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Conditioned pain modulation (CPM) and temporal summation of pain (TSP) are 2 experimental paradigms capturing endogenous pain modulation, which have repeatedly demonstrated clinical relevance. Conditioned pain modulation describes the inhibition of the pain response to a test stimulus (Ts) when a second noxious stimulus, the conditioning stimulus (CS), is concurrently applied. Temporal summation of pain describes the enhanced pain response to a series of stimuli compared with single stimuli. Temporal summation of pain–limiting effects of CPM are likely but may depend on the stimulus modality of the Ts. This study aimed at investigating these differential effects of stimulus modality. Thirty-five healthy volunteers completed 2 experimental blocks (Ts modality: pressure vs heat) in balanced order. Both blocks consisted of 3 conditions: baseline (no CS), CPM1 (nonpainful CS: 42°C water bath), and CPM2 (painful CS: 46°C water bath). Single stimuli and series of stimuli were alternatingly applied to assess TSP by means of a Numerical Rating Scale. Both TSP and CPM were successfully induced with no difference between the 2 Ts modalities. We also detected a significant interaction between TSP and CPM, with higher pain reduction for a series of Ts compared with single Ts during the painful CS. Interestingly, this interaction was modality-dependent: TSP for heat Ts was completely abolished by CPM, whereas this was not the case for pressure Ts. Our findings suggest different forms of central sensitization induced by TSP using either heat or pressure stimuli, which differ in their susceptibility to CPM. Clinical implications and directions for future research are discussed.