Migraine is a common disorder that affects more than a billion of people worldwide, with an incidence in women three times higher than in men. The medical need for new therapeutic treatments is only partially satisfied by innovative approaches, and a significant percentage of migraineurs are still not satisfied with their therapy. Several lines of evidence links migraine to the activation of the NLRP3-IL-1β pathway. The aim of this research was to test whether NLRP3 blockers may represent innovative therapeutics for migraine. A well-established murine migraine model triggered by nitroglycerine (GTN) was used, together with NLRP3 knockout (Nlrp3^(-/-)) mice and the NLRP3 inhibitor MCC950. Both genetic and pharmacological blockade of NLRP3 were effective in reducing and preventing the onset of the periorbital mechanical allodynia (PMA) evoked by GTN in female mice, but not in males. The chronic administration of MCC950 was sufficient to induce PMA on its on, suggesting that the chronic treatment with a NLRP3 blocker may induce medication overuse headache as a side effect. Western blot analysis showed the activation of the NLRP3 pathway in the hippocampus of female mice treated with GTN, but not in their trigeminal ganglion, trigeminal nucleus caudalis and cortex. No activation of the NLRP3 pathway was detected in male mice. Collectively, this study strengthens the view that NLRP3 inhibitors may represent innovative migraine treatments. However, at the same time, it underlines for the first time some limitations that may affect NLRP3 inhibitors, namely sexual dimorphism in drug responsiveness and issues related to their chronic use.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.