Objective: The aim of this study is to assess whether pain-inducing manual pressure (PIMP) leads to effects on pressure pain threshold (PPT) mediated by conditioned pain modulation (CPM) and whether these effects are influenced by the intensity and repetition of the stimulus. Additionally, the influence of psychological factors and physical activity on the response to PIMP was explored. Methods: A total of 72 pain-free students were randomly assigned to three crossover trials. Trial 1 compared the effects of PIMP with the cold pressor task and pain-inducing electrostimulation. Trial 2 compared the effects of manual pressure that elicited moderate pain, mild pain, and no pain. Trial 3 compared a single PIMP stimulation with four stimuli applied at the same site or at different sites. Results: PIMP produced a lower increase in PPT than cold pressor task and no difference with electrostimulation. Manual pressure that caused moderate pain led to a greater increase in PPT compared to mild pain and pain-free application. Repetition of PIMP stimulus, whether at the same or different sites, did not significantly increase PPT compared to a single stimulation. No association with psychological factors or physical activity was found. Conclusions: PIMP produces an increase in PPT, suggesting the involvement of CPM-related mechanisms.