Indications, Imaging, and Technique for Basivertebral Nerve Ablation and Low Back Pain

Educational Objectives

The goal of this program is to improve treatment of chronic low back pain (LBP). After hearing and assimilating this program, the clinician will be better able to:

1. Identify patients experiencing vertebrogenic LBP.
2. Recognize the contributions of anatomy, vasculature, and innervation of vertebral endplates, including the basivertebral nerve (BVN), to chronic LBP.
3. Distinguish among the different types of Modic changes in the vertebral bone using imaging techniques and clinical presentation.
4. Relate Modic changes to responses observed on provocative discography.
5. Evaluate the efficacy and safety of BVN ablation in patients with chronic LBP.

Summary

Vertebrogenic low back pain (LBP): LBP is typically axial and localized, with intermittent flaring and improvement over time; severe pain can last for several years; worsening pain or increasing flare frequency can indicate disk degeneration with evident MRI changes; pain emanates from the endplates; ≈84% of adults experience LBP at some point in their lifetime; chronic LBP affects 10% to 13% of the population in the United States; the most common cause of activity limitation in patients <45 yr of age; in the past, few treatment options were available; 85% of patients seen in primary care have nonspecific LBP; historically, chronic LBP has been associated with disk degeneration (discogenic back pain), which is attributed to inflammatory changes affecting nerves around the posterior annulus

Vertebral endplates: the vertebral endplates surrounding a disk have been implicated as additional potential pain generators; Lotz et al describes endplates as “interfaces between rigid vertebral bodies and pliant intervertebral disks”; because the lumbar spine carries significant forces, and disks lack a dedicated blood supply, the endplates must balance conflicting requirements of adequate strength to prevent vertebral fracture and sufficient porosity to facilitate transport of nutrients to the disks; lumbar compressive forces range from ≈800 N when standing upright to >3000 N during active lifting, with the vertebral body supporting ≈80% of this load; endplates are part of the vertebral body and are particularly susceptible to damage

Structure and development of endplates: endplates consist of a bilayer of bone and cartilage; cartilaginous vertebrae begin to form during the sixth week of prenatal development; they later ossify, starting at the center, leading to separation from the disk by a layer of columnar cartilage which progressively thins until 18 yr of age, when a subchondral bone plate forms, creating a mature endplate; the cartilage consists of collagen fibers aligned parallel to the ends of the vertebral bodies; the bony component consists of a thick, porous layer of trabecular bonethat forms a primary pathway for nutrient transport between the vertebral capillaries and cells within the disk nucleus; small molecules move through the disks primarily via diffusion, and some of the larger molecules can be influenced by flow created by mechanical disk compression and axial load, achieved with daily physical activity; studies assessing the effects of dynamic compression on disk biosynthesis rates, particularly mRNA expression, have shown that dynamic compression is essential for disk health (eg, increases biosynthesis rate, cell viability, mRNA expression)

Degeneration of endplates: the cartilage component gradually thins and calcifies; water and type 1 collagen contents decrease; usually, the endplates deteriorate outward from the center, the weakest part, which lacks a trabecular network for nutrient diffusion; lack of disk stress uniformity influences endplate degeneration, altering mechanical load and influencing structure

Endplate innervation and pain generation: studies demonstrate the presence of sensory fibers in endplates; disk innervation is restricted to the outer layers of the annulus; in contrast, vertebrae and vertebral endplates are well innervated; periosteum is the most densely innervated component; an increase in endplate nociceptor density is observed near areas of disk degeneration; some studies have shown that vertebral endplates have a higher density of nociceptors than the disk; a study by Freemont shows that vertebral endplate nerves are typical pain nerve fibers (demonstrate nociceptive markers, including substance P, high-affinity nerve growth factor, and tropomyosin receptor kinase A [receptor TrkA]); smaller-diameter nociceptor nerve fibers travel to the larger-diameter nerve fibers, which travel to the spinal cord and brain, causing pain; nociceptors on the endplates trace back to the BVN

Provocative discography (PD): gold standard for diagnosis of discogenic pain; a needle is inserted into the intervertebral disk under fluoroscopic guidance; contrast is slowly injected while monitoring injection volume, disk pressure, contrast distribution, and pain response; a positive response is based on pain intensity and concordance with the patient’s typical pain; a control level can increase the diagnostic likelihood of pain emanating from the disk; general specificity is 94%; increases in volume and pressure stimulate nociceptors within the outer annulus, proving the disk is the source of pain; endplate nociceptors also may be stimulated; Heggeness et al (1993) found that endplates deflect comparably to the annulus

Modic changes: bone marrow lesions (ie, signal changes) in the vertebral bone extending from the endplates seen on MRI and classically associated with LBP; Modic type I — represent fibrovascular replacement; demonstrate decreased signal intensity on T1-weighted magnetic resonance imaging (MRI) and increased signal on T2-weighted MRI; histopathology demonstrates vascularized granulation tissue within the adjacent marrow, a marker of inflammation; can convert to type II changes; Modic type II — represent chronic fatty replacement of the marrow surrounding the endplates; bright on T1 and T2-weighted MRIs; Modic type III — indicate bony sclerosis, secondary to the replacement of marrow elements by dense, woven bone within the vertebral body; T1 and T2-weighted MRIs show decreased signal; the most chronic changes; unlike disk degeneration, Modic changes are uncommon in asymptomatic individuals

