Procedural Framing and Epidural Steroid Injection Outcomes

Two hundred and ten eligible individuals will be randomized in blocks of 10 in a 2:2:1 ratio to receive positive framing for ESI (treatment group), neutral framing for ESI (control group), or pharmacological therapy and instructions to exercise (active control group), respectively. There will suballocation based on whether the patient has unilateral or bilateral pain (i.e., whether the participant would receive a transforaminal ESI or an interlaminar ESI, respectively). This is because there may be differences in outcomes (transforaminal injections for unilateral pain may be more effective than an interlaminar injection for bilateral pain), as well as possible differences in side effects.

For the 84 individuals randomized to the study group (positive framing of ESI), the investigators will provide 5 slides with bullet points and images outlining peer-reviewed studies, reviews and guidelines on ESI that present the treatment in a more positive light (consistent with the views of most people who perform ESIs), but still consistent with evidence. These slides will contain references to high-quality articles and there will be an investigator present to answer questions. There is a very wide range in how a procedure is presented to patients, and this framework is consistent with how ESI are presented to patients by pain practitioners from all over the world. This material is all publicly available but has been compiled in presentation form.

For the 84 individuals in the ESI control group, the investigative team will provide a 1-slide overview on ESI that is slightly less optimistic, consistent with how many non-pain-physicians view ESI including that the evidence for surgery reduction is questionable.

For the 42 individuals in the active control group who will receive a first-line medication for neuropathic and non-structured instructions to exercise, the investigators will provide a 1-side overview that presents the raw, neutral facts on adjuvants for sciatica (some guidelines recommend them, others do not, but some recommend a trial of conservative care for back pain before interventions; there are no medications across the globe approved for lumbosacral radiculopathy).

• Behavioral manipulation of ESI expectations (Behavioral): 5-slide summary of ESI portrayed in a positive light, accompanied by a study investigator.
• No behavioral manipulation of ESI expectations (Other): 1-slide summary of ESI portrayed in a neutral light.
• No behavioral manipulation of pharmacotherapy expectations (Other): 1-slide summary of medications for neuropathic pain portrayed in a neutral light.

Primary outcomes

• Mean reduction in average leg pain [4 weeks]: Mean reduction in average leg pain on a 0-10 numerical rating pain scale over the past week. This is the study's primary endpoint. 0=no pain, 10= worst pain imaginable.

Secondary outcomes

• Leg pain at rest [Up to 15 minutes after the procedure]: Leg pain at rest on a 0-10 verbal rating scale while in the recovery area. 0=no pain, 10= worst pain imaginable.
• Leg pain with activity [Up to 15 minutes after the procedure]: Leg pain with walking and bending on a 0-10 verbal rating scale while in the recovery area
• Back pain at rest [Up to 15 minutes after the procedure]: Back pain at rest on a 0-10 verbal rating scale while in the recovery area
• Back pain with activity [Up to 15 minutes after the procedure]: Back pain with activity (walking, bending) on a 0-10 verbal rating scale while in the recovery area
• Patient satisfaction [Up to 15 minutes after the procedure]: Patient satisfaction with ESI on 1-5 Likert scale (1= very unsatisfied, 3= neutral, 5= very satisfied), recorded upon recovery area discharge
• Average leg pain [4 weeks]: Average leg pain on a 0-10 numerical rating scale over the past week
• Average back pain [4 weeks]: Average back pain on a 0-10 numerical rating scale over the past week
• Worst leg pain [4 weeks]: Worst leg pain on a 0-10 numerical rating scale over the past week
• Worst back pain [4 weeks]: Worst back pain on a 0-10 numerical rating scale over the past week
• Oswestry Disability Index (ODI) [4 weeks]: Oswestry Disability Index on 0-50 scale (converted to %), with higher scores indicating greater back pain-related disability
• Hospital Anxiety and Depression Scale (HADS) [4 weeks]: Anxiety and Depression scores (0-21 for each subscale), with higher scores indicating greater disease burden (anxiety and depression)
• Athens Insomnia Scale [4 weeks]: Measure of insomnia scored from 0-24, with higher scores indicating greater sleep dysfunction
• Analgesic medication reduction [4 weeks]: >20% reduction in opioids or cessation of non-opioid analgesic
• Patient global impression of change (PGIC) [4 weeks]: Patient satisfaction with ESI on 1-7 Likert scale (1= no change, 3= a little better, 4= somewhat better 5= moderately better, 7= a great deal better)
• Positive categorical outcome [4 weeks]: >/=30% reduction in average leg pain (or worst leg pain if average leg pain </=4) with a PGIC >/=4
• Average leg pain [12 weeks]: Average leg pain on a 0-10 numerical rating scale over the past week
• Average back pain [12 weeks]: Average back pain on a 0-10 numerical rating scale over the past week
• Worst leg pain [12 weeks]: Worst leg pain on a 0-10 numerical rating scale over the past week
• Worst back pain [12 weeks]: Worst back pain on a 0-10 numerical rating scale over the past week
• Oswestry Disability Index (ODI) [12 weeks]: Oswestry Disability Index on 0-50 scale (converted to %)
• Hospital Anxiety and Depression Scale (HADS) [12 weeks]: Anxiety and Depression scores (0-21 for each subscale)
• Athens Insomnia Scale [12 weeks]: Measure of insomnia scored from 0-24
• Analgesic medication reduction [12 weeks]: >20% reduction in opioids or cessation of non-opioid analgesic
• Patient global impression of change (PGIC) [12 weeks]: Patient satisfaction with ESI on 1-7 Likert scale (1= no change, 3= a little better, 4= somewhat better 5= moderately better, 7= a great deal better)
• Positive categorical outcome [12 weeks]: >/=30% reduction in average leg pain (or worst leg pain if average leg pain </=4) with a PGIC >/=4

