Bagher Amina M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Int J Mol Sci. 2025 May 7;26(9):4430. doi: 10.3390/ijms26094430.
Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes, characterized by mechanical allodynia, neuroinflammation, and oxidative stress. Current treatments offer limited efficacy and are often associated with systemic side effects. Emerging evidence suggests that activation of cannabinoid receptor type 2 (CB) may represent a promising target for managing neuropathic pain and inflammation. This study investigates the therapeutic potential of intraplantar β-Caryophyllene (BCP), a selective CB receptor agonist, administered as a topical intervention in a streptozotocin (STZ)-induced DPN mouse model. Hyperglycemia was induced by STZ injections, and diabetic mice received intraplantar BCP (9, 18, or 27 µg) daily for 21 days. Mechanical allodynia was assessed using von Frey filaments, and levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and oxidative stress markers (MDA, SOD, CAT) were quantified in hind paw tissues. BCP dose-dependently alleviated STZ-induced mechanical allodynia, with the 27 µg dose producing the most pronounced effect ( < 0.001). The anti-allodynic effects of BCP were mediated through CB receptor activation, confirmed by reversal with the CB antagonist AM630 ( < 0.001), while the CB antagonist AM251 had no significant impact. In addition, BCP significantly reduced pro-inflammatory cytokines ( < 0.01) and oxidative stress markers ( < 0.001) while restoring antioxidant enzyme activities ( < 0.05). A control group treated with a clinically available topical analgesic cream containing capsaicin 0.075% exhibited limited efficacy. These findings position topical BCP administration as a novel therapeutic strategy for DPN, offering sustained pain relief and modulation of neuroinflammatory and oxidative pathways with minimal systemic exposure. Further clinical studies are warranted to validate its potential for translation into therapeutic practice.
糖尿病周围神经病变（DPN）是糖尿病一种使人衰弱的并发症，其特征为机械性异常性疼痛、神经炎症和氧化应激。目前的治疗方法疗效有限，且常伴有全身性副作用。新出现的证据表明，激活2型大麻素受体（CB）可能是治疗神经性疼痛和炎症的一个有前景的靶点。本研究调查了在链脲佐菌素（STZ）诱导的DPN小鼠模型中，作为局部干预给药的足底内β-石竹烯（BCP）（一种选择性CB受体激动剂）的治疗潜力。通过注射STZ诱导高血糖，糖尿病小鼠每天接受足底内BCP（9、18或27μg），持续21天。使用von Frey细丝评估机械性异常性疼痛，并对后爪组织中促炎细胞因子（TNF-α、IL-1β、IL-6）和氧化应激标志物（MDA、SOD、CAT）的水平进行定量。BCP剂量依赖性地减轻了STZ诱导的机械性异常性疼痛，27μg剂量产生的效果最显著（<0.001）。BCP的抗异常性疼痛作用是通过CB受体激活介导的，CB拮抗剂AM630可逆转此作用（<0.001），而CB拮抗剂AM251则无显著影响。此外，BCP显著降低了促炎细胞因子（<0.01）和氧化应激标志物（<0.001），同时恢复了抗氧化酶活性（<0.05）。用含0.075%辣椒素的市售局部镇痛乳膏治疗的对照组疗效有限。这些发现表明局部给予BCP是DPN的一种新治疗策略，可提供持续的疼痛缓解，并以最小的全身暴露调节神经炎症和氧化途径。有必要进行进一步的临床研究，以验证其转化为治疗实践的潜力。
