# Reduced Descending Itch Inhibition in Peripheral Neuropathy Patients With Chronic Pruritus

## TL;DR

This study finds that patients with peripheral neuropathy and chronic itching have reduced natural itch inhibition, which may explain why they experience long-lasting itch.

## Contribution

The study introduces a novel CIM protocol and identifies reduced descending itch inhibition as a potential mechanism for chronic pruritus in peripheral neuropathy.

## Key findings

- Chronic pruritus in peripheral neuropathy is associated with reduced endogenous itch inhibition.
- Painful cold stimuli similarly reduce itch across all groups, but PNPPRU patients show shorter itch inhibition.
- CIM effects are significantly shorter in PNPPRU patients compared to controls and PNPNO-PRU patients.

## Abstract

Peripheral neuropathies (PNP) cause a wide range of symptoms of which pruritus and pain are a major burden to patients. Clarifying their mechanisms will facilitate the adequate symptom management. In contrast to neuropathic pain, neuropathic pruritus has long been understudied. We investigate inhibitory pruritus mechanisms in patients with PNP.

A total of 39 participants (median age: 57 years [27–81], 25♀/14♂), including 16 patients with PNP and pruritus (PNPPRU) and 8 with PNP but without pruritus (PNPNO‐PRU), and 15 controls, were enrolled and phenotyped using dynamic and static quantitative sensory testing, determination of intradermal nerve fibre density, and conditioned pain (CPM) and itch (CIM) modulation. For CIM, an electrically induced itch test stimulus (TS) was applied with an individual itch intensity of > 30 NRS (0–100). A cold‐water bath (contralateral side) served as the conditioning stimulus (CS). Itch, pain intensity and the desire to scratch upon TS were rated before, during and after the CS was applied.

Using our novel CIM protocol, well‐controlled and stable itch was electrically induced in controls and in both PNP groups, regardless of whether or not pruritus was a symptom. Concomitant painful cold stimuli reduced electrically induced itch in all three groups to a similar degree. However, PNPPRU patients had significantly shorter itch inhibition (CIM effects) compared to controls and PNPNO‐PRU, whereas CPM effects were not different between groups.

The results show reduced endogenous itch inhibition in patients with chronic itch, which represents a possible mechanism of chronic pruritus in PNP.

Reduced itch inhibition is associated with the symptom of chronic pruritus in PNP patients, suggesting that reduced descending itch inhibition may facilitate chronic itch in peripheral neuropathy.