Tissue-specific peripheral sensory remodeling in chronic low back pain: established and emerging nociceptive niches
Front Mol Neurosci. 2026 Oct 5;19:1972635. doi: 10.3389/fnmol.2026.1972635. eCollection 2026.
ABSTRACT
Chronic low back pain arises from heterogeneous peripheral and central mechanisms, yet the sensory biology of individual lumbar tissues is rarely considered within a unified framework. This Mini Review compares peripheral sensory remodeling and sensitization across four candidate nociceptive niches: the intervertebral disc, vertebral endplate, thoracolumbar fascia, and paraspinal muscle. Disc pathology is characterized by nociceptive ingrowth, endplate pathology by osteochondral sensory remodeling and afferent sensitization, and thoracolumbar fascia by inflammation-associated remodeling of a pre-existing sensory network. Paraspinal muscle remains an emerging sensory-inflammatory niche in which muscle-spindle remodeling is distinct from unproven nociceptor remodeling. Across tissues, recurrent neurotrophic, inflammatory, neuropeptide, and mechanosensory mediators indicate molecular overlap but do not establish functional convergence within common sensory circuits. Dorsal root ganglia and the spinal dorsal horn are therefore considered candidate sites of downstream integration. We propose a dynamic multi-niche model with testable predictions for identifying active niches, tracking shifts in tissue contribution, and distinguishing causal nociceptive mechanisms from incidental degeneration. Future spatial, longitudinal, and epigenomic studies may enable molecular definition of active pain-generating states and mechanism-guided treatment.
PMID:42898630 | PMC:PMC13678379 | DOI:10.3389/fnmol.2026.1972635