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. 2025 May 22:18:100186.
doi: 10.1016/j.ynpai.2025.100186. eCollection 2025 Jul-Dec.

Patient phenotyping for molecular profiling of neck and low back pain - Study protocol

Michele Curatolo  1   2 , Cathryn Payne  3 , Abby P Chiu  1 , Nguyen T Tran  3 , Natalie Yap  3 , Christoph P Hofstetter  3 , Joseph B Lesnak  4 , Asta Arendt-Tranholm  4 , Theodore J Price  4 , Jeffrey G Jarvik  5   2 , Judith A Turner  6
Affiliations

Patient phenotyping for molecular profiling of neck and low back pain - Study protocol

Michele Curatolo et al. Neurobiol Pain. .

Abstract

Background: Chronic neck and low back pain are highly prevalent, leading causes of disability, and associated with long-term opioid use. The development of effective therapeutics is hampered by the limited understanding of the molecular mechanisms underlying these conditions. The Human Nociceptor and Spinal Cord Molecular Signature Center is a consortium within the NIH PRECISION Human Pain Network. The Center aims to fundamentally advance the understanding of the molecular neurobiology and neuroimmunology underlying human neck and low back pain, thereby enabling the discovery of therapeutic targets. We are pursuing this aim by applying bulk, single cell and spatial transcriptomics to tissues recovered from patients with neck and low back pain undergoing C1-2 and lumbar arthrodesis. The C2 dorsal root ganglion, facet joints, muscles, fascia, and intervertebral discs are harvested; control tissues are obtained from organ donors. A critical advantage of human research is the study of molecular neurobiological mechanisms in the context of the phenotypic complexity of chronic pain. The aim of this article is to summarize the rationale and methods used in our project to phenotype patients.

Methods: Phenotyping domains include pain-related characteristics such as pain intensity, duration, and location; physical function; psychosocial function; neuropathic components assessed by self-report and quantitative sensory testing; somatosensory functions such as mechanical pain sensitivity and temporal summation; and radiological findings.

Conclusion: We anticipate that comprehensive phenotyping will greatly facilitate the identification of phenotype-specific transcriptional signatures associated with chronic neck and low back pain, revealing new neurobiological and/or neuro-immunological mechanisms of painful diseases.

Keywords: Low back pain; Neck pain; Phenotyping; RNA-sequencing.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michele Curatolo is chief medical officer of and holds equity in 4E Therapeutics, and has received research grants from Merck and The National Institutes of Health. Cathryn Payne has nothing to declare. Abby P. Chiu has nothing to declare. Nguyen T. Tran has nothing to declare. Natalie Yap has nothing to declare. Christoph P. Hofstetter is a consultant for Joimax, Globus, Medtronic, and Kuros Biosciences. CPH receives royalties from Globus. CPH received research grants from the Department of Defense and The National Institutes of Health. Joseph B. Lesnak has nothing to declare. Asta Arendt-Tranholm has nothing to declare. Theodore J. Price is a co-founder of and holds equity in 4E Therapeutics, Nuvo Nuro, PARMedics, Nerveli, and Doloromics. T.J.P. has received research grants from AbbVie, Eli Lilly, Grunenthal, Evommune, Hoba Therapeutics, and The National Institutes of Health. Jeffrey G. Jarvik reports grants from NIH/NIAMS; Springer Publishing: Royalties as a book co-editor; GE Healthcare for the Comparative Effectiveness Radiology Research Academic Fellowship (CERRAF): Travel reimbursement for Faculty Board of Review; Wolters Kluwer/UpToDate: Royalties as a chapter author. Judith A. Turner has nothing to declare.

Figures

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