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

Background: Fibromyalgia (FM), 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 lacking objective parameters for diagnosis and progression evaluation. The main symptoms of FM are long-lasting widespread pain together with anxiety, fatigue, sleep disorder, cognitive dysfunction, and obesity. Programmed cell death 1 ligand 1 (PD-L1) has been used as target in cancer immunotherapy. PD-L1 can inhibit acute and chronic pain by suppressing nociceptive neuron activity via PD-1 receptors. Methods: The current study aimed to investigate the role of PD-L1/PD1 in a mouse FM pain model. Mice were exposed to intermittent cold stress (ICS) to produce a murine FM model characterized through von Frey and Hargraves’ tests. Results: The ICS-induced mice FM pain model showed mechanical (2.26 0.18 g) and thermal (4.36 0.31 s) hyperalgesia. Nociceptive responses could be relieved by electroacupuncture (EA), intracerebral PD-L1 injection, or Trpv1 deletion. We also identified a lower PD1 level in dorsal root ganglion, spinal cord, thalamus, and somatosensory cortex. In contrast, levels of pain-related kinases increased after FM induction. Effects which could be reversed by EA, PD-L1, or Trpv1 deletion. Conclusions: Our findings shed light on the contribution of PD-L1/PD1 to EA and FM pain, indicating its potential as a treatment target for fibromyalgia.