PD-L1 and PD-1 expressed in trigeminal ganglia may inhibit pain in an acute migraine model

Background Neurogenic inflammation, mediated by the activation of primary neurons, is thought to be an important factor in migraine pathophysiology. Programmed cell death ligand-1 (PD-L1) can suppress the immune response through the Programmed cell death-1 receptor. However, the role of PD-L1/PD-1 in migraine remains unclear. In this study we evaluated the expression and role of PD-L1/PD-1 in the trigeminal ganglia in an animal model of acute migraine. Methods Acute nitroglycerin induces acute mechanical hyperalgesia that can be used as a readout of migraine-like pain. We investigated the expression of PD-L1 and PD-1 in the trigeminal ganglia in a mouse model by means of immunofluorescence labeling, quantitative reverse transcription-polymerase chain reaction and western blotting. We explored the effects of PD-1 in a migraine model by the von Frey test and by analyzing the expression of calcitonin gene-related peptide, interleukin-1β (IL-1β), interleukin-18 (IL-18), Tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and transient receptor potential vanilloid (TRPV4) after the intravenous injection of a PD-1 inhibitor. Results PD-L1 and PD-1 immunoreactivity were present in healthy trigeminal ganglia neurons. The mRNA levels of PD-L1 and PD-1 were significantly elevated 2 h, 4 h and 6 h after acute nitroglycerin treatment ( p < 0.05). The protein levels of PD-L1 were significantly increased 2 h, 4 h and 6 h after treatment, and PD-1 was significantly increased at 2 h and 6 h. The blockade of PD-1 increased acute nitroglycerin-induced hyperalgesia, and this effect was accompanied by a more significant increase in calcitonin gene-related peptide, IL-1β, TNF-α, IL-6 and IL-18 in the trigeminal ganglia. Conclusion These findings suggest that PD-L1 and PD-1 might inhibit migraine-like pain by downregulating CGRP and inflammatory factors in the trigeminal ganglia. The use of PD-L1 and PD-1 as analgesics should be further studied.