Summary
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Low Back Pain would be drug repurposing rather than first-in-human development. This does not mean it is approved for Low Back Pain. ClinicalTrials.gov lists 2 registered trials linking Norepinephrine to Low Back Pain: 1 is currently recruiting; 1 has completed. The most advanced is Phase 4 (NCT05396014). The largest enrolment is 2529 participants (NCT04142177). Registered activity dates to 2022. The literature layer holds 13 publications for this pair: 5 Cochrane reviews, 1 meta-analysis, 1 systematic review, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2010 to 2025. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Low Back Pain ranks 331 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: ~90% of acute LBP episodes resolve within 6 weeks regardless of treatment; chronic LBP (>3 months) shows only 30-40% recovery at 1 year and high recurrence; opioid prescribing correlates inversely with recovery.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 57.5 (trials 7.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 2 total: 1 recruiting, 0 active / not yet recruiting, 1 completed, 0 other |
| Linked publications | 13 (5 Cochrane reviews, 5 clinical trial publications, 1 meta-analysis, 1 systematic review, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRA2C |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT05396014 | The BEST Trial: Biomarkers for Evaluating Spine Treatments 2022 | completed | Phase 4 | 1,014 |
| NCT04142177 | Sequential and Comparative Evaluation of Pain Treatment Effectiveness Response 2022 | recruiting | Not applicable | 2,529 |
Published literature
- Cochrane review Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysisSoliman N, Moisset X, Ferraro MC et al. · The Lancet. Neurology · 2025 · PMID 40252663
- Cochrane review Antidepressants for low back pain and spine-related leg painFerraro MC, Urquhart DM, Ferreira GE et al. · The Cochrane database of systematic reviews · 2025 · PMID 40058767
- Systematic review Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysisAyub S, Bachu AK, Jain L et al. · Frontiers in pain research (Lausanne, Switzerland) · 2024 · PMID 39449766
- Cochrane review PEER systematic review of randomized controlled trials: Management of chronic low back pain in primary careKolber MR, Ton J, Thomas B et al. · Canadian family physician Medecin de famille canadien · 2021 · PMID 33483410
- Clinical trial publication Low back pain in athletes can be controlled with acupuncture by a catecholaminergic pathway: clinical trialArriaga-Pizano L, Gómez-Jiménez DC, Flores-Mejía LA et al. · Acupuncture in medicine : journal of the British Medical Acupuncture Society · 2020 · PMID 32429680
- Clinical trial publication Opioid Exposure Negatively Affects Antidepressant Response to Venlafaxine in Older Adults with Chronic Low Back Pain and DepressionStahl ST, Jung C, Weiner DK et al. · Pain medicine (Malden, Mass.) · 2020 · PMID 31633789
- Cochrane review PubMed record PMID 32338847McDonagh MS, Selph SS, Buckley DI et al. · 2020
- Cochrane review Milnacipran for neuropathic pain in adultsDerry S, Phillips T, Moore RA et al. · The Cochrane database of systematic reviews · 2015 · PMID 26148202
- Meta-analysis Tapentadol for chronic musculoskeletal pain in adultsSantos J, Alarcão J, Fareleira F et al. · The Cochrane database of systematic reviews · 2015 · PMID 26017279
- Clinical trial publication Treating concurrent chronic low back pain and depression with low-dose venlafaxine: an initial identification of "easy-to-use" clinical predictors of early responseRej S, Dew MA, Karp JF · Pain medicine (Malden, Mass.) · 2014 · PMID 25040462
- Clinical trial publication Tolerability of concomitant use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors and oxymorphone extended releasePeniston JH, Hu X, Potts SL et al. · Postgraduate medicine · 2012 · PMID 22437221
- Clinical trial publication Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis painWild JE, Grond S, Kuperwasser B et al. · Pain practice : the official journal of World Institute of Pain · 2010 · PMID 20602712
- Randomized controlled trial Efficacy and safety of duloxetine in patients with chronic low back painSkljarevski V, Desaiah D, Liu-Seifert H et al. · Spine · 2010 · PMID 20461028
Mechanism and notes
Recorded mechanism or class: agonist.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA2C. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Norepinephrine approved for Low Back Pain?
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Low Back Pain would be drug repurposing rather than first-in-human development. This does not mean it is approved for Low Back Pain. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Norepinephrine in clinical trials for Low Back Pain?
ClinicalTrials.gov lists 2 registered trials linking Norepinephrine to Low Back Pain: 1 is currently recruiting; 1 has completed. The most advanced is Phase 4 (NCT05396014). The largest enrolment is 2529 participants (NCT04142177). Registered activity dates to 2022.
What does the evidence show for Norepinephrine in Low Back Pain?
Norepinephrine has both completed registered trials and synthesis-level publications linked to Low Back Pain. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRA2C. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.