**Background:** Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain, fatigue, sleep disturbances, and emotional distress. Pain in FM is classified as nociplastic, arising from altered nociception without clear tissue damage or somatosensory system lesion. However, patients may experience overlap with nociceptive and neuropathic pain. Impaired pain processing, including central amplification and decreased descending modulation, is central, but peripheral small-fiber pathology is also frequently observed. FM is often underdiagnosed due to reliance on subjective symptoms and lack of biomarkers. This position statement from the Neuropathic Pain Study Group of the Italian Society of Neurology aims to provide practical guidelines for clinical and instrumental assessment of FM in neurological practice.
**Methods:** This is a position statement based on a non-systematic review. For clinical criteria, the American College of Rheumatology (ACR) criteria for adult and childhood FM were considered. For instrumental assessment, PubMed was searched for studies on neurophysiological, psychophysical, autonomic, and other techniques applied to FM, with special focus on sensory and autonomic neuropathy. Search strings are detailed in Table 1. Inclusion criteria were original studies, case-control design, use of standardized methodologies, and FM diagnosis per ACR criteria (2010, 2011, 2016). Reviews and case reports were excluded. A total of 47 studies were considered for small-fiber pathology assessment. Studies from the last 10 years were considered, with publications within 5 years (2018–2022) summarized in tables.
**Key Results:** The ACR diagnostic criteria have evolved: 1990 criteria emphasized tender points (≥11 of 18 sites) and diffuse pain for ≥3 months. The 2010 revision replaced tender points with subjective symptom scores. The 2011 version introduced the Fibromyalgia Severity Scale (FS score, 0–31) from the Widespread Pain Index (WPI) and Symptom Severity Score (SSS). The 2016 revision defines widespread pain as present in at least 4 of 5 regions (excluding jaw, chest, abdomen), specifies somatic symptoms, and states that FM diagnosis should be made regardless of other diagnoses. For juvenile FM (JFM), prevalence is 7–15% of pediatric rheumatology visits, with a 4:1 female-to-male ratio and diagnosis typically at 13–15 years. Diagnostic criteria for JFM were first described in 1985 and revised in 2010.
REGARDING INSTRUMENTAL ASSESSMENT
- Nerve conduction studies (NCS) and electromyography (EMG) are generally normal in FM, except for occasional mild sensory amplitude reductions (e.g., sural and medial plantar responses) in patients with neuropathic pain or metabolic syndrome.
- Laser-evoked potentials (LEPs) show increased amplitude and reduced habituation in some studies, supporting central pain hyperexcitability. However, other studies report normal LEP parameters, suggesting small-fiber pathology has negligible impact on somatosensory function. In 57 FM patients, Fasolino et al. found normal LEP parameters regardless of skin biopsy results. In 92 patients, Van Assche et al. found no signs of Aδ fiber loss. Recent studies (Vecchio et al., 2020, 2022) showed abnormal habituation index and reduced P2 amplitude, not coherent with denervation site.
- Autonomic assessment: Heart rate variability (HRV) studies consistently show altered sympatho-vagal balance with increased sympathetic and decreased parasympathetic activity. Sympathetic skin response (SSR) latency is significantly longer in FM, and response is absent in 15–18% of patients. Electrochemical skin conductance is impaired. Autonomic symptoms correlate with disease severity and pain intensity.
- Skin biopsy: Multiple studies show reduced intraepidermal nerve fiber density (IENFD) in a variable proportion of FM patients, often with a non-length-dependent pattern. In 155 FM patients, Lawson et al. found reduced IENFD at distal site in 28% and proximal site in 12%. Evdokimov et al. (2019) identified four subgroups: normal innervation (37%), distal reduction (17%), proximal reduction (31%), and both (15%). Higher pain intensity and anxiety were associated with generalized denervation. Morphological changes include reduced GAP43-positive regenerating fibers and increased peptidergic innervation of arteriole-venule shunts. Mitochondrial dysfunction and oxidative stress were also noted.
- Corneal confocal microscopy (CCM): Studies show reduced corneal nerve fiber density, length, and branching in FM, correlating with disease severity. Changes in Langerhans cells are also observed. CCM may predict therapeutic response to tapentadol.
- Microneurography: Limited studies show abnormal C-nociceptor firing, hyperexcitability, and increased mechanical sensitivity in FM, suggesting peripheral nociceptor dysfunction.
- Quantitative sensory testing (QST): Common findings include hypersensitivity to mechanical and thermal stimuli (e.g., increased mechanical pain sensitivity, reduced pressure pain thresholds, cold hyperalgesia). Dynamic allodynia and aftersensations are reported. Conditioned pain modulation (CPM) is less efficient, indicating altered endogenous pain mechanisms. Sensory phenotypes differ from small-fiber neuropathy.
**Clinical Implications:** The position statement recommends that neurologists apply the ACR 2016 criteria for FM diagnosis: WPI >7 and SSS >5, or WPI 4–6 and SSS >9. A careful neurological examination and rheumatologic consultation are advised. For small-fiber involvement, at least two of the following tests should be performed: HRV + SSR, laser-evoked responses, skin biopsy, or corneal confocal microscopy. Microneurography is rarely available. QST may be used but is subjective. If small-fiber impairment is confirmed, metabolic, immunological, and paraneoplastic causes should be investigated with blood tests, repeated at 1-year follow-up. This approach aims to exclude known causes of small-fiber neuropathy and identify genetic factors (e.g., voltage-gated ion channel abnormalities) to enable precision medicine. The document highlights the neurologist's role in diagnosing associated central and peripheral nervous system conditions and advancing research into FM pathophysiology.