Aims: To use functional magnetic resonance imaging (fMRI) to determine whether orofacial cutaneous or muscle pain is associated with changes in primary motor cortex (M1) activity that outlast the duration of perceived pain, and whether these M1 changes are different during cutaneous pain compared with muscle pain. Methods: fMRI was used in healthy subjects experiencing orofacial muscle (n = 17) or cutaneous (n = 15) pain induced by bolus injections of hypertonic saline (4.5%) into the belly of the masseter muscle (0.5 ml) or subcutaneously (0.2 ml) into the overlying skin, respectively. To determine the effects of the injection volume, isotonic saline (n = 4) was injected into the masseter muscle. Results: Similar pain scores were observed following subcutaneous (mean [± SEM]; 4.73 ± 0.51) or intramuscular injections (4.35 ± 0.56). Orofacial muscle but not cutaneous pain was associated with a transient increase in signal intensity in the contralateral M1. Cutaneous and muscle orofacial pains were associated with similar signal intensity decreases within the contralateral M1 that continued to decrease for the entire scanning period. Isotonic saline did not evoke pain or changes in M1 signal intensity. Conclusion: The transient contralateral M1 signal intensity increase during orofacial muscle pain may underlie escape-like motor patterns. However, once the initial threat has subsided, longer-term reductions in M1 activity and/or excitability may occur to aid in minimizing movement of the affected part, an effect consistent with the general proposals of the Pain Adaptation Model. Keywords: face, jaw muscle, magnetic resonance imaging (MRI), pain, skin, trigeminal