Pain sensitivity is an adaptive process affected by expectation, mood, coping, operant conditioning, and the preconscious allocation of attention. Underlying mechanisms may include encoding of similar experiences (eg, depression, loss, pain-distress) in overlapping patterns of activation, failure of common regulatory mechanisms, direct top-down activation of the pain matrix, and changes in descending pain facilitatory and inhibitory tone. In theory, the combination of glial cell activation from psychological stress and neural firing from nociceptive input may be particularly likely to lead to pain sensitization and long-term structural changes in pain processing regions of the brain. In these ways, headaches in which chronicity, diffuseness, and distress seem better accounted for by psychological than by medical variables can be understood in neurobiological terms. This can allow psychological treatment of physical distress to be objective, nonthreatening, and relatively precise.