Epidermal growth factor receptor-inhibition (EGFR-I) in the treatment of neuropathic pain.

ABSTRACT

BACKGROUND: Neurobiological work has demonstrated that expression of mitogen-activated protein kinases (MAPK) is upregulated on neurones and glial cells after nerve damage. Furthermore, the epidermal growth factor receptor (EGFR) has been identified as having a key role in this process and subsequent interruption of this using EGFR-Inhibitors (EGFR-I), may improve neuropathic pain. The aim of this report was to explore if EGFR-I attenuated neuropathic pain in humans. METHODS: A selection of patients with neuropathic pain were treated off-label with one of four EGFR-Is, approved for the treatment of cancer. All patients had chronic and severe neuropathic pain (as defined by diagnostic criteria). Pain intensity, interference with function, and adverse events were prospectively registered. RESULTS: Twenty patients were treated. Eighteen patients experienced clinically significant pain relief after treatment with EGFR-I. Median observed pain reduction for all patients was 8.5 (IQR=5-9.5) points on a 0-10 numeric rating scale. Neuropathic pain spike duration and frequency also improved. Pain relief was most often achieved within 24 h and was more rapid in cases of i.v. than oral administration. All four EGFR-I that were tested were of equal efficacy. The duration of pain relief was consistent with the individual drugs' half-lives. No cases of drug-tolerance were observed. Side-effects were predominantly skin reactions. One grade 3 adverse event was registered. Median follow-up for responders was 7 months (Range 1-37). CONCLUSIONS: EGFR-I improves neuropathic pain and this is in keeping with basic science work. Controlled clinical trials are now eagerly awaited to assess this further.