In general, the invention relates to the field of functional illnesses.
Many functional illnesses, e.g., pain and psychiatric disorders, may be correlated with central nervous system (CNS) activity. These illnesses are, however, typically assayed based on interviews or psychological tests. In addition, symptoms of a functional illness may be confused with an unrelated illness, or an unrelated illness may mask an underlying functional illness. Because of these limitations, functional illnesses are difficult to diagnose definitively, and the effectiveness of treatments may also be difficult to discern. This difficulty is exacerbated when a subject is unwilling or unable to articulate symptoms.
Pain is a complex response that has been functionally categorized into sensory, autonomic, motor, and affective components. The sensory aspect includes information about stimulus location and intensity while the adaptive component may be considered to be the activation of endogenous pain modulation and motor planning for escape responses. The affective component appears to include evaluation of pain unpleasantness and stimulus threat as well as negative emotions triggered by memory and context of the painful stimulus. Extensive electrophysiological research in animals has defined likely neuroanatomical substrates for some of the sensory attributes of pain, such as localization and intensity, and some of the adaptive responses, such as descending analgesia. Other regions activated by painful stimuli have also been identified which may be involved in the affective response; however, the neural substrates for the motivational and emotional response to pain remain a topic of debate.
In general, pain conditions can be divided into chronic and acute. Chronic pain includes neuropathic pain (e.g., post surgical and postherpetic neuralgia) and chronic inflammatory pain (e.g., arthritis), or pain of unknown origin (e.g. fibromyalgia) while acute pain usually follows non-neural tissue injury (e.g., tissue damage from surgery or inflammation, or migraine). Non-invasive techniques that measure neuronal activity in humans, including magnetoencephalography (MEG), single proton emission tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), are now being used to discern CNS pathways involved in pain.
Testing pharmacological agents in humans usually requires a number of steps including testing in healthy subjects and in patients with the disease, thus requiring the exposure of a large number of human subjects to a drug. In addition, quantitative data on drug screening in humans may also be difficult to obtain, especially for functional illnesses.