Other outcomes

• Adverse events [10-15 minutes (for ESI)]: Any adverse event or complication
• Adverse events [4 weeks]: Any adverse event, attributed to treatments or not
• Adverse events [12 weeks]: Any adverse event, attributed to treatments or not, at all time points

Sex: All

Inclusion Criteria:

* Age > 18
* Lumbosacral radicular pain based on history and physical exam (e.g. pain radiating into one or both lower extremities, sensory loss, muscle weakness, positive straight leg raising test etc.)
* Duration of pain >6 weeks
* NRS leg pain score >/= 4 (or if 3/10, greater or equal to back pain \& worst leg pain is >/=4)
* MRI evidence of spinal pathology consistent with symptoms
* Candidates for ESI and pharmacotherapy

Exclusion Criteria:

* Untreated coagulopathy
* Previous spine surgery
* No MRI or non-concordant MRI study
* Leg pain > 15 years duration
* Epidural steroid injection within past 2 years
* Signs or symptoms of cauda equina syndrome
* Previous failed trials with gabapentin and pregabalin and tricyclic antidepressants and duloxetine
* Allergic reactions to contrast dye prohibiting injection (e.g., tranforaminal ESI), gabapentinoids, tricyclic antidepressants or duloxetine, and contraindications to all of the above medications
* Referrals from surgery for diagnostic injections for surgical evaluation
* Serious medical (e.g. congestive heart failure) or psychiatric (untreated depression) condition that might preclude optimal outcome
* Pregnancy
* Inability to understand basic English

• Schmidt S, Loef M, Ostermann T, Walach H. Treatment effects in pharmacological clinical randomized controlled trials are mainly due to placebo. J Clin Epidemiol. 2025 Mar;179:111658. doi: 10.1016/j.jclinepi.2024.111658. Epub 2024 Dec 27. PMID 39733973
• Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH. Sham device v inert pill: randomised controlled trial of two placebo treatments. BMJ. 2006 Feb 18;332(7538):391-7. doi: 10.1136/bmj.38726.603310.55. Epub 2006 Feb 1. PMID 16452103
• Sebastian A, Wyld L, Morgan JL. Examining the variation in consent in general surgery. Ann R Coll Surg Engl. 2024 Feb;106(2):140-149. doi: 10.1308/rcsann.2023.0020. Epub 2023 May 23. PMID 37218649
• Kern A, Kramm C, Witt CM, Barth J. The influence of personality traits on the placebo/nocebo response: A systematic review. J Psychosom Res. 2020 Jan;128:109866. doi: 10.1016/j.jpsychores.2019.109866. Epub 2019 Nov 7. PMID 31760341
• Kang H, Miksche MS, Ellingsen DM. Association between personality traits and placebo effects: a preregistered systematic review and meta-analysis. Pain. 2023 Mar 1;164(3):494-508. doi: 10.1097/j.pain.0000000000002753. Epub 2022 Aug 10. PMID 35947877

• Steven P Cohen, MD, Principal investigator, Northwestern University