Aims: To compare the modulatory effects of tonic mechanical or thermal craniofacial painful conditioning stimuli on pain sensitivity in craniofacial and spinal test sites in healthy men and women. Methods: Mechanical and cold headbands were developed and tested on 12 healthy men and 12 age-matched women (mean ± SEM: 27 ± 1.5 years). The pressure applied by the mechanical headband around the skull above the eyebrows could be adjusted over time via feedback from a 0 to 10 electronic visual analog scale (VAS) to maintain the pain intensity at a given level for 10 minutes (3 to 7 on VAS). The cold headband consisted of a series of plastic bags filled with antifreeze water having a temperature of approx 3°C. During the 10 minutes of application, the subjects were asked to rate the pain intensity on a 10-cm VAS. Pressure pain thresholds (PPT) were recorded over the right and left masseter muscles (MAR, MAL), right splenius muscle (neck), right elbow (elbow), and right middle finger (finger) by a pressure algometer (1-cm2 area probe). The PPTs at each of the five sites were determined at baseline and during the mechanical or cold-induced pain. The two sessions with mechanical or cold headbands were performed at an interval of 30 minutes. Results: Women had significantly lower absolute PPT values than men at most test sites (Unpaired t-test: P .027). The mechanical headband caused pain in both men (peak pain mean ± SEM: 4.7 ± 0.4 cm) and women (4.9 ± 0.4 cm) (P = .455). A significant PPT elevation was found at MAR, MAL, neck, and finger in men (11% to 17%; P .031) and at MAR, MAL, and neck in women (15% to 22%; P .020) during the mechanical-induced pain. The cold headband caused pain in both men (4.0 ± 0.4 cm) and women (4.5 ± 0.4 cm) (P = .285). During the cold-induced pain, a significant PPT elevation was found at all test sites in men (P .023) and at all sites (P .021) except for the finger in women. The relative changes in PPT values were not significantly different between men and women at any test site (unpaired t-test: P > .446). Conclusion: This study has documented that mechanical and thermal painful tonic stimuli applied to the craniofacial region can evoke diffuse noxious inhibitory control (DNIC)-like effects in the craniofacial region as well as spinally innervated areas, but without sex differences. Keywords: DNIC, human experimental pain models, sensory physiology, trigeminal pain