A possible neural mechanism for photosensitivity in chronic pain

Abstract

Patients with functional pain disorders often complain of generalized sensory hypersensitivity, finding sounds, smells, or even everyday light aversive. The neural basis for this aversion is unknown, but cannot be attributed to a general increase in cortical sensory processing. Here we quantified the threshold for aversion to light in patients with fibromyalgia, a pain disorder thought to reflect dysregulation of brain pain-modulating systems. These individuals expressed discomfort at light levels substantially lower than healthy controls. Complementary studies in lightly anesthetized rat demonstrated that a subset of identified pain-modulating neurons in the rostral ventromedial medulla unexpectedly responds to light. Approximately half of the pain-facilitating “ON-cells” and pain-inhibiting “OFF-cells” sampled exhibited a change in firing with light exposure, shifting the system to a pro-nociceptive state with activation of ON-cells and suppression of OFF-cell firing. The change in neuronal firing did not require a trigeminal or posterior thalamic relay, but was blocked by inactivation of the olivary pretectal nucleus. Light exposure also resulted in a measurable but modest decrease in the threshold for heat-evoked paw withdrawal, as would be expected with engagement of this pain-modulating circuitry. These data demonstrate integration of information about light intensity with somatic input at the level of single pain-modulating neurons in the brainstem of the rat under basal conditions. Taken together, our findings in rodents and humans provide a novel mechanism for abnormal photosensitivity, and suggest that light has the potential to engage pain-modulating systems such that normally innocuous inputs are perceived as aversive or even painful.

Long-lasting antinociceptive effects of green light in acute and chronic pain in rats

“…Finally, a retrograde labeling of the PAG demonstrated glutamate-like immunoreactivity in several regions of the brain including the occipital cortices [4], further supporting a link between the visual system and pain response. Martenson and colleagues [51] have recently identified a possible circuitry for photic stimulation that included pain modulating “ON-cells” and “OFF-cells” in the RVM which project to the dorsal horn of the spinal cord where they are postulated to modulate somatosensory processing. An imbalance of these may lead to enhanced or diminished pain with ON-cells facilitating nociception and OFF-cells inhibiting nociception.…”

Neuropathic pain-induced enhancement of spontaneous and pain-evoked neuronal activity in the periaqueductal gray that is attenuated by gabapentin

“…It has been previously reported that off-cells in the RVM that are associated with descending inhibitory analgesic pathways receive inputs from glutamatergic vlPAG projection neurons [33; 42; 59]. Numerous studies show a shift in homeostatic balance from descending inhibitory drive to descending facilitatory drive in the RVM that may contribute importantly to chronic pain states [9; 12; 25; 35; 40; 41; 55; 64; 68]. It is unclear whether this shift to descending facilitatory drive also occurs in the PAG, or involves upstream projections from the RVM.…”

Parabrachial complex links pain transmission to descending pain modulation

“…A number of cell parameters, defined as previously described, 1,11,50 were used to characterize reflex-related changes in RVM cell activity. In experiments testing heat-evoked withdrawals, we analyzed the number of spikes per ON-cell burst, the latency from burst onset to hindpaw withdrawal, and the peak firing rate during the burst.…”