Dim Light at Night Exposure Induces Cold Hyperalgesia and Mechanical Allodynia in Male Mice

Abstract

The growing presence of artificial lighting across the globe presents a number of challenges to human and ecological health despite its societal benefits. Exposure to artificial light at night, a seemingly innocuous aspect of modern life, disrupts behavior and physiological functions. Specifically, light at night induces neuroinflammation, which is implicated in neuropathic and nociceptive pain states, including hyperalgesia and allodynia. Because of its influence on neuroinflammation, we investigated the effects of dim light at night exposure on pain responsiveness in male mice. In this study, mice exposed to four days of dim (5 lux) light at night exhibited cold hyperalgesia. Further, after 28 days of exposure, mice exhibited both cold hyperalgesia and mechanical allodynia. No heat/hot hyperalgesia was observed in this experiment. Altered nociception in mice exposed to dim light at night was concurrent with upregulated interleukin-6 and nerve growth factor mRNA expression in the medulla and elevated μ-opioid receptor mRNA expression in the periaqueductal gray region of the brain. The current results support the relationship between disrupted circadian rhythms and altered pain sensitivity. In summary, we observed that dim light at night induces cold hyperalgesia and mechanical allodynia, potentially through elevated neuroinflammation and dysregulation of the endogenous opioid system.

Keywords: allodynia; hyperalgesia; light at night; neuroinflammation; opioid; pain.

Figure 1.

dLAN increases body mass and disrupts timing of food consumption in male mice. Mice housed in dLAN for four weeks had a greater percentage increase in body mass compared to baseline measurements (A). dLAN altered food consumption, resulting in decreased active phase food consumption (B) and increased inactive phase food consumption (C). Error bars represent ± 1 SEM; *p < 0.05; ^#p < 0.05, Main effect of lighting condition, LMM.

Figure 2.

dLAN exposure induces cold hyperalgesia and mechanical allodynia. Mice exposed to dLAN displayed reduced cold plate withdrawal latencies after 3–4 nights (acute) and after 27–28 nights (chronic) of dLAN exposure (A). dLAN housing did not alter hot plate withdrawal latencies (B). At the chronic time point, dLAN mice displayed reduced mechanical withdrawal thresholds in the electric von Frey test (C). Error bars represent ± 1 SEM; *p < 0.05; ^#p < 0.05, Main effect of lighting condition, LMM.

Figure 3.

dLAN upregulates Il-6 and Ngf relative expression in the medulla. Mice housed in dLAN for four weeks had upregulated levels of Il-6 (A) and Ngf (D) within the medulla. dLAN housing did not alter Tnf-α, Il-1β, Bdnf, or Tac1 relative expression (B, C, E, F). Error bars represent ± 1 SEM; *p < 0.05.

Figure 4.

Cytokine, neurotrophin, and peptide transcripts examined in the L3–5 DRG were not affected by dLAN. Il-6, Il-1β, Tnf-α, Tac1, Ngf, and Bdnf relative expression levels were unaffected (D-F). Gene expression of the ion channel receptors Trpa1 and Trpm8 was unaltered at the time of tissue collection (G, H). Error bars represent ± 1 SEM; *p < 0.05.

Figure 5.

Cytokine, neurotrophin, and peptide transcripts in the lumbar region of the spinal cord were not affected by dLAN. Il-6, Il-1β, Tnf-α, Ngf, and Bdnf levels were not different between groups at the time of tissue collection (A-E). Error bars represent ± 1 SEM; *p < 0.05.

Figure 6.

dLAN increases Mor relative expression in the PAG. Il-6, Il-1β, and Tnf-α levels were not different in the PAG of dLAN mice (A-C). Expression of Ngf and Bdnf was unaffected in the PAG (D, E). Mor expression was upregulated in dLAN mice (F). Error bars represent ± 1 SEM; *p < 0.05.