Temporal interaction information and laser evoked responses: preliminary results in fibromyalgia patients with small fibers pathology

Objectives: We propose a novel application of higher-order information-theoretic measures to assess the temporal interaction information (TII) between laser-evoked potentials (LEPs) and individual pain ratings in healthy subjects and patients with fibromyalgia (FM) affected by small fiber pathology. Methods: Seventy-nine FM patients, categorized into three groups based on skin biopsy findings (normal innervation n 19, proximal denervation n 53, and both proximal and distal denervation n 7), and 14 control subjects were studied. We used cluster-based permutation tests (p < 0.05) to identify significant clusters of TII between cortical components recorded using a 64-channel electroencephalography (EEG) system - with focus on the Cz electrode - and subjective pain ratings to quantify synergy or redundancy between the LEP signal time points and Visual Analog Scale (VAS). Results: Control subjects generally exhibited synergy clusters corresponding to N2 and P2 peaks, whereas patients with fibromyalgia (FM), particularly those with distal denervation, exhibited increased redundancy and decreased synergy. Conclusion: Patients with FM and small fiber pathology exhibited an alteration in higher-order integration mechanisms due to a complex interaction between cortical processing of pain and denervation of nociceptive fibers. Significance: These findings highlight the potential of TII in elucidating the complex interplay between peripheral nerve integrity and central sensitization in FM and other chronic pain disorders.