• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.211-214
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• 1997

In the present study, we investigated the mechanisms of antinociceptive effect and thermoregulatory action of capsaicin in guinea pigs. The administration of capsaicin (5 mg/kg, s.c.) caused a significant decrease in frequency of eye wiping, an indicative of nociceptive threshold. This antinociceptive effect of calsaicin was abolished by co-administration of capsazepine (30 mg/kg, s.c.) with capsaicin, suggesting the involvement of a vanilloid receptor in the antinociceptive action of capsaicin. The administration of capsaicin (1 mg/kg, s.c.) produced a significant decrease in body temperature of guinea pigs. The maximum decrease in body temperature by 2 degrees was shown 1 hour after the treatment, and this decrease was not reversed by coadministration of capsazepine. In conclusion, it is suggested that the mechanism of action of capsaicin-induced thermoregulation involves different pathways from that of capsaicin-induced antinociception.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.142.2-143
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• 2000

• Bulletin of the Korean Chemical Society
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• v.31 no.6
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• pp.1501-1505
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• 2010

We report design and synthesis of the novel TRPV1 ligands through a rational approach. Simplified analogues of 12(S)-HPETE showing TRPV1 agonistic effect are disclosed. Biological evaluation revealed that substitution of functional groups without any change in conformation converted agonist into antagonist. Our work provided key information with regard to TRPV1 agonist/antagonist switching.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.244.1-244.1
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• 2003

Advances in understanding of pain and analgesia have been made. Over the past few years, we have designed and synthesized a series of VR agonists, based on the structures of 12-HPETE and capsaicin. the natural VR agonist. But for the development of analgesic drugs, these synthetic VR agonists had problems like burning sensation. hypothermia. etc. So our recent studoes have focused on designs and syntheses of VR antagonists based on the structure of capsaicin(natural VR agonist), and capsazepine(synthetic VR antagonist). (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.349.1-349.1
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• 2002

Capsaicin. the pungent component of chili pepper. opens a novel cation selective ion channel in the plasma membrane of peripheral sensory neurons. Capsaicin channel agonists induce pain upon topical application in the early stage. which is followed by a period of desensitization. Although the agonists have been studied as a analgesics, their initial irritancy became sever side effect. So competive antagonists have been pursued as a novel pharmacological agent for analgesics, rather than agonists. (omitted)

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.328-333
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• 2022

Repeated morphine administration induces tolerance to its analgesic effects. A previous study reported that repeated morphine treatment activates transient receptor potential vanilloid type 1 (TRPV1) expression in the sciatic nerve, dorsal root ganglion, and spinal cord, contributing to morphine tolerance. In the present study, we analyzed TRPV1 expression and binding sites in supraspinal pain pathways in morphine-tolerant mice. The TRPV1 mRNA levels and binding sites were remarkably increased in the cortex and thalamus of these animals. Our data provide additional insights into the effects of morphine on TRPV1 in the brain and suggest that changes in the expression of, and binding to TRPV1 in the brain are involved in morphine tolerance.

• The Korean Journal of Pain
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• v.37 no.4
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• pp.288-298
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• 2024

Nerve growth factor (NGF) is a neurotrophic protein that has crucial roles in survival, growth and differentiation. It is expressed in neuronal and non-neuronal tissues. NGF exerts its effects via two types of receptors including the high affinity receptor, tropomyosin receptor kinase A and the low affinity receptor p75 neurotrophin receptor highlighting the complex signaling pathways that underlie the roles of NGF. In pain perception and transmission, multiple studies shed light on the effects of NGF on different types of pain including inflammatory, neuropathic, cancer and visceral pain. Also, the binding of NGF to its receptors increases the availability of many nociceptive receptors such as transient receptor potential vanilloid 1, transient receptor potential ankyrin 1, N-methyl-D-aspartic acid, and P2X purinoceptor 3 as well as nociceptive transmitters such as substance P and calcitonin gene-related peptide. The role of NGF in pain has been documented in pre-clinical and clinical studies. This review aims to shed light on the role of NGF and its signaling in different types of pain.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.309-316
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• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• The Journal of Korean Physical Therapy
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• v.22 no.3
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• pp.71-77
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• 2010

Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.

• Journal of Korean Neurosurgical Society
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• v.42 no.6
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• pp.462-469
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• 2007

Objective : This study characterized the neurons in the lumbosacral cord that express phospho ERK (pERK) after distension or irritation of the bladder, and their relation to the vanilloid receptor 1 (VR1) positive primary afferents. Methods : Mechanical distension and chemical irritation of the bladder were induced by intravesical injection of the saline and mustard oil, respectively. Spinal neurons expressing pERK and the primary afferent fibers were characterized using multiple immunofluorescence for neurokinin 1 (NK1), neuronal nitric oxide synthetase (nNOS) and VR1. Results : Neurons in lamina I, medial dorsal horn (MDH), dorsal gray commissure (DGC) and sacral parasympathetic nucleus (SPN) were immunoreactive for pERK after either mechanical or chemical stimulation. The majority of pERK positive cells were positive for NK1 in lamina I and SPN, but not in the DGC. Most of pERK positive cells are not stained for nNOS except in a small population of the cells in the SPN and DGC. Contacts between perikarya and dendrites of pERK-positive cells and terminals of primary afferents expressing VR1 were identified in lamina I. lateral collateral path (LCP) and SPN. Conclusion : In this study, the lumbosacral neurons activated by mechanical and chemical stimulation of the urinary bladder were identified with expression of the pERK, and also provided the evidence that VR1-positive primary afferents may mediate the activation of these neurons.