Brainstem pain-modulating neurons are sensitized to visual light in persistent inflammation

Many individuals with chronic pain report abnormal sensitivity to visual light, referred to as "photosensitivity" or "photophobia," yet how processing of light and nociceptive information come together remains a puzzle. Painmodulating neurons in the rostral ventromedial medulla (RVM) have been shown to respond to bright visual light in male rats: activity of pain-enhancing ON-cells is increased, while that of pain-inhibiting OFF-cells is decreased. Since the RVM is the output node of a well-known pain modulation pathway, light-related input to these neurons could contribute to photosensitivity. The purpose of the present study was to fully characterize RVM ON- and OFF-cell responses to visual light by defining stimulus-response curves in male and female rats across a range of intensities (30 to 16,000 lx). We also determined if light-evoked responses are altered in animals subjected to persistent inflammation. We found that ON- and OFF-cells responded to relatively dim light ( <1000 lx in na & iuml;ve animals), with no difference between the sexes in threshold for light-evoked changes in firing or the percentage of responsive cells. Second, light-evoked suppression of OFF-cell firing was enhanced in persistent inflammation, with no change in light-evoked activation of ON-cells. These data indicate that pain-modulating neurons can be engaged by dim light, even under normal conditions. Further, they suggest that decreased descending inhibition during light exposure could contribute to reduced nociceptive thresholds in chronic pain states, resulting in lightinduced somatic discomfort and aversion to light. Lastly, our findings argue for differences in how light and somatic stimuli engage RVM, and suggest that light-related input acts as a "top-down" regulatory input to RVM.