Study data: following a study by Kjaer et al (2006), the authors concluded that degenerative disk disease without Modic changes is generally asymptomatic, while degenerative disk disease with Modic changes is painful; studies show that patients with disk degeneration and Modic changes experience a higher incidence of pain, compared with patients without Modic changes; data from other independent studies suggest that Modic types I and II changes are among the most specific of all MRI observations for predicting a positive response to PD; results from one of the largest studies, conducted by Thompson et al (2009), reveal that the positive predictive value for positive response to PD is highest among patients with Modic I changes; a study involving patients undergoing lumbar surgery and given only local anesthesia concludes that direct mechanical stimulation of the vertebral endplate correlates most strongly with severe pain; disk denervation or excision provides only modest success in treating axial LBP, suggesting the contribution of other factors

Basivertebral nerve: a study by Antonacci et al, in which 69 vertebral bodies were examined, demonstrates that the nerve in the endplate originates from the BVN; the BVN is an intraosseous nerve that is a branch of the sinuvertebral nerve; it enters each vertebra via the posterior neurovascular foramen and lies within the basivertebral foramen; a major source of afferent vertebral and endplate innervation; afferent nociceptors travel from the endplates and converge posterior to the center of the vertebral body before tracing back to the sinuvertebral nerve, spinal canal, and spinal cord.

Niv et al (2003): the degree of pain relief following vertebroplasty is highly unlikely to be related to bone reinforcement; immediate postsurgical relief is often reported, which suggests a denervation response (ie, the area of bone covered with cement during the procedure may carry some BVN fibers)

Thermal radiofrequency ablation (RFA) of the BVN: a case series by Becker et al (2016) assessed the efficacy of BVN ablation using an intraosseous BVN ablation system to treat 16 patients with ≥6 mo of axial LBP nonresponsive to ≥3 mo conservative care; diagnosis was based on clear evidence of type I or II Modic changes or on PD; at 6-wk follow-up, a decrease in mean Oswestry Disability Index (ODI) score was noted, with improvement persisting for 12 mo after ablation; scores on a 100-point visual analogue scale (VAS) had decreased from 61 to 38 at 6 wk

Setup: typically performed under general anesthesia or conscious sedation; a transpedicular approach is used to access the BVN; the patient is anesthetized and prepped while prone; 2 C-arms (preferred), or a C-arm with a double head, are used to mitigate risk from frequent changes between anteroposterior (AP) and lateral imaging

Trocar placement: the goal is to advance the trocar through the pedicle and dock the ablation device within the vertebral body at the expected location of the BVN; the pedicle is lined up using imaging guidance; the trocar is aimed at the superolateral aspect of the pedicle, and a small incision is made before insertion; the introducer cannula is inserted and pressed inward until it docks on the bone; the trocar is hammered into the bone, using intermittent fluoroscopy to obtain images from multiple angles to ensure a safe trajectory, being careful to avoid significant medial or lateral movement; small hammering movements are performed until the trocar advances through the pedicle (on the medial aspect of the pedicle [AP view] and in the posterior aspect of the vertebral body [lateral view]); as the patient population for BVN ablation is typically younger than that for kyphoplasty or vertebroplasty, bone is denser; greater force is needed to penetrate the pedicle, which increases the importance of sedation

BVN access: after reaching the vertebral body, the needle should be in the medial aspect of the pedicle and at the back of the vertebral body on both imaging views; the BVN is found within the middle of the vertebral body, 30% to 50% past the posterior aspect; to facilitate reaching the BVN, a curved device is then inserted into the introducer cannula; the radiopaque tip of the cannula facilitates positioning; on the AP view, and from a craniocaudal and mediolateral perspective, the needle tip should be in the middle of the vertebral body; on the lateral view, the needle tip should be 30% to 50% deep within the vertebral body

Ablation and completion: once positioning is achieved, the ablation probe is inserted and activated; the temperature of its tip is maintained at 85°C for 15 min to create a 1-cm spherical lesion within the vertebral body; temperature maintenance can be difficult, given high impedance, due to a multitude of factors; when impedance is high, the probe is removed, cleaned, and reinserted to facilitate the burning process; the equipment is removed when the burn is completed; the surgical site is sealed using a hydrocolloid dressing (eg, Cutinova, DuoDERM, RepliCare) or sutures; patients are discharged the same day and experience temporary localized soreness; as endplates with Modic changes are typically at 2 vertebral levels (eg, L4 and L5), 2 BVN ablations typically are required

