镰状细胞病(SCD)患者经常经历慢性疼痛以及不可预测的急性疼痛发作,这极大地影响了他们的生活质量和预期寿命。目前SCD相关疼痛的治疗策略主要依赖于阿片类镇痛药,疗效有限,并引起严重的不良反应。大麻已经成为一种潜在的替代品,但其疗效仍不确定。在这项研究中,我们研究了Δ9-四氢大麻酚(THC)的抗伤害作用,大麻令人陶醉的成分,在雄性HbSS小鼠中,表达>99%的人类镰刀血红蛋白,和雄性HbAA小鼠,它表达正常的人类血红蛋白A,作为一个控制。急性THC给药(0.1-3mg-kg-1,腹膜内,i.p.)剂量依赖性地降低HbSS的机械和冷超敏反应,但不是HbAA小鼠。在甩尾试验中,THC(1和3mg-kg-1,腹膜内)在HbSS小鼠中产生了实质性的抗伤害作用。相比之下,THC(1mg-kg-1,i.p.)不会改变焦虑样行为(升高加迷宫)或长期记忆(24小时新颖物体识别)。亚慢性THC治疗(1和3mg-kg-1,i.p.)可持续缓解机械超敏反应,但导致HbSS小鼠对冷超敏反应的耐受性。一起,本研究发现THC是治疗SCD慢性疼痛的一种可能选择.需要进一步研究以阐明其作用机制以及与其他大麻成分的可能相互作用。意义声明该研究使用人源化小鼠模型探索了THC在缓解镰状细胞病(SCD)中的疼痛中的功效。研究结果表明,急性THC可降低SCD小鼠的机械和冷超敏反应,而不会影响情绪和认知功能障碍。亚慢性THC治疗可持续缓解机械性超敏反应,但会导致冷超敏反应耐受性。这些结果提供了对THC作为SCD替代疼痛管理选项的潜力的见解,强调它的优点和局限性。
People with sickle cell disease (SCD) often experience chronic pain as well as unpredictable episodes of acute pain, which significantly affect their quality of life and life expectancy. Current treatment strategies for SCD-associated pain primarily rely on opioid analgesics, which have limited efficacy and cause serious adverse effects. Cannabis has emerged as a potential alternative, yet its efficacy remains uncertain. In this study, we investigated the antinociceptive effects of Δ9-tetrahydrocannabinol (THC), cannabis\' intoxicating constituent, in male HbSS mice, which express >99% human sickle hemoglobin, and male HbAA mice, which express normal human hemoglobin A, as a control. Acute THC administration (0.1-3 mg-kg-1, intraperitoneal, i.p.) dose-dependently reduced mechanical and cold hypersensitivity in HbSS, but not HbAA mice. In the tail-flick assay, THC (1 and 3 mg-kg-1, i.p.) produced substantial antinociceptive effects in HbSS mice. By contrast, THC (1 mg-kg-1, i.p.) did not alter anxiety-like behavior (elevated plus maze) or long-term memory (24-h novel object recognition). Subchronic THC treatment (1 and 3 mg-kg-1, i.p.) provided sustained relief of mechanical hypersensitivity but led to tolerance in cold hypersensitivity in HbSS mice. Together, the findings identify THC as a possible therapeutic option for the management of chronic pain in SCD. Further research is warranted to elucidate its mechanism of action and possible interaction with other cannabis constituents. Significance Statement The study explores THC\'s efficacy in alleviating pain in sickle cell disease (SCD) using a humanized mouse model. Findings indicate that acute THC administration reduces mechanical and cold hypersensitivity in SCD mice without impacting emotional and cognitive dysfunction. Subchronic THC treatment offers sustained relief of mechanical hypersensitivity but leads to cold hypersensitivity tolerance. These results offer insights into THC\'s potential as an alternative pain management option in SCD, highlighting both its benefits and limitations.