Success Rates and Safety of Steroid Injections in Managing Spinal and Sacro-Iliac Pain (CORTisone Injection Spine Study)

This single-centre study will consist of two parts, one retrospective and one prospective with cross-over design, to analyze and summarize the investigators' experience in the evaluation of:

• Efficacy of ultrasonography (US)-guided epidural steroid injections (caudal and interlaminar, compared to transforaminal if performed elsewhere and data available) in patients with lumbar-sacral pain for central spinal stenosis, neuroforaminal stenosis, herniated disc, or failed back surgery syndrome (FBSS);
• Efficacy of cervical, thoracic, and lumbar facet joint and sacroiliac joints (SIJ) injections in patients with nociceptive spinal pain (e.g., osteoarthritis [OA]);
• Spinal levels most frequently affected;
• How frequently a pain presenting as sciatica is actually due instead to hip OA, trochanter pain, bursitis, or SIJ pain, rather than spine pathology.

In this study, the investigators will include at least 100 patients per part with lumbar spinal pain due to lumbar canal stenosis, herniated discs or FBSS (lumbar radiculopathy), treated with caudal or interlaminar epidural steroid injections through different protocols, all under US guidance. In addition, the investigators will examine different administration protocols, including the following injections: facet joints (100 each for cervical and lumbar pain, and as many as possible for thoracic) and/or SIJ (100), compared with injections of local anesthetics only, with Marcaine or Sensorcaine (bupivacaine) or Xylocaine (lidocaine), or oral low-dose naltrexone (spinal radiculopathy).

Comparing these interventions through rigorous research, the study may provide healthcare professionals with refined treatment guidelines, optimized patient care pathways, and ultimately improve outcomes and quality of life for individuals living with chronic back pain. This research could benefit current patients and contribute to the broader knowledge in pain management, guiding future advancements in the field.

The primary objectives of this study are to determine:

• The short-term pain relief response: the difference between pre- and post-treatments based on numeric rating scale (NRS) scores at 1 and 2 weeks;
• The long-term pain relief response, by examining the results of pain relief expressed as magnitude (percentage) and duration (in days) in patients receiving different injections, combined in the integral of pain relief (IPR) scores (IPR = percentage of relief * number of days of relief), and the patient's global impression of change (PGIC), a 7-point word scale describing the improvement or worsening of pain after a treatment, after 4, 6, 8, and 12 weeks, and at 6 and 12 months if possible;
• The patient's functional disability pre- and post-treatment at the same time points, using the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference/Intensity tool and the functional IPR (fIPR), for more or less detailed different grades of improvement assessments. The fIPR will be obtained as a measure of overall improvement in daily functioning (e.g., walking, hygiene, housekeeping, ability to work or study, fatigue, sleep, mood, leisure), as a percentage, and its duration. The degree of pain interference with daily activities, on a scale from 0 to 10 or percentage, will also be examined.

The secondary objectives of this study are to assess:

• Differences in efficacy between different types of steroids (triamcinolone, methylprednisolone, betamethasone, and dexamethasone), and their dosages, and between steroids and local analgesics only;
• The types, number, and severity of side effects;
• Potential genetic mechanisms underlying variable responses to the four corticosteroids (and the respective doses employed) in terms of both efficacy and safety/adverse reactions. Variations in the cytochrome P450 gene CYP3A4 will be examined, as this enzyme is responsible for an established metabolic pathway common to all four agents. Additionally, variations in a related metabolic gene (CYP3A5) and a drug transporter gene (ABCB1) will also be explored as they both have considerable substrate overlap with CYP3A4.
• The effect of different injection locations (caudal or interlaminar, central or directed to the affected side) on pain relief, including the reduction rate of opioid or other medications, like medical or recreational cannabis;
• Independent variables that may impact efficacy and safety of pain relief, including age, sex, body mass index (BMI), occupation, duration of chronic pain (years), anticoagulant medications, chronic kidney disease (CKD, stage 2-4), hypertension, diabetes, osteoporosis, fibromyalgia, cataract, glaucoma, smoking and alcohol consumption, post-surgery period, advanced age (> 90 years);
• The history of pain medications and their change after the injections;
• Bone mineral density (BMD) before and after steroid injection (if available) to examine the hypothesis of injectable steroids reducing bone density and posing a risk for osteoporosis;
• Safety and efficacy of oral low-dose naltrexone in patients who are eligible to receive this medicine (in doses of 1-9 mg, with effects usually noticeable after 1-3 months of use), of different types and doses of steroids in patients who received epidural or intraarticular injections, and of lidocaine infusions for low back pain (LBP) in patients with sciatic pain;
• Frequency of sciatic and SIJ, IT bursa, trochanteric, and hip joint pain in patients with LBP;
• Validity of the fIPR to evaluate patients with spinal pain and their functionality, with possible differences due to pathogenesis/localization (stenosis, disc herniation, facet joints and SIJ OA);
• The possible influence of changes in body weight on the treatment efficacy of US-guided injections or pain in general;
• Prognostic value or meaning of the feeling of pressure on the leg during the injection, as reported by some patients.
• Other potential sub-analysis of different factors that may emerge as relevant.

Inclusion criteria

• >18 years of age;
• Diagnosis of lumbar, cervical, or thoracic pain with various etiologies;
• Eligibility to receive steroid injections for back pain, including epidural, facet joints, or SIJ injections, or other injections (e.g., local anesthetics);
• Being willing and able to provide NRS pain ratings and PROMIS functionality ratings before the intervention, and the same scores plus IPR, fIPR, and PGIC at various follow-up points after the intervention;
• Provide written informed consent.

Exclusion criteria

• Diagnosis of dementia, Parkinson's disease or other cognitive impairments;
• Congenital or acquired polyneuropathy;
• Back surgery in the month before injection treatment or planned surgery in the subsequent 3 months;
• Any clinically significant acute or chronic medical condition that in the judgment of Investigator may preclude injection in the epidural space or compromise patient safety, limit patient's ability to complete the study, and/or compromise the objectives of the study;
• Participation in any other competing clinical study within 3 months prior to screening and during the study period.