• 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.

• Natural Product Sciences
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• v.25 no.1
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• pp.64-71
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• 2019

The present study was conducted to investigate anti-nociceptive and anti-inflammatory effects of the leaves of Ilex latifolia Thunb (I. latifolia) in in vivo and in vitro. Writhing responses induced by acetic acid and formalin- and thermal stimuli (tail flick and hot plate tests)-induced pain responses for nociception were evaluated in mice. I. latifolia (50 - 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), inhibited the acetic acid-induced writhing response and the second phase response (peripheral inflammatory response) in the formalin test, but did not protect against thermal nociception and the first phase response (central response) in the formalin test. These results show that I. latifolia has a significant anti-nociceptive effect that appears to be peripheral, but not central. Additionally, I. latifolia (50 and $100{\mu}g/mL$) and 3,5-di-caffeoyl quinic acid methyl ester ($5{\mu}M$) isolated from I. latifolia as an active compound significantly inhibited LPS-induced NO production and mRNA expression of the pro-inflammatory mediators, iNOS and COX-2, and the pro-inflammatory cytokines, IL-6 and $IL-1{\beta}$, in RAW 264.7 macrophages. These results suggest that I. latifolia can produce antinociceptive effects peripherally, but not centrally, via anti-inflammatory activity and supports a possible use of I. latifolia to treat pain and inflammation.

• The Korean Journal of Pain
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• v.36 no.2
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• pp.163-172
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• 2023

Background: Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. Methods: Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. Results: Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. Conclusions: This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

• Korean Journal of Pharmacognosy
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• v.51 no.3
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• pp.186-191
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• 2020

In this study, we evaluated the anti-nociceptive activities of Sorbus alnifolia. To investigate the anti-nociceptive properties of the methanolic extract of Sorbus alnifolia (MSA), we conducted several tests using various experimental mouse pain models. Herein, MSA significantly delayed the latency time and writhing motion in the hotplate test and acetic acid test, respectively. These result indicated that MSA has an ability to manage both peripheral and central nociception. We could further confirm the analgesic effects of MSA by performing formalin test. In combination test using naloxone, a non-selective opioid receptor antagonist, analgesic activity of MSA was partly antagonized by naloxone, but not completely, indicating that the MSA acts as a partial opioid receptor agonist. Out results suggest that the S. alnifolia may be possibly used as valuable anti-nociceptive agent.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.323-327
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• 2006

Despite the wealth of data concerning the roles of ${\alpha}-CGRP$ in nociceptive behaviors, ${\alpha}-CGRP-null$ mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that ${\alpha}-CGRP$ null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that ${\alpha}-CGRP$ is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

• Korean Journal of Plant Resources
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• v.20 no.3
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• pp.226-233
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• 2007

To develop a clinically available saponin- or sapogenin complex from Oriental medicines, the EtOH extract (KPRG-A) was obtained by extracting from the four crude drugs, Kalopanacis Cortex, Platycodi Radix, Rubi Fructus and Glycyrrhizae Radis. The BuOH fraction (KPRG-B), a crude saponin complex, was prepared by fractionating KPRG-A, which were further completely hydrolyzed to afford the sapogenin complex (KPRG-D). In an attempt to find the antinoicpetive effects of the saponin complex and sapogenin complex, KPRG-C, and -D, were assayed by writhing-, hot plate-, and tail-flick tests using mice or rats. The three samples were also subjected to antiiflammatory tests using serotonin-induced and carrageenan-induced hind paw edema mice and rats, respectively. The three samples significantly reduced inflammations and pains of the experimental animal. The potency were found in the order of KPRG-D> KPRG-C> KPRG-B. The most active sample, KPRG-D, caused no death, no body increase or no anatomical pathlogic change even at 2,000 mg/kg dose. These results suggest that a sapogenin complex, KPRG-D, which was found to contain mainly hederagenin, platycodigenin, polygalacic acid, 23-hydroxytormentic acid, glycyrrhetic acid together with minor triterpene acids, could be a potential candidate for antiinflammatory therapeutics.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.1
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• pp.53-60
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• 2002

Neurosensory dysfunction of the injured inferior alveolarnerve(IAN) is a common and distrssing consequence of traumatic or iatrogenic injury. Conventional neurosensory testing has been used to detect and monitor sensory impairments of the injured IAN. However, these tests had low reliability and are not qualitative at best because they are based on solely on the patient's subjective assesment of symptoms. Consequently, there is need for more reliable, sensitive, and objective test measures to document and to monitor sensory dysfunction of the trigeminal nerve. This study was to investigate DITI's (digital infrared thermographic imaging) potential as a diagnostic alternative for evaluating of the nerve injures and sensory disturbance. Subjects were 30 patients who had been referred to Ewha Medical Center due to sensory disturbance of the lower lip and chin followed after unobserved inferior alveolar nerve injuries. The patients were examined by clinical neurosensory tests as SLTD (static light touch discrimination), MDD (moving direction discrimination), PPN (pin prick nociception) and DITI (digital infrared thermographic imaging). The correlation between clinical sensory dysfunction scores(Sum of SLTD, MDD, PPN, NP, Tinel sign) and DITI were tested by Spearman nonparametric rank correlation anaylsis & Kruskal-Wallis test, Wilcoxon 2-sample test. This study resulted in as follows; (1) The difference of thermal difference between normal side and affected side was as ${\Delta}-3.2{\pm}0.13$. (2) The DITI differences of the subjects presenting dysesthesia of the lip and chin were correlated significantly with the neurosensory dysfunction scores(r=0.419, p=0.021)and SLTD (r=0.429, p<0.05). (3) The MDD, PPN, NP, Tinel sign, duration, gender were not correlated with DITI(p> 0.05). Therefore, the DITI(digital infrared thermographic imaging) can be an option of the useful objective diagnostic methods to evaluate the injured inferior alveolar nerve and sensory dysfunction of trigerminal nerve.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.3
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• pp.250-257
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• 2001

Sensory dysfunction following the injury of the inferior alveolar nerve requires objective examination to get a reproducible data and to provide necessary treatment. This study was designed to evaluate if the SEP(somatosensory evoked potentials) of the mental nerve can be used as an objective method for the diagnosis of nerve injury and sensory disturbances. The subjects were nineteen patients ($37.4{\pm}11.3$ years old) who had been suffered from sensory disturbance of the unilateral lower lip and mental region for over 6 months after the inferior alveolar nerve injuries confirmed by the microsurgical explorations. The clinical neurosensory tests as SLTD(static light touch discrimination), MDD(moving direction discrimination), 2PD(two point discrimination), PPN(pin prick nociception) and accompanied pain were preceded to electro-physiologic examinations as SEP. The score of sensory dysfunction (sum score of all sensory tests) ranged from 0 to 8 were compared to the latency differences of the mental nerve SEPs. The correlation between clinical sensory scores and SEPs were tested by Spearman nonparametric rank correlation analysis, the differences in SEP latency by Kruskal-Wallis test and the latency differences according to PPN and accompanied pain by Mann-Whitney U test. This study resulted that the difference of the latencies between normal side and affected side was $2.22{\pm}2.46$ msec and correlated significantly with the neurosensory dysfunction scores (p=0.0001). Conclusively, the somatosensory evoked potentials of the mental nerve can be a useful diagnostic method to evaluate the inferior alveolar nerve injuries and the change of sensory dysfunction to be reproduced as an objective assessment.