RFA for vertebrogenic LBP (SMART study; Fischgrund et al, 2018): a prospective, randomized, double-blind, sham-controlled, multicenter study, which evaluated the safety and efficacy of intraosseous thermal RFA for treatment of chronic axial LBP; included patients with type I or II Modic changes, with chronic axial pain unresponsive to 6 mo of nonoperative pain management; treatment was limited to 2 to 3 consecutive vertebral body levels between L3 and S1; exclusion criteria (ie, radicular pain, previous lumbar spine surgery, symptomatic spinal stenosis, osteoporosis, disk extrusion or protrusion >5 mm, spondylolisthesis >2 mm, 3+ Waddell signs, or Beck Depression Inventory score >24) maximized the probability that pain was vertebrogenic; group assignment was made following induction of anesthesia; patients in the treatment arm underwent BVN ablation; patients in the sham arm underwent the same operating room protocol but only simulated thermal ablation; to maintain blinding, patients were treated by one physician and followed by another; at 1 yr, patients in the sham arm were permitted to cross over to the treatment arm

Results: the primary end point was the change in ODI at 3 mo; VAS, radiographic assessment, and patient improvement also were used to evaluate secondary outcomes; targeting success (ie, the degree of overlap of the ablation lesion with the expected area of the BVN at each level treated) was separately assessed via postablation MRI and seen in 89.5% of patients, resulting in division of this group into 2 cohorts (a per-protocol treatment group and a group with unsuccessful targeting); the patients were followed at 3, 6, and 12 mo, primarily looking at the ODI at 3 mo; at 3 mo after treatment, the intention-to-treat group exhibited a 19-point improvement in ODI, meeting the minimal clinically accepted important difference of 10 to 15 points, compared with 15.4 points in the sham group; the per-protocol treatment group had 20.5-point improvement; the difference between the treatment and sham arms was statistically significant; 75.6% of patients in the treatment arm exhibited success (ie, 10 points of improvement in ODI) vs 55.3% of patients in the sham arm

Follow-up at 6 mo and 12 mo: the difference in pain improvement between the arms was statistically significant, with significant improvement in pain and function in the treatment arm; a profound placebo effect was observed in the sham arm, which is typical of procedures that require time in the operating room and sedation

Adverse events: 6 procedural events, including 2 among patients in the sham arm; there were 2 cases of lumbar radiculopathy and 1 case of retroperitoneal hemorrhage; MRI evaluation at 6-wk and 6-mo intervals found no evidence of spinal cord abnormality, avascular necrosis, accelerated disk degeneration, new development of Modic changes, or similar adverse findings

Conclusions and long-term follow-up: BVN ablation in the treatment arm decreased the mean ODI by twice the minimum clinically important difference, in line with the decrease in ODI previously observed following fusion and total disk replacement; ODI improvement at 3 mo in the sham arm is attributed to the positive response to placebo (sham) treatments often seen in patients with chronic pain; the study supports BVN ablation as a minimally invasive treatment for relief of chronic LBP; at 1-yr follow-up, 76.4% of the treatment arm sustained improvement in the ODI; using 20-point improvement, 48% of patients demonstrated a clinically important difference in ODI; at 5-yr follow-up, ODI score improved by 26 points, with improvement in VAS by 4.4 points; confounding factors include patient self-improvement over time and unblinding

Intraosseus BVN ablation vs standard care (Khalil et al, 2019): a prospective, parallel, randomized, controlled, open label, multicenter trial of 140 patients with suspected vertebrogenic LBP; standard care varied (left to the clinician’s discretion) and included pain medication, physical therapy, exercises, chiropractic care, acupuncture, or injections; the original intent was to follow patients for 24 mo, starting at 6 wk, then intermittently at 3, 6, 9, 12, and 24 mo, with a main end point of ODI at 3 mo; a preplanned interim analysis at 3 mo found a profound difference between the groups; consequently, an independent data management committee recommended halting study enrollment to allow for early crossover; ODI at 3 mo revealed mean change from baseline of 23.7 points in the ablation arm, compared with 4.6 points in the standard care arm; using a 15-point ODI change, a 70% responder rate was reported for the ablation arm, compared with 20% in the standard care arm; pain scores decreased by 3.5 points in the ablation arm, compared with 1.1 points in the standard care arm; at 12 mo, the treatment arm reported, on average, 25.7 points improvement in ODI and 2.9-point improvement in pain score; results reveal robust statistical superiority of BVN ablation over standard care; effect size is also profound, compared with other treatment modalities

Readings

Antonacci MD, Mody DR, Heggeness MH. Innervation of the human vertebral body: a histologic study. J Spinal Disord. 1998; 11(6):526-531; Becker S, Hadjipavlou A, Heggeness MH. Ablation of the basivertebral nerve for treatment of back pain: a clinical study. Spine J. 2017 Feb;17(2):218-223. doi: 10.1016/j.spinee.2016.08.032. Epub 2016 Sep 1. PMID: 27592808; Chan SC, Ferguson SJ, Gantenbein-Ritter B. The effects of dynamic loading on the intervertebral disc [published correction appears in Eur Spine J. 2011 Nov;20(11):1813]. Eur Spