측정(HPL)하는 실험을 봉독을 주입하거나, 몰핀을 주입하거나, 아무것도 주입하지 않고 통증유발만 시킨 이후에 각각 시행하였다. 결과: 1. Capsaicin 또는 Bradykinin으로 동통유발 후 LN은 두드러증가를 보임, HPL은 감소를 TFL은 두드러진 감소를 나타내었다. 2. 봉독이나 몰핀 주입 30분 후에 Capsaicin으로 동통유발 이후 LN은 봉독과 몰핀에서 모두 현격한 감소를, HPL은 봉침은 현격한 증가를, 몰핀에서는 감소를, TFL은 봉침과 몰핀에서 모두 현격한 증가를 나타내었다. 3 봉독과 몰핀주입 30분후에 Bradykinin으로 동통유발 이후 LN은 봉독은 증가 몰핀은 현격한 감소를, HPL은 봉침은 증가 몰핀에서는 현격한 증가를, TFL은 봉침과 볼핀에서 모두 증가를 나타내었다. 결론 : 봉독은 Capsaicin 또는 Bradykinin으로 동통유발된 통각수용행동을 감소시키는 결과를 나타내었는데 이것은 기존의 연구결과들에서의 봉독의 항통각수용(통각억제성)의 효과를 입증하였고 봉약침은 염증의 개선이나 암과 관련된 동통에 유효한 방법임을 시사하는 것이다.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.481-491
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• 2023

The β subunits of high voltage-gated calcium channels (HGCCs) are essential for optimal channel functions such as channel gating, activation-inactivation kinetics, and trafficking to the membrane. In this study, we report for the first time the potent blood pressure-reducing effects of peptide fragments derived from the β subunits in anesthetized and non-anesthetized rats. Intravenous administration of 16-mer peptide fragments derived from the interacting regions of the β1 [cacb1(344-359)], β2 [cacb2(392-407)], β3 [cacb3(292-307)], and β4 [cacb4(333-348)] subunits with the main α-subunit of HGCC decreased arterial blood pressure in a dose-dependent manner for 5-8 min in anesthetized rats. In contrast, the peptides had no effect on the peak amplitudes of voltage-activated Ca²⁺ current upon their intracellular application into the acutely isolated trigeminal ganglion neurons. Further, a single mutated peptide of cacb1(344-359)-cacb1(344-359)_K357R-showed consistent and potent effects and was crippled by a two-amino acid-truncation at the N-terminal or C-terminal end. By conjugating palmitic acid with the second amino acid (lysine) of cacb1(344-359)_K357R (named K2-palm), we extended the blood pressure reduction to several hours without losing potency. This prolonged effect on the arterial blood pressure was also observed in non-anesthetized rats. On the other hand, the intrathecal administration of acetylated and amidated cacb1(344-359)_K357R peptide did not change acute nociceptive responses induced by the intradermal formalin injection in the plantar surface of rat hindpaw. Overall, these findings will be useful for developing antihypertensives.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.625-637
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• 1997

Calcium ions are implicated in a variety of physiological functions, including enzyme activity, membrane excitability, neurotransmitter release, and synaptic transmission, etc. Calcium antagonists have been known to be effective for the treatment of exertional angina and essential hypertension. Selective and nonselective voltage-dependent calcium channel blockers also have inhibitory action on the acute and tonic pain behaviors resulting from thermal stimulation, subcutaneous formalin injection and nerve injury. This study was undertaken to investigate the effects of iontophoretically applied $Ca^{++}$ and its antagonists on the responses of WDR (wide dynamic range) cells to sensory inputs. The responses of WDR cells to graded electrical stimulation of the afferent nerve and also to thermal stimulation of the receptive field were recorded before and after iontophoretical application of $Ca^{++}$, EGTA, $Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA, ${\omega}-conotoxin$ MVIIC and ${\omega}-agatoxin$ IVA. Also studied were the effects of a few calcium antagonists on the C-fiber responses of WDR cells sensitized by subcutaneous injection of mustard oil (10%). Calcium ions and calcium channel antagonists ($Mn^{++}$, verapamil, ${\omega}-conotoxin$ GVIA & ${\omega}-agatoxin$ IVA) current-dependently suppressed the C-fiber responses of WDR cells without any significant effects on the A-fiber responses. But ${\omega}-conotoxin$ MVIIC did not have any inhibitory actions on the responses of WDR cell to A-fiber, C-fiber and thermal stimulation. Iontophoretically applied EGTA augmented the WDR cell responses to C-fiber and thermal stimulations while spinal application of EGTA for about $20{\sim}30\;min$ strongly inhibited the C-fiber responses. The augmenting and the inhibitory actions of EGTA were blocked by calcium ions. The WDR cell responses to thermal stimulation of the receptive field were reduced by iontophoretical application of $Ca^{++}$, verapamil, ${\omega}-agatoxin$ IVA, and ${\omega}-conotoxin$ GVIA but not by ${\omega}-conotoxin$ MVIIC. The responses of WDR cells to C-fiber stimulation were augmented after subcutaneous injection of mustard oil (10%, 0.15 ml) into the receptive field and these sensitized C-fiber responses were strongly suppressed by iontophoretically applied $Ca^{++}$, verapamil, ${\omega}-conotoxin$ GVIA and ${\omega}-agatoxin$ IVA. These experimental findings suggest that in the rat spinal cord, L-, N-, and P-type, but not Q-type, voltage-sensitive calcium channels are implicated in the calcium antagonist-induced inhibition of the normal and the sensitized responses of WDR cells to C-fiber and thermal stimulation, and that the suppressive effect of calcium and augmenting action of EGTA on WDR cell responses are due to changes in excitability of the cell.