are the two modalities of nociception
. Many systemic
diseases are accompanied by persistent itch or recurrent itch attacks. In the mid-twentieth century it was shown that itch is fundamentally different from pain.
Itching is an exteroceptive sensation, and can be elicited only by stimulation of the skin or skin-to-mucosa transitional surfaces on the outside of the body. Itch is induced by a variety of stimuli, including mechanical, chemical, thermal, and electrical stimulation of the skin. Removal of the upper skin layers, which are innervated by peptidergic free nerve endings only completely removes the ability to perceive itch. Itch is never felt in muscle, joints, or inner organs, demonstrating the absence of an itch-signaling apparatus in deep tissue. The same substances that elicit itch upon intracutaneous injection elicit only pain when injected subcutaneously. Electrical field stimulation of the skin elicits itching, the magnitude of which depends on stimulus frequency up to 40 Hz but is diminished at higher frequencies. This notion is consistent with the operating range of nociceptors.
Itching is reliably induced by a variety of chemical stimuli, the prime example of which is histamine. Histamine can be exogenously applied by injection, or pricking, or endogenously released from mast cells by other substances. Other biogenic amines (e.g., serotonin), kinins, some neuropeptides (e.g., substance P, VIP), and enzymes (endopeptidases like trypsin and papain) also elicit itch. However, their effects appear largely mediated by histamine (and possibly other mediators) released from cutaneous mast cells. The magnitude of itch is significantly diminished by H1-receptor antagonists or, for histamine releasers, by prior depletion of mast cells.
Only a few substances are known to induce a state of enhanced itch sensitivity (hyperknesis). Notably, although peripherally applied opioids have analgesic action in peripheral tissue, they aggravate histamine itch, an effect that is independent of the mast cell–degranulating properties of opioids or prostaglandin formation and can not be reversed by naloxone.
Itch induces a scratch reflex directed to the appropriate skin site in many animals and humans. The scratch behavior is specific for itching and differentiates itch from pain, which will rather lead to withdrawal or guarding behavior. Attempts to scratch the stimulated area have been observed in completely spinalized animals. The scratch reflex may thus be present already at the spinal level. Itch is probably conducted in the same ascending spinal pathways as is pain. Cordotomy of the anterolateral tract blocks the perception of pain and itch.
Neuroscience, Sinaur Associates (QP355.2.N487 1997)