The reliability of two prospective cortical biomarkers for pain: EEG peak alpha frequency and TMS corticomotor excitability

Many pain biomarkers fail to move from discovery to clinical application, attributed to poor reliability and feasible classifications of at-risk individuals. Preliminary evidence has shown that higher pain sensitivity is associated with slow peak alpha frequency (PAF) and depression of corticomotor excitability (CME). The present study evaluated the reliability of these measures, specifically whether, over several days of pain, a) PAF remains stable and b) individuals show two stable and distinct CME responses: facilitation and depression. Seventy-five healthy participants were given an injection of nerve growth factor (NGF) into the right masseter muscle on Day 0 and Day 2, inducing sustained pain. Electroencephalography (EEG) to assess PAF and transcranial magnetic stimulation (TMS) to assess CME were recorded on Day 0, Day 2 and Day 5. PAF reliability was in the excellent range even without standard pre-processing and ~2 minutes recording length. Moreover, two distinct and stable CME responses were demonstrated: facilitation and depression. These findings support the notion that PAF is a stable trait characteristic, with reliability unaffected by pain, and excellent reliability achievable with minimal pre-processing and ~2 minutes recording, making it a readily translatable biomarker. Furthermore, the study showed novel evidence of two stable corticomotor adaptations to sustained pain. Overall, the study provides support for the reliability of PAF and CME as prospective cortical biomarkers