Chronic Itch: Gastrointestinal Peptides as Possible Contributors

Chronic itch (itch last 6 weeks or longer) is a clinical challenge, and is associated with a number of dermatologic, systemic, neuropathic, and psychogenic causes. Transmission of the itch sensation is similar to that of pain, but distinct in several ways. Scientists have found itch-specific neuronal pathways that when activated, cause considerable discomfort for patients. Current available treatments, however, are still more trial-and-error than evidence-based.

The February 2015 issue of Current Opinion in Endocrinology, Diabetes and Obesity discusses recent advances in chronic itch, narrowing the discussion to gastrointestinal (GI) peptides, specifically gastrin-releasing peptide (GRP), substance P, and their respective receptors. These peptides have traditionally been considered GI peptides. They are present in many different tissues, however, and seem to have a unique role in itching. They also may be the path to better, more targeted treatments for itching.

Scientists have been able to identify several itch-producing substances (pruritogens) and neurotransmitters that signal neuronal transmission of the unpleasant itch sensation. GRP and its high-affinity GRP receptor (GRPR) appear to the major regulators in the spinal cord itch pathway, and scientists suspect they may have a role in perpetuating itch from an acute sensation to a chronic problem. Some small studies have found that inhibiting GRP can lessen itch.

In the spine, several neuropeptides (eg, GRP, neuromedin B, and substance P) work together to promote or depress itch signals. These neuropeptides also contribute to acute and chronic inflammation and pain, fibrosis, functional disorders of the intestine and urinary bladder, infection, and cancer.

The most clinically promising work includes studies demonstrating that neurokinin 1 receptor antagonists might provide relief from chronic itch. Mouse and human studies have shown that intractable chronic pruritus sometimes responds to neurokinin 1 receptor antagonists (ie, aprepitant), decreasing itch intensity and the urge to scratch. Studies are underway to determine if oral and topical dosage forms may be helpful for patients plagued with itch.