Electrical Stimulation of the Ventral Lateral Periaqueductal Gray Induces Antinociception in Rats

Despite the central role of general anesthesia in modern healthcare, the frequency of anesthesia-related morbidity resulting from the toxicity and non-specificity of anesthetic drugs remains high. Among the key behavioral states of general anesthesia is antinociception (reduced sensitivity to pain). Within the nociceptive pathway in the brain and the central nervous system, the periaqueductal gray (PAG) has been shown to be a key site that modulates antinociception responses. We hypothesize that electrical stimulation of the ventral lateral periaqueductal gray (vIPAG) in rodents reliably induces antinociception in a physiology-derived way. Rectangular electrical stimuli were applied at the vlPAG of rats at animal-specific optimal currents. We found that antinociception levels increased by 85% [69%-102%] (mean, [95% Cl]) at the 10-minute time points of 1-hour stimulations in 18 experiments across 6 animals. Antinociception neither increased nor decreased significantly over the course of the stimulation. The levels of antinociception decayed back to baseline ranges within 26 [22-31] (mean, [95% Cl]) minutes after stimulation. Our findings suggest a promising step towards the design of behavioral states in general anesthesia by manipulating directly one of the brain's natural nociceptive pathways, in addition to or in place of the current pharmacology-based anesthesiology procedures.