Disease mechanisms in neuropathic itch

Abstract

Itch, also known as pruritus, is an unpleasant cutaneous sensation that provokes the desire to scratch. Itch is a common symptom of inflammatory skin disorders, but it can also occur in neurological diseases associated with injury to nervous tissue, in the absence of any skin disease and without any notable physiological stimuli in the periphery. This 'neuropathic' type of itch occurs either in combination with neuropathic pain or independently and is thought to be underdiagnosed. In this Review, we describe the physiological characteristics of specific neuronal systems in the PNS and CNS that transmit and process pruriceptive information, and we consider pathological changes that occur in these systems after nerve lesions. We then introduce a classification system for itch and highlight the similarities and differences between neuropathic itch and neuropathic pain. A summary of neuropathic syndromes in the PNS and CNS that are associated with itch is presented. Finally, we propose appropriate treatment strategies for neuropathic itch, in view of the fact that this condition has different mechanisms of itch generation to other types of itch and consequently requires different therapies.

Pruritus Epidemiology and Quality of Life

“…In 1660, German physician Samuel Hafenreffer defined pruritus as "an unpleasant cutaneous sensation that provokes the desire to scratch" (Binder et al 2008). This description may seem rather imprecise, but the myriad of parameters characterizing pruritus (e.g., severity, location, frequency, duration) and the absence of any consistent physical signs make defining pruritus difficult.…”

The G Protein–Coupled Receptor–Transient Receptor Potential Channel Axis: Molecular Insights for Targeting Disorders of Sensation and Inflammation

“…However, chronic pruritus is insensitive to antihistamine treatment. Chronic itch is commonly associated with dermal diseases and metabolic disorders and can be classified according to the source or cause of the pruritic symptoms: dermal or peripheral itch (e.g., dermatitis, psoriasis), neurogenic itch (e.g., chronic renal failure, cholestatic liver disease), and neuropathic itch (e.g., multiple sclerosis, diabetes) (Binder et al, 2008).…”

“…However, dermal and metabolic diseases can lead to chronic pruritus that is resistant to antihistamine drugs and is poorly understood and difficult to treat. Neuropathic itch is caused by many neurologic disorders (Binder et al, 2008). For example, the pruritus of patients with cholestatic liver disease can be so profound and intractable that it is an indication for liver transplantation (European Association for the Study of Liver, 2009).…”

B-type (brain) natriuretic peptide and pruritus in hemodialysis patients

“…29 Neuropathic pruritus is common in patients with diabetic peripheral neuropathy and arises from damage to unmyelinated C-fibers. 30 C-fibers have been divided into peptidergic and non-peptidergic subsets, mainly on the basis of neurochemical criteria. A large subset of peptidergic neurons expresses TRPV1, and TRPV1 knockout mice show deficits in histamine-evoked scratch response.…”