A Phase 4 interventional study of Normal saline infusion and Naloxone infusion in Low Back Pain and Zygapophyseal Joint Arthritis, sponsored by Middle Tennessee Research Institute. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-18.
Sponsored by Middle Tennessee Research Institute · Phase 4, Interventional, and Diagnostic
This study will study pain relief after spine injections that are used to guide care. Some improvements in pain from a procedure might be from placebo effect rather than the physiological effect of the procedure. The study will use naloxone to reverse the effect of the body's internal placebo system after a spine injection, so the placebo effect and the injection effect can be measured separately. This process may improve the understanding of spine injections and their ability to guide pain care.
Nerve blocks are commonly used in pain medicine to diagnose painful conditions and predict response to invasive procedures and surgeries. Placebo responses may cripple clinicians' ability to interpret responses to nerve blocks and guide patient care, when reported pain relief is due to placebo rather than the nerve block.
Existing methods to assess placebo response in clinical practice are limited and indirect. The area that is most explored is in the diagnosis of pain from the facet joints of the spine and relies on an indirect signal from repeated diagnostic injections.
Lumbar medial branch radiofrequency neurotomy (LMBRN) is commonly used to treat low back pain and can lead to large improvements in pain and disability. There is a high failure rate of LMBRN even after a series of controlled prognostic injections called lumbar medial branch nerve blocks (LMBB) with local anesthetic. The discrepancy between response to LMBB and LMBRN has been attributed to the confounding of pain relief from the nerve block with pain relief from the placebo response.
Endogenous opioids (EO), substances produced within the human body that bind to opioid receptors and produce opioid analgesia, are likely responsible for most of the placebo response caused by LMBB.
This study will use naloxone, an opioid receptor antagonist, to completely block the activity of EOs in patients. First, the pain relief after LMBB will be recorded - this is a combination of the effect of the nerve block and EO released in the placebo response. Normal saline will be infused, as an internal control for the state of receiving an infusion. Naloxone will then be infused, reversing EO-dependent placebo analgesia - the analgesia remaining will be from the nerve block. Finally, clinical outcomes from LMBRN will be collected to determine whether using naloxone with LMBB can improve prediction of outcomes with LMBRN.
Naloxone will be used to probe a mechanism of procedurally-induced endogenous-opioid mediated placebo analgesia. No IND is pursued in this study.
These data will provide detailed parameters of placebo response from LMBB, improving interpretation of LMBB for estimation of prevalence of zygapophyseal joint pain and for prognostication of LMBRN.
Furthermore, if this methodology of EO reversible analgesia is feasible for investigation of placebo from LMBB, it will be more broadly investigated in diagnostic and prognostic injections used in interventional pain management.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's planned enrollment of 33 is below the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →Middle Tennessee Research Institute is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
This is a single group study. The participants will undergo two sequential experimental conditions: saline infusion and naloxone infusion. Participants will be identified as candidates for standard of care lumbar medial branch block, consented, and enrolled. Baseline demographics and patient reported clinical measures will be collected. All participants will have IV placed, undergo standard of care lumbar medial branch block, wait 20 minutes, then have their response to procedure assessed. Then normal saline will be infused through the IV over several minutes, 10 minutes will pass, and response to procedure re-assessed. Then naloxone will be infused through the IV over several minutes, 10 minutes will pass, and response to procedure re-assessed for a final time. IV will then be removed. Participants will then follow standard of care clinical practice for second lumbar medial branch block and lumbar medial branch radiofrequency neurotomy treatment.
Drug: Normal saline infusion · Drug: Naloxone infusion
After assessment of response to lumbar medial branch block, 8 ml normal saline will be infused through IV over several minutes. 10 minutes will pass, and response to lumbar medial branch block procedure will be re-assessed. After this step, naloxone infusion will occur (see next intervention)
After infusion of normal saline and re-assessment of response to lumbar medial branch block procedure, 8 milligrams of naloxone will be infused over several minutes. Then after 10 minutes, response to lumbar medial branch block procedure will be re-reassessed for the final time.
Endogenous opioid-dependent placebo analgesia
Endogenous opioid-dependent placebo analgesia is defined as change in analgesia after lumbar medial branch block #1 (measured by numeric pain rating scale) after infusing naloxone
Time frame: 10 minutes after naloxone infusion
Saline-reversible analgesia
Saline-reversible analgesia is defined as change in analgesia after lumbar medial branch block #1 (measured by numeric pain rating scale) after infusing saline
Time frame: 10 minutes after saline infusion
Change in low back pain score after Lumbar Medial Branch Block #2
Change in Numeric Pain Rating Scale score for low back pain after Lumbar Medial Branch Block #2
Time frame: Approximately 2 weeks after Lumbar Medial Branch Block #1, and before Lumbar Medial Branch Radiofrequency Neurotomy
Change in low back pain score after Lumbar Medial Branch Radiofrequency Neurotomy
Change in Numeric Pain Rating Scale score for low back pain after Lumbar Medial Branch Neurotomy
Time frame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
Change in McGill Pain Questionnaire-2 after Lumbar Medial Branch Radiofrequency Neurotomy
Change in McGill Pain Questionnaire-2 score after Lumbar Medial Branch Radiofrequency Neurotomy
Time frame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
Change in MQS-III after Lumbar Medial Branch Radiofrequency Neurotomy
Change in MQS-III score after Lumbar Medial Branch Radiofrequency Neurotomy
Time frame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
Change in Patient-Reported Outcomes Measurement Information System-29 after Lumbar Medial Branch Radiofrequency Neurotomy
Change in Patient-Reported Outcomes Measurement Information System-29 score after Lumbar Medial Branch Radiofrequency Neurotomy
Time frame: Baseline, then 6 weeks, 3 months, 6 months after Lumbar Medial Branch Radiofrequency Neurotomy
Fluoroscopy evaluation for procedural integrity - Lumbar Medial Branch Block
Fluoroscopic images of Lumbar Medial Branch Blocks will be collected to document procedural integrity. This measure is a binary (yes,no) describing whether the tip of the procedure needle is in contact with the anatomical target on each of the procedural images.
Time frame: during Lumbar Medial Branch Block procedure
Fluoroscopy evaluation for procedural integrity, distance - Lumbar Medial Branch Radiofrequency Neurotomy
Fluoroscopic images of Lumbar Medial Branch Radiofrequency Neurotomy will be collected to document procedural integrity. This measure is the number of radiofrequency cannula widths between the anatomical target and the radiofrequency cannula.
Time frame: during Lumbar Medial Branch Radiofrequency Neurotomy procedure
Fluoroscopy evaluation for procedural integrity, displacement - Lumbar Medial Branch Radiofrequency Neurotomy
Fluoroscopic images of Lumbar Medial Branch Radiofrequency Neurotomy will be collected to document procedural integrity. This specific measure is the (x,y) coordinates of the proximal and distal ends of the radiofrequency cannula tip minus the (x,y) coordinates of the proximal and distal bounds of the target structure.
Time frame: during Lumbar Medial Branch Radiofrequency Neurotomy procedure
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