Chronic inflammatory pain and chronic THC vapor inhalation alter midbrain neuronal activity

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.NEW & NOTEWORTHY 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.