Associative factors in tolerance to analgesia produced by electrical stimulation in the brainstem

Tolerance to the analgesic effects of electrical stimulation of the periaqueductal gray was confirmed, and it was demonstrated that this effect was mediated by environmental conditional stimuli (CSs). First, tolerance was extinguished after repeated presentation of CSs in the absence of brain stimulation. Second, environment-specific tolerance was demonstrated. Analgesia was reinstated after brain stimulation in a different test environment. Omission of brain stimulation in the stimulation environment failed to reveal a hyperalgesic response in tolerant Ss. Brain-stimulation analgesia should be beneficial for analyzing neural mechanisms underlying conditioned tolerance to analgesia.