Neuropathic Itch

Abstract

Chronic itch can be caused by dysfunctions of itch-sensing neurons that produce sensory hallucinations of pruritogenic stimuli. The cellular and molecular mechanisms are still unknown. All neurological disease categories have been implicated and neurological causes should be considered for patients with otherwise-unexplained itch. The same neurological illnesses that cause neuropathic pain can also or instead cause itch. These include shingles (particularly of the head or neck), small-fiber polyneuropathies, radiculopathies (e.g., notalgia paresthetica and brachioradial pruritis) and diverse lesions of the trigeminal nerve, root, and central tracts. Central nervous system lesions affecting sensory pathways, including strokes, multiple sclerosis, and cavernous hemangiomas can cause central itch. Neuropathic itch is a potent trigger of reflex and volitional scratching although this provides only fleeting relief. Rare patients whose lesion causes sensory loss as well as neuropathic itch can scratch deeply enough to cause painless self-injury. The most common location is on the face (trigeminal trophic syndrome). Treating neuropathic itch is difficult; antihistamines, corticosteroids, and most pain medications are largely ineffective. Current treatment recommendations include local or systemic administration of inhibitors of neuronal excitability (especially local anesthetics) and barriers to reduce scratching.

Itch Mechanisms and Circuits

“…Neuropathic itch arises from nerve damage at any point along the neural pathway (98). Despite fundamental advances in understanding the mechanisms of itch in the normal nervous system, virtually nothing is known about the cellular and molecular mechanisms of neuropathic itch.…”

Critical care and survival of fragile animals: The case of Prrxl1 knockout mice

“…Moreover, Prrxl1 −/− animals raised in more enriched cages also present alopecia although it does not progress to skin wounds. The abolishment/reduction of peripheral thin fibres, as seen in these animals is known to induce an abnormal itch sensation commonly called neuropathic itch (Bernhard, 2005;Oaklander, 2011), and this may be the cause for excessive grooming observed in some knockouts. On the other hand, the increased number of mast cells that we observed in the skin samples of knockout animals suggests an immune basis for the alopecia.…”

Microglia are Involved in Pruritus Induced by DNFB via the CX3CR1/p38 MAPK Pathway

“…Chronic itch, persisting for more than six weeks, may be a symptom of more serious dermatological or systemic diseases and can have a detrimental effect on an individual's quality of life. Neuropathic itch syndromes, in which the itch sensation appears out of proportion or independent of pruritogenic stimuli [4], are chronic conditions that result from peripheral or central nervous system dysfunction [5]and may potentially involve neuronal or glial damage [6,7]. Acute pruritus is mediated primarily by histamine-sensitive neurons in the skin [8] and may be partially alleviated by antihistamines or topical steroids [4].…”

“…Neuropathic itch syndromes, in which the itch sensation appears out of proportion or independent of pruritogenic stimuli [4], are chronic conditions that result from peripheral or central nervous system dysfunction [5]and may potentially involve neuronal or glial damage [6,7]. Acute pruritus is mediated primarily by histamine-sensitive neurons in the skin [8] and may be partially alleviated by antihistamines or topical steroids [4]. The mechanisms underlying neuropathic pruritus, in contrast, have not been characterized and there are no effective treatments for this condition short of behavioral interventions and localized anesthetics to reduce the scratch reflex [5].…”