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1.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 30-41, 2023.
Artículo en Chino | WPRIM | ID: wpr-998160

RESUMEN

ObjectiveTo investigate the analgesic effect and mechanism of Osteoking (OK) on nerve compression in lumbar disc herniation. MethodThe rat model of chronic compression of dorsal root ganglion (CCD) was established to simulate clinical lumbar disc herniation. The CCD rats were randomly divided into model group, low, medium, and high dose OK groups (1.31, 2.63, 5.25 mL·kg-1·d-1), and pregabalin group (5 mg·kg-1), with eight rats in each group. Another eight SD rats were taken as the blank group, and the same volume of normal saline was given by gavage. Behavioral tests, side effect evaluation, network analysis, Western blot, immunofluorescence, and antagonist application were used to explore the effect. ResultCompared with the blank group, the mechanical hyperalgesia threshold, thermal hyperalgesia threshold, and the expression of inflammatory factors in the spinal dorsal horn of the model group are significantly increased (P<0.01), and the related indicators of the affected foot footprints are significantly down-regulated (P<0.01). The expression of signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor A (VEGFA), and phosphorylated extracellular regulated protein kinase (p-ERK) in microglia in the spinal dorsal horn is significantly increased in the model group (P<0.01). Compared with the model group, low, medium, and high dose OK groups can increase the mechanical hyperalgesia and thermal hyperalgesia thresholds of CCD rats (P<0.05, P<0.01) in a dose-dependent manner, improve the gait of CCD rats (P<0.05, P<0.01), and reduce the expression of inflammatory factors in the spinal dorsal horn (P<0.05, P<0.01). The expression of STAT3, VEGFA, and p-ERK in the spinal dorsal horn microglia of CCD rats is significantly decreased (P<0.05, P<0.01), and the acetic acid-induced nociceptive response in rats is effectively reduced (P<0.05, P<0.01). In addition, there is no tolerance. The results of the body mass test, organ index, forced swimming, and rotation show that OK has no obvious toxic or side effects. Further antagonist experiments show that MRS1523 and RS127445 can reverse the transient analgesic effect of OK compared with the high dose OK group (P<0.01). ConclusionOK has a good analgesic effect on the CCD model without obvious toxic side effects, and its mechanism may be related to the activation of ADORA3 and HTR2B and the inhibition of STAT3, VEGFA, p-ERK, and other elements in microglia.

2.
The Korean Journal of Pain ; : 22-32, 2006.
Artículo en Coreano | WPRIM | ID: wpr-200723

RESUMEN

BACKGROUND: This study was conducted to investigate the roles of the spinal and peripheral gamma-aminobutyric acid (GABA)-ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). METHODS: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. RESULTS: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. CONCLUSIONS: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.


Asunto(s)
Animales , Ratas , Dolor de Espalda , Baclofeno , Bicuculina , Agonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-A , Agonistas de Receptores GABA-B , Ácido gamma-Aminobutírico , Ganglios Espinales , Hiperalgesia , Hipersensibilidad , Muscimol , Neuralgia , Células del Asta Posterior , Receptores de GABA , Médula Espinal
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