Exposure to Green Light-emitting Diodes Alleviates Endometriosis-associated Pain in Mice with Induced Deep Endometriosis.

Extensive preclinical and clinical studies have shown that exposure to green light-emitting diodes (gLED) exerts analgesic effect. We hypothesized that exposure to gLED alleviates endometriosis-associated pain. To test this, we induced deep endometriosis in 16 Balb/C female mice. Four weeks post-induction, the mice were randomized into gLED and white LED (wLED) groups (n = 8 each), exposed daily to gLED (520–525 nm in wavelength) and wLED (500–700 nm), respectively, for 8 h over 2 weeks, and were then sacrificed. Endometriotic lesions were weighed and analyzed via immunohistochemistry for E-cadherin, α-Sma, phosphorylated Creb (p-Creb), adrenergic receptor β2 (Adrb2), α7 nicotinic acetylcholine receptor (α7nAChR), κ- and µ-opioid receptors (Kor and Mor), and cannabinoid receptor 1 and 2 (Cb1 and Cb2), alongside Masson trichrome staining. Pain and depression-like behavior was assessed via hotplate tests, tail suspension tests and sucrose preference tests, and serum noradrenaline levels were quantified. Exposed to gLED significantly reduced lesion weight, shortened tail suspension immobility time and increased hotplate latency compared to wLED. Lesions from gLED mice exhibited significantly reduced α-Sma staining, marginally reduced fibrosis, and elevated systemic noradrenaline. IHC analysis revealed significantly lower staining of p-Creb, Adrb2, Cb1 and Cb2 but increased α7nAChR and Mor staining in gLED lesions. These results demonstrate that exposure to gLED significantly alleviates endometriosis-induced pain while decelerates lesional progression in mice with induced deep endometriosis, possibly through the suppression of the Creb-Adrb2-Cb2 signaling pathway as well as increased systemic noradrenaline levels. This raises the possibility of using gLED as a stand-alone or an adjuvant non-pharmacological therapy to alleviate endometriosis-associated pain.