Objectives The main aim was to determine the effects of percutaneous (PENS) and transcutaneous (TENS) electrical nerve stimulation on endogenous pain mechanisms in patients with musculoskeletal pain. Design A systematic review and meta-analysis. Methods The search was conducted on March 1, 2022, in EMBASE, CINAHL, PubMed, PEDro, Cochrane Library, Web of Science, Medline and SCOPUS databases. Randomized controlled trials (RCTs) comparing the use of transcutaneous or percutaneous electrostimulation with a placebo, control group or standard treatment in patients with musculoskeletal pain were included. Outcome measurements were QST somatosensory variables like pain threshold at pressure (PPT), conditioned pain modulation (CPM) and temporal summation of pain (TSP). The pooled data were evaluated with Review Manager 5.4. Results Twenty-four RCTs (N = 24) were included in the qualitative analysis and 23 in the meta-analysis. The immediate effects of PENS and TENS on local PPTs were significant with a moderate effect size (SMD 0.53, 95% CI: 0.34 to 0.72, p < 0.00001). When only studies with a lower risk of bias were analyzed, the heterogeneity from I2=58% (P < 0.00001) to I2=15% (P = 0.01) and a decrease in the overall effect was observed (SMD 0.33, 95% CI: 0.7 to 0.58). The short-term effects on local PPTs were not significant when compared to the control group (P = 0.13). The mid-term effects on local PPTs were significant showing a large effect size (SMD 0.55, 95% CI: 0.9 to 1.00, p = 0.02). The immediate effects on CPM were significant with a large effect size (SMD 0.94, 95% CI: 0.48 to 1.41, p < 0.0001). Conclusion PENS and TENS have a mild-moderate immediate effect on local mechanical hyperalgesia in patients with musculoskeletal pain. It appears that these effects are not sustained over time. Analyses suggest an effect on central pain mechanisms producing a moderate increase in remote PPT and in the case of PENS on CPM, but further studies are needed to draw clearer conclusions.