Electroacupuncture Modulates Programmed Cell Death 1 Ligand 1 on Peripheral and Central Nervous Systems in a Mouse Fibromyalgia Pain Model

<b>Background:</b> Fibromyalgia, a chronic condition that causes long-lasting pain over several months, is a global medical issue with both personal and societal implications. It is one of the hardest types of pain to heal, given the lack of objective parameters for diagnosis and progression evaluation. The main symptoms of fibromyalgia are long-lasting widespread pain alongside with anxiety, fatigue, sleep disorders, cognitive dysfunction, and obesity. Programmed cell death 1 ligand 1 (PD-L1) has been used as a target in cancer immunotherapy. It can inhibit acute and chronic pain by suppressing nociceptive neuron activity via PD-1 receptors. <b>Methods</b>: The current study aimed to investigate the role of PD-L1/PD1 in a mouse fibromyalgia pain model. Mice were exposed to intermittent cold stress (ICS) to produce a murine fibromyalgia model characterized using von Frey and Hargreaves tests. <b>Results</b>: The ICS-induced mice fibromyalgia pain model showed mechanical (2.26 ± 0.18 g) and thermal (4.36 ± 0.31 s) hyperalgesia. Nociceptive responses could be relieved with electroacupuncture, intracerebral PD-L1 injection, or <i>Trpv1</i> deletion. We also identified a lower PD-1 level in the dorsal root ganglion, spinal cord, thalamus, and somatosensory cortex. In contrast, levels of pain-related kinases increased after fibromyalgia induction, an effect which could be reversed by EA, PD-L1, or <i>Trpv1</i> deletion. <b>Conclusions</b>: Our findings shed light on the contribution of PD-L1/PD1 to EA and fibromyalgia pain, indicating its potential as a treatment target for fibromyalgia.