Neuroimmune Phenotyping as the Next Frontier in Chronic Pain Medicine for Musculoskeletal Back Pain.

BACKGROUND

Chronic low back pain encompasses heterogeneous mechanical, neuropathic, nociplastic, and myofascial presentations that may reflect distinct neuroimmune mechanisms. We synthesized evidence linking these phenotypes to measurable biological features and clinically relevant treatment strategies.

METHODS

We conducted a structured literature search of MEDLINE, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials for studies published from January 2005 through January 2025. Systematic reviews, randomized controlled trials, and mechanistic studies addressing neuroinflammation, glial activation, central sensitization, biomarkers, or imaging were organized according to four clinically relevant pain phenotypes and translational readiness.

RESULTS

Neuroimmune findings differed across axial mechanical, radicular neuropathic, nociplastic, and myofascial pain. Imaging of the 18-kDa translocator protein demonstrated phenotype-associated neuroinflammatory patterns, whereas shear wave elastography provided an objective measure of myofascial trigger-point stiffness. Combining inflammatory biomarkers with psychosocial characteristics improved chronic pain prediction, with reported areas under the receiver operating characteristic curve ranging from 0.69 to 0.92. Evidence also supported phenotype-aligned approaches including targeted rehabilitation, ultrasound-guided dry needling, dorsal root ganglion stimulation, and spinal cord stimulation. However, biomarker validation, imaging standardization, and clinical availability varied substantially.

CONCLUSION

Neuroimmune phenotyping provides a framework for connecting pain mechanisms with diagnostic and therapeutic strategies in chronic low back pain. Shear wave elastography and selected inflammatory measures appear closest to clinical implementation, while advanced neuroimaging and multi-omic approaches remain investigational. Phenotype-enriched prospective trials are needed before routine precision-guided management can be established.