Dopamine D1 And D2 receptors mediate analgesic and hypnotic effects of L-Tetrahydropalmatine in a mouse neuropathic pain model

Liu, Y.-Y.; Wang, T.-X.; Zhou, Jianyu; Qu, Wei‐Min; Huang, Zhi‐Li

doi:10.1016/j.sleep.2019.11.448

Cited by 7 publications

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“…Previous studies have shown that THP mediates analgesia by blocking D1/2 dopamine receptors in the striatum and hypothalamic arcuate nucleus, thus activating the descending antinociceptive system from the periaqueductal gray to the spinal dorsal horn and inhibiting nociceptive signal transduction. 10 , 32 Few studies have shown the role of THP in the spinal cord, but the spinal cord is the main central system of pain. Therefore, this study addresses the analgesic effect of THP at the level of spinal cord tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Tetrahydropalmatine (THP), an active component of traditional Chinese herbs derived from the corydalis Yanhusuo, has been reported to possess anti‐inflammatory and antinociceptive effects. 10 , 11 Although THP is a traditional analgesic medicine in the clinic, the mechanism of its antinociceptive effect is still unclear. Whether this traditional analgesic can attenuate the regulation of glial cell activation and apoptosis is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

et al. 2021

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Background Pain is an unpleasant sensory experience that usually plays a protective role. Inflammatory pain is often severe and stubborn, which has a great impact on the quality of life of patients. However, there has been no breakthrough in the treatment strategy and mechanism of inflammatory pain. Methods This study investigated the analgesic effect of tetrahydropalmatine (THP) in rats injected with complete Freund's adjuvant (CFA)-induced inflammatory pain. Allodynia and gait analysis of rats were used to evaluate the analgesic effect at different time points before and after operation. THP (2.5, 5, and 10 mg/kg) was administered intraperitoneally once daily for 7 days post Day 3. The expression levels of TNF- α and IL-1 β in the spinal cord were measured by enzyme-linked immunosorbent assay. The activation of astrocytes and microglial cells in the spinal cord was tested by western blot before and after THP treatment. The apoptosis of glial cells was tested by flow cytometry after treatment with THP in the primary cultured glial cell model. Results CFA treatment induced significant allodynia and caused abnormal gait in rats. Administration of THP at 10 mg/kg significantly alleviated CFA-induced inflammatory pain behaviors. Moreover, CFA-induced activation of glial cells and the increased levels of TNF- α and IL-1 β were inhibited by THP administration. In addition, THP promotes apoptosis in primary cultured glial cells. This study suggests the possible clinical utility of THP in the treatment of inflammatory pain. Conclusion THP plays an analgesic role by inhibiting the activation of glial cells and promoting apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

et al. 2021

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“…In addition, it has been reported that the antinociceptive effects of the natural compound dehydrocorybulbine (DHCB) can be reversed by a D2DR agonist, as determined by the tail-flick assay, and that DHCB cannot alleviate pain in D2DR KO mice 41 . A clinical drug, rotundine, was also found to alleviate neuropathic pain through agonism of D1DR and antagonism of D2DR 42 . The different effects of dopamine receptor agonists and antagonists on pain observed in these studies might have been due to the use of different models and methods for measuring pain, but the main problem might be that the mechanisms by which D1DR and D2DR are involved in regulating pain still need to be explored.…”

Section: Discussionmentioning

confidence: 99%

The dopamine D1–D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

et al. 2021

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Dopamine D1 receptor (D1DR) and D2 receptor (D2DR) are closely associated with pain modulation, but their exact effects on neuropathic pain and the underlying mechanisms remain to be identified. Our research revealed that intrathecal administration of D1DR and D2DR antagonists inhibited D1–D2DR complex formation and ameliorated mechanical and thermal hypersensitivity in chronic constriction injury (CCI) rats. The D1–D2DR complex was formed in the rat spinal cord, and the antinociceptive effects of D1DR and D2DR antagonists could be reversed by D1DR, D2DR, and D1–D2DR agonists. Gαq, PLC, and IP3 inhibitors also alleviated CCI-induced neuropathic pain. D1DR, D2DR, and D1–D2DR complex agonists all increased the intracellular calcium concentration in primary cultured spinal neurons, and this increase could be reversed by D1DR, D2DR antagonists and Gαq, IP3, PLC inhibitors. D1DR and D2DR antagonists significantly reduced the expression of p-PKC γ, p-CaMKII, p-CREB, and p-MAPKs. Levo-corydalmine (l-CDL), a monomeric compound in Corydalis yanhusuo W.T. Wang, was found to obviously suppress the formation of the spinal D1–D2DR complex to alleviate neuropathic pain in CCI rats and to decrease the intracellular calcium concentration in spinal neurons. l-CDL-induced inhibition of p-PKC γ, p-MAPKs, p-CREB, and p-CaMKII was also reversed by D1DR, D2DR, and D1–D2DR complex agonists. In conclusion, these results indicate that D1DR and D2DR form a complex and in turn couple with the Gαq protein to increase neuronal excitability via PKC γ, CaMKII, MAPK, and CREB signaling in the spinal cords of CCI rats; thus, they may serve as potential drug targets for neuropathic pain therapy.

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“…Owing to its wide range of pharmacological activities, C. yanhusuo has been used as a tonic for treating pain [15], insomnia [16], drug addiction [17], and hypertension [18]. In TCM, processed C. yanhusuo is believed to have superior pharmacological efficacy compared with raw C. yanhusuo.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Processing and Compatibility of Corydalis yanhusuo: Phytochemistry, Pharmacology, Pharmacokinetics, and Safety

Yang

Mao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Processed and polyherbal formulations (compatibility) are widely used in traditional Chinese medicine (TCM). However, processing and compatibility may alter the efficacy and safety of herbal medicines, and therefore, evaluating the herbal medicines changes after processing and compatibility is important for their safety. Since Corydalis yanhusuo (Y.H.Chou & Chun C.Hsu) W.T.Wang ex Z.Y.Su & C.Y.Wu (Family: Papaveraceae and Genera: Corydalis), a traditional medicinal plant in China, Japan, Korea, and other Asian countries, has been used for treating a wide range of medical conditions, it is an ideal representative of studying the effects of processing and compatibility on efficacy and toxicity. In this paper, information was obtained by searching electronic databases, classic books, PhD and MSc dissertations, local conference papers, and unpublished materials prior to July 2021. We provide a summary of the phytochemistry, pharmacology, pharmacokinetics, quality control, and safety of C. yanhusuo under various processing or compatibility conditions. Based on our findings, vinegar processing is probably the best C. yanhusuo processing method, which could increase the absorption rate of tetrahydropalmatine (THP) in the heart, liver, spleen, lung, and brain tissues and alleviate mice muscle tremors and liver damage caused by C. yanhusuo. These results indicate that processing and compatibility can reduce toxicity and increase the efficacy of C. yanhusuo. The information provides an expanded understanding of the efficacy and toxicity mechanisms of TCM compounds, which is valuable for industrial production quality control and future drug research.

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Dopamine D1 And D2 receptors mediate analgesic and hypnotic effects of L-Tetrahydropalmatine in a mouse neuropathic pain model

Cited by 7 publications

References 0 publications

Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

Tetrahydropalmatine exerts analgesic effects by promoting apoptosis and inhibiting the activation of glial cells in rats with inflammatory pain

The dopamine D1–D2DR complex in the rat spinal cord promotes neuropathic pain by increasing neuronal excitability after chronic constriction injury

Processing and Compatibility of Corydalis yanhusuo: Phytochemistry, Pharmacology, Pharmacokinetics, and Safety

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