• Advances in Traditional Medicine
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• v.6 no.4
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• pp.349-354
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• 2006

In the present study, three Malaysian Channa spp. fish Channa striatus, Channa micropeltes and Channa lucius were assessed for their analgesic activity. Distilled water and mixture of chloroform: methanol were used for extraction. The analgesic or antinociceptive activity was investigated by abdominal writhing and hot plate test. The water extract of Channa striatus and the chloroform: methanol extract Channa lucius produced potent antinociceptive effect when assessed with the abdominal writhing test. The activity was compared to morphine where the activity of the extracts was less potent than the opioid. In the hote plate test, water extract of Channa striatus revealed significant activity and chloroform:methanol extract of Channa micropeltes had moderate activity. However, these activities were statistically lower than morphine. Collectively, this study also showed that Channa striatus extract was more potent analgesic agent when compared to the other closely related snakehead Channa micropeltes and Channa lucius.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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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.

• Korean Journal of Acupuncture
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• v.26 no.2
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• pp.75-89
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• 2009

Objectives: Warm needling combines simultaneously the effects of acupuncture and moxibustion. This study was to investigate whether warm needling could relieve acute knee arthritis induced by carrageenan in rats. Methods: To illuminate the underlying mechanisms of the warm needling-induced antinociception, weight bearing force (WBF) was observed on the acute knee arthritic rat model. Under general anesthesia, ST36, SP9, Hakjung extra point, LI4 were punctured and stimulated with 30 mg moxa ball combustion on top of the needle (${\emptyset}0.18{\times}8mm$). Results: In behavioral test, rats subsequently showed a reduced stepping force of the affected limb 3 hours after the induction of arthritis. Warm needling on the contralateral or ipsilateral ST36 failed to show antinociceptive effect on the acute knee arthritis. Warm needling on the contralateral SP9 or LI4 increased WBF values to normal level in the acute stage of the arthritis. Warm needling on the Hakjung extra-point resulted in the significant antinociceptive effects through acute stage. These effects of warm needling were suppressed by opioids receptor antagonist naltrexone (10 mg/kg, i.p.) and alpha adrenoceptor antagonist phentolamine (5 mg/kg, i.p.). Conclusion: The data suggest that warm needling-induced antinociception is differently mediated by acupoints and accomplished by activating the descending inhibitory systems including endogenous opioids and $\alpha$-adrenoceptors.

• Molecules and Cells
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• v.42 no.2
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• pp.143-150
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• 2019

Chronic neuropathic pain is one of the primary causes of disability subsequent to spinal cord injury. Patients experiencing neuropathic pain after spinal cord injury suffer from poor quality of life, so complementary therapy is seriously needed. Dehydrocorybulbine is an alkaloid extracted from Corydalis yanhusuo. It effectively alleviates neuropathic pain. In the present study, we explored the effect of dehydrocorybulbine on neuropathic pain after spinal cord injury and delineated its possible mechanism. Experiments were performed in rats to evaluate the contribution of dehydrocorybulbine to P2X4 signaling in the modulation of pain-related behaviors and the levels of pronociceptive interleukins and proteins after spinal cord injury. In a rat contusion injury model, we confirmed that chronic neuropathic pain is present on day 7 after spinal cord injury and P2X4R expression is exacerbated after spinal cord injury. We also found that administration of dehydrocorybulbine by tail vein injection relieved pain behaviors in rat contusion injury models without affecting motor functions. The elevation in the levels of pronociceptive interleukins ($IL-1{\beta}$, IL-18, MMP-9) after spinal cord injury was mitigated by dehydrocorybulbine. Dehydrocorybulbine significantly mitigated the upregulation of P2X4 receptor and reduced ATP-evoked intracellular $Ca^{2+}$ concentration. Both P2XR and dopamine receptor2 agonists antagonized dehydrocorybulbine's antinociceptive effects. In conclusion, we propose that dehydrocorybulbine produces antinociceptive effects in spinal cord injury models by inhibiting P2X4R.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.133-137
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• 2005

Background: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55,212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55,212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55,212-2. Results: Intrathecal WIN 55,212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55,212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55,212-2. Conclusions: WIN 55,212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.

• The Korean Journal of Pain
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• v.20 no.2
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• pp.100-105
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• 2007

Background: Ginseng has been used to manage various types of pain in folk medicine. This study characterized the effect of treatment with intrathecal ginsenosides, the active components of ginseng in a postoperative pain model. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters. An incision was made in the plantar surface of the hindpaw. Withdrawal thresholds following the application of a von Frey filament to the wound site were measured. To determine the role of the opioid or GABA receptors following treatment with the ginsenosides, naloxone, bicuculline (a $GABA_A$ receptor antagonist), and saclofen (a $GABA_B$ receptor antagonist) were administered intrathecally 10 min before the delivery of the ginsenosides and the changes of the withdrawal thresholds after application of the von Frey filament were Observed. Results: Treatment with the intrathecal ginsenosides increased the withdrawal threshold in a dose dependent manner. Pre-treatment with intrathecal naloxone reversed the antinociceptive effect of the ginsenosides. However, pre-treatment with intrathecal bicuculline and saclofen failed to have an effect on the activity of the ginsenosides. Conclusions: These results suggest that ginsenosides are effective to alleviate the postoperative pain evoked by paw incision. The opioid receptor, but not GABA receptors, may be involved in the antinociceptive action of the ginsenosides at the spinal level.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.97-105
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• 2022

Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

• Journal of Ginseng Research
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• v.29 no.2
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• pp.94-99
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• 2005

In the previous study, we reported that the in viかo inhibitory effect of ginsenosides, active ingredient of Panax ginseng, on $5-HT_{3A}$ receptor channel activity is coupled to in vivo anti-vomiting and anti-nausea effect. In the present study, we further investigated that the inhibitory effect of ginsenosides, active ingredient of Panax ginseng, on 5-HT3A receptor channel activity is also coupled to attenuation of irritable bowel syndrome (IBS), which is induced by colorectal distention (CRD) and $0.6\%$ acetic acid treatment. The CRD-induced visceral pains induced by CRD and acetic acid treatment are measured by frequency of contractions of the external oblique muscle in conscious rats. Treatment of GTS significantly inhibited CRD-induced visceral pain with dose-dependent manner. The $EC_{50}$ was $5.5{\pm}4.7$ mg/kg ($95\%$ confidence intervals: 1.2-15.7) and the antinociceptive effect of GTS on visceral pain was persistent for 4 h. We also compared the effects of protopanaxadiol (PD) ginsenosides and protopanaxatriol (PT) ginsenosides with saline on acetic acid-and CRD-induced visceral pain, and found that protopanaxatriol (PT) ginsenosides was much more potent than PD ginsenosides in attenuating CRD-induced visceral pain. These results indicate that U ginsenosides of Panax ginseng are components far attenuation of experimentally CRD-induced visceral pains.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.143-146
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• 2003

Triterpenoids, ursolic acid (1) and 23-hydroxyursolic acid (2) were obtained from the hydrolysis of BuOH fraction of Cussonia bancoensis extract to test anti nociceptive and anti-inflammatory effect of C. bancoensis (Araliaceae). Compound 1 and 2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. The effect of 2 was much more potent in acetic acid-induced writhing test than in hot plate test. Compound 1 and 2 significantly inhibited 1％-carrageenan-induced edema in the rat. These results suggest that the two triterpenes, ursolic acid and 23-hydroxyursolic acid, are responsible for the antinociceptive and anti-inflammatory effect of C. bancoesnsis.

• IMMUNE NETWORK
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• v.22 no.4
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• pp.34.1-34.19
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• 2022

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)₂D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.