Involvement of the Spinal Serotonergic System in the Analgesic Effect of [6]-Shogaol in Oxaliplatin-Induced Neuropathic Pain in Mice

Gang, Juan; Park, Keun-Tae; Kim, Suyong; Kim, Woojin

doi:10.3390/ph16101465

Cited by 3 publications

(2 citation statements)

References 53 publications

(120 reference statements)

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“…1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl) piperazine hydrobromide (NAN-190, 5-HT 1A receptor antagonist, 0.5, 2.5 µg/body; MedChemExpress, Monmouth Junction, NJ, USA) was dissolved in 10% dimethyl sulfoxide (DMSO, Wako Pure Chemicals, corp., Osaka, Japan) diluted with saline. The dose of NAN-190 utilized was selected based on previously studies [ 17 , 18 ].…”

Section: Methodsmentioning

confidence: 99%

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Kurita,

Sasaki,

Tanaka

et al. 2024

BMC Complement Med Ther

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Background Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. Methods A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. Results Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. Conclusion This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.

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Section: Methodsmentioning

confidence: 99%

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Kurita,

Sasaki,

Tanaka

et al. 2024

BMC Complement Med Ther

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“…Chemotherapy can cause peripheral neuropathic pain, leading to discontinuation or dose reduction [1]. Highly effective anticancer drugs, such as oxaliplatin, vincristine, cisplatin, and paclitaxel, can cause peripheral neuropathic pain [2,3]. Paclitaxel, discovered and isolated from Taxux brevifolia [4,5], is an anticancer drug used for breast, lung, and ovarian cancer [6].…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive Effect of Dendrobii caulis in Paclitaxel-Induced Neuropathic Pain in Mice

Park,

Jeon,

Kim

et al. 2023

Life

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Paclitaxel-induced neuropathic pain (PINP) is a serious adverse effect of chemotherapy. Dendrobii caulis (D. caulis) is a new food source used as herbal medicine in east Asia. We examined the antinociceptive effects of D. caulis extract on PINP and clarified the mechanism of action of transient receptor potential vanilloid 1 receptor (TRPV1) in the spinal cord. PINP was induced in male mice using multiple intraperitoneal injections of paclitaxel (total dose, 8 mg/kg). PINP was maintained from D10 to D21 when assessed for cold and mechanical allodynia. Oral administration of 300 and 500 mg/kg D. caulis relieved cold and mechanical allodynia. In addition, TRPV1 in the paclitaxel group showed increased gene and protein expression, whereas the D. caulis 300 and 500 mg/kg groups showed a significant decrease. Among various substances in D. caulis, vicenin-2 was quantified by high-performance liquid chromatography, and its administration (10 mg/kg, i.p.) showed antinociceptive effects similar to those of D. caulis 500 mg/kg. Administration of the TRPV1 antagonist capsazepine also showed antinociceptive effects similar to those of D. caulis, and D. caulis is thought to exhibit antinociceptive effects on PINP by modulating the spinal TRPV1.

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Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches

Cunha,

Tavares,

Costa-Pereira

2024

Brain Sciences

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Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy are starting to be unraveled, namely in the supraspinal pain modulatory system. Based on our interests and experience in the field, we undertook a review of the brain-centered alterations that may underpin pain in CIPN. The changes in the descending pain modulation in CIPN models along with the functional and connectivity abnormalities in the brain of CIPN patients are analyzed. A translational analysis of preclinical findings about descending pain regulation during CIPN is reviewed considering the main neurochemical systems (serotoninergic and noradrenergic) targeted in CIPN management in patients, namely by antidepressants. In conclusion, this review highlights the importance of studying supraspinal areas involved in descending pain modulation to understand the pathophysiology of CIPN, which will probably allow a more personalized and effective CIPN treatment in the future.

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Involvement of the Spinal Serotonergic System in the Analgesic Effect of [6]-Shogaol in Oxaliplatin-Induced Neuropathic Pain in Mice

Cited by 3 publications

References 53 publications

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study

Antinociceptive Effect of Dendrobii caulis in Paclitaxel-Induced Neuropathic Pain in Mice

Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches

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