Aβ Low Threshold Mechanoreceptors Contribute to Sensory Disturbances in Fibromyalgia

Overview

This study identifies a novel role for Aβ low threshold mechanoreceptors (Aβ-LTMRs) in the sensory abnormalities experienced by fibromyalgia (FM) patients. Circulating IgG from FM patients sensitizes these large diameter sensory fibers to mechanical and cold stimuli, correlating with symptoms such as tingling and cold-evoked pain.

Background

Fibromyalgia syndrome is a chronic pain disorder characterized by widespread pain, fatigue, and sensory disturbances including tactile allodynia, paraesthesia, and dysaesthesia. Previous research has focused on small fiber neuropathy and nociceptor hyperexcitability, but sensory abnormalities suggest involvement of large diameter sensory fibers as well. Passive transfer of IgG from FM patients to mice induces mechanical and cold hypersensitivity, implicating immune-mediated mechanisms in FM pathophysiology.

Data Highlights

In mice treated with FM IgG, there was increased sensitivity to innocuous mechanical stimuli and cold, accompanied by sensitization of Aβ-LTMR afferents. Microneurography in FM patients showed a higher proportion of Aβ-LTMRs responding to cold stimulation, though these fibers exhibited reduced mechanical responses compared to controls. Clinical questionnaires correlated sensory symptoms such as tingling with disease impact.

Key Findings

• FM IgG sensitizes large diameter Aβ-LTMRs to mechanical and cold stimuli in mice both ex vivo and in vivo.
• Aβ-LTMRs from FM patients show increased cold sensitivity but decreased mechanical responsiveness compared to healthy controls.
• Sensory symptoms like tingling and cold-evoked pain in FM correlate with IgG-mediated alterations in Aβ-LTMR function.
• FM is associated with both functional and structural abnormalities in peripheral sensory neurons, including large myelinated fibers.
• Passive transfer of FM IgG causes behavioral hyperresponsiveness to light touch and cold in mice, implicating autoreactive antibodies in sensory disturbances.

Clinical Implications

These findings suggest that sensory abnormalities in FM extend beyond small fiber neuropathy to include large diameter mechanoreceptors, mediated by autoreactive IgG. Clinicians should consider the role of immune mechanisms affecting Aβ-LTMRs when evaluating sensory symptoms such as tactile allodynia and cold-evoked pain in FM patients. Targeting IgG-mediated sensitization may offer new therapeutic avenues.

Conclusion

The study expands the understanding of fibromyalgia pathophysiology by demonstrating that autoreactive IgG sensitizes Aβ low threshold mechanoreceptors, contributing to sensory disturbances. This insight informs future research and potential treatments targeting immune-mediated sensory dysfunction in FM.

References

1. Themistocleous et al. 2022 -- Scientific Commentary on Aβ Low Threshold Mechanoreceptors in Fibromyalgia