Itch (pruritus) has many causes. Allergies and inflammatory skin disease all produce itch as a symptom. Pathophysiologically, the sensation of the itch is poorly understood. Nevertheless, there are many known inducers of itch. Histamine is wildly known as an inducer of the itch sensation. Other substances known to induce itch are substance P, cytokines, and proteases. Temperature also has an effect. It is conventional opinion that applied cold temperature inhibits itch by inhibiting C-fiber activity. However, studies have also described paradoxical phenomena associated with temperature and itch, where applied short-term moderate cold temperature stimulus enhanced the itch. Such a phenomenon might be explained by "paradoxical heat", which is when one has the perception of heat when, in fact, the skin is innocuously cooled. Thus, the exact effect of temperature on itch remains unclear, with different levels of heat and cold proven to both enhance and inhibit itch. Alcohol is known to have close interactions with histamine release. Alcohol both stimulates the release of histamine from mast cells and inhibits its degradations by inhibiting diamine oxidase. Though histamine is used by the body to mediate alcohol-induced gastric and intestinal damage as well as alcohol flushing, it is possible that elevated levels of histamine might have a correlation with referred itch (or even itch in general). An itch, also known as pruritus, is classified as a sensory stimulation to scratch a certain area of the skin. An itch can be a fleeting sensation, as with a random tickle or prick, or persistent, as with a rash such as eczema or other skin irritant such as an allergen. Itch has been demonstrated to be closely related to pain and to share many of its physiological mechanisms. The relationship between pain and itch is evident in the fact that itch sensations occur along a similar neurological and sensory pathway as sensations of pain, and the fact that individuals who are insensitive to pain are also insensitive to itch. Itch is induced by mechanical, chemical, thermal, or electrical stimuli of sensory receptors in the peripheral nervous system, or by psychological prompts. The receptors that are responsible for the sensation of itch caused by environmental stimuli are found within the upper layers of the skin. Once stimulated, usually by histamine within the body, a signal is sent through the peripheral nervous system to the brain (thalamus), where the information is processed and the command for the bodily response is issued. Itch can also originate as a result of damage to the nervous system (central or peripheral) or in response to the presence of excess opioids.