Kelley Leslie K, Gilpin Nicholas W, Middleton Jason W
Department of Physiology, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, Louisiana, United States.
Alcohol and Drug of Abuse Center of Excellence, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, Louisiana, United States.
J Neurophysiol. 2025 Jul 1;134(1):80-93. doi: 10.1152/jn.00456.2024. Epub 2025 May 14.
In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically in neurons that respond to current input with a "delayed" firing phenotype. Treatment with CFA led to increased firing rate and increased spontaneous inhibitory postsynaptic current (sIPSC) amplitude in vlPAG neurons of female rats, and chronic THC vapor rescued sIPSC amplitudes to control levels-these effects in females were specific to vlPAG neurons categorized as having an "onset" firing phenotype. Ongoing work is exploring sex-specific mechanisms and cell types involved in THC vapor inhalation effects on vlPAG neurons in rats treated with CFA, and determining the role of these changes in THC vapor inhalation effects on pain-related behavior. Many in the United States with pain self-medicate with delta-9 tetrahydrocannabinol (THC) and cannabis, and many humans use e-cigarette-type devices filled with cannabis extracts to self-administer THC. Until recently, most rodent studies have used injection procedures and male rats. Chronic THC vapor reduced synaptic inhibition and neural firing in ventrolateral periaqueductal gray (vlPAG) neurons in males and rescued chronic inflammatory pain-induced increase in synaptic inhibition in females.
为了减少临床上治疗疼痛对阿片类药物的依赖，正在进行的研究正在测试大麻素药物作为治疗慢性疼痛潜在替代品的效用。我们测试了慢性δ-9四氢大麻酚（THC）蒸汽吸入对用完全弗氏佐剂（CFA）处理的雄性和雌性大鼠腹外侧导水管周围灰质（vlPAG）神经元的内在特性和突触特性的影响。我们报告称，慢性THC蒸汽吸入可调节vlPAG神经元的内在特性和突触特性，包括雄性大鼠动作电位发放率降低和自发性抑制性突触传递减少，并且这些影响特别发生在对当前输入以“延迟”发放表型做出反应的神经元中。CFA处理导致雌性大鼠vlPAG神经元的发放率增加和自发性抑制性突触后电流（sIPSC）幅度增加，而慢性THC蒸汽将sIPSC幅度恢复到对照水平——雌性大鼠中的这些影响特定于归类为具有“起始”发放表型的vlPAG神经元。正在进行的研究正在探索CFA处理的大鼠中THC蒸汽吸入对vlPAG神经元影响所涉及的性别特异性机制和细胞类型，并确定这些变化在THC蒸汽吸入对疼痛相关行为影响中的作用。在美国，许多疼痛患者自行使用δ-9四氢大麻酚（THC）和大麻进行自我治疗，许多人使用装有大麻提取物的电子烟型设备自行服用THC。直到最近，大多数啮齿动物研究都使用注射方法且以雄性大鼠为研究对象。慢性THC蒸汽减少了雄性大鼠腹外侧导水管周围灰质（vlPAG）神经元的突触抑制和神经发放，并挽救了雌性大鼠慢性炎症性疼痛引起的突触抑制增加。
