Sunburn Rapidly Reshuffles Pain-Signaling Neuropeptides in the Spinal Cord Within Hours

UVB irradiation of the rat heel rapidly altered neuropeptide levels in pain-processing areas. Galanin-positive neurons in the dorsal root ganglia (DRG) decreased significantly at most time points (2-96h), while galanin immunoreactivity increased in the spinal cord dorsal horn, central canal area, and lateral spinal nucleus from 12-96h. Substance P levels in DRG neurons remained unchanged, but substance P immunoreactivity increased in the dorsal spinal cord at 48h. The neuronal activation marker c-fos appeared in the dorsal horn and central canal area at 24-48h — the same timeframe when hyperalgesia peaks. Skin blood flow nearly doubled 24h after irradiation.

Rats received UVB irradiation to the heel area. At time points ranging from 2 to 96 hours post-exposure, dorsal root ganglia and spinal cord tissue at the L5 level were collected and analyzed by immunohistochemistry for galanin, substance P, and c-fos expression. Skin blood flow was measured using laser Doppler to confirm the inflammatory response.

Sunburn-induced pain (UVB hyperalgesia) is a well-established model for studying inflammatory pain that translates between rats and humans. This study shows that two neuropeptides — galanin and substance P — are rapidly redistributed in the pain-processing nervous system after UV exposure, peaking at the same time as heightened pain sensitivity. Understanding which neuropeptides drive sunburn pain could lead to better pain treatments and reveals fundamental mechanisms of how tissue inflammation is communicated to the spinal cord.

The UVB sunburn model is one of the most translatable pain models between rodents and humans — the pain timeline and characteristics are remarkably similar. This study maps how neuropeptides are redistributed during the development of inflammatory hyperalgesia, providing a molecular timeline that could help identify when interventions might be most effective. The finding that galanin moves from sensory neurons to the spinal cord is particularly interesting because galanin can either promote or inhibit pain depending on where it acts.

This is a rat study — the neuropeptide response timing and distribution may differ in humans. Only the L5 spinal level was analyzed, so changes at other spinal levels could have been missed. Immunohistochemistry shows protein distribution but doesn't distinguish between newly synthesized peptide and peptide that has been transported from elsewhere. The functional significance of the lateral spinal nucleus changes (an unusual finding) is unclear.