Analgesic effects of co-administration of mirogabalin and diclofenac sodium on neuropathic pain in rats

被引：1

作者：

Chikubu, Hiroto ^{[1
,2
]}

Inage, Kazuhide ^{[1
]}

Orita, Sumihisa ^{[1
,3
]}

Shiga, Yasuhiro ^{[1
]}

Inoue, Masahiro ^{[1
]}

Shimizu, Keisuke ^{[4
]}

Suzuki-Narita, Miyako ^{[5
]}

Tajiri, Ikuko ^{[1
]}

Mukai, Michiaki ^{[1
]}

Nozaki-Taguchi, Natsuko ^{[2
]}

Ohtori, Seiji ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, 1-8-1 Inohana Chuo Ku, Chiba, Chiba 2608670, Japan

[2] Chiba Univ, Grad Sch Med, Dept Anesthesiol, Chiba, Japan

[3] Chiba Univ, Ctr Frontier Med Engn, Chiba, Japan

[4] Chiba Univ, Future Med Educ & Res Org, Chiba, Japan

[5] Chiba Univ, Grad Sch Med, Dept Bioenvironm Med, Chiba, Japan

来源：

JOURNAL OF ORTHOPAEDIC RESEARCH | 2025年 / 43卷 / 01期

关键词：

analgesia; chronic constriction injury rat model; diclofenac sodium; mirogabalin; neuropathic pain; CHRONIC CONSTRICTION INJURY; SPINAL SUBNUCLEUS CAUDALIS; WEIGHT-BEARING; TACTILE ALLODYNIA; UP-REGULATION; MICROGLIA; MECHANISMS; NERVE; MODEL; HYPERALGESIA;

D O I：

10.1002/jor.25977

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

Co-administration of mirogabalin besylate and nonsteroidal anti-inflammatory drugs is effective for neuropathic pain; however, mechanism of its action remains unknown. We aimed to evaluate the mechanism of this synergistic effect of the concomitant administration for neuropathic pain using chronic constriction injury model rats. Fifty male Wister rats of 7-week-old were used. Right sciatic nerve ligation was performed in 40 rats and they were sub-divided into four groups: vehicle, mirogabalin, diclofenac sodium and co-administration of them. Ten rats underwent sham surgery. Fluorogold was attached to sciatic nerve during surgery. Von Frey filament and weight bearing tests were performed on postoperative Day 6 as behavioral assessments and drug was administrated intraperitoneally. Half rats in each group underwent behavioral assessment and perfusion fixation using 4% paraformaldehyde on postoperative Day 7 and remaining on postoperative Day 14. Subsequently, dorsal root ganglion at L4 to L6 was collected and examined immunohistochemistry for calcitonin gene-related peptide, and their immunoreactivity in fluorogold-labeled neurons was measured. Spinal cord at lumbar swelling was resected, immunostained for ionized-calcium-binding adapter molecule-1 and glial fibrillary acidic protein, and immunoreactive neurons in dorsal horn of spinal cords were calculated as the occupancy of them. Mirogabalin suppresses the neuropeptide-release from presynaptic afferent neuron directly and it resulted in suppressing glia cells activation. Diclofenac sodium inhibits cyclooxygenase-2 and prostaglandin production, related to allodynia. These effects of mirogabalin and diclofenac sodium, respectively, inhibited glia cells strongly, which is presumed to be one of the mechanisms for the effectiveness of their co-administration for neuropathic pain.

引用

页码：200 / 209

页数：10

共 48 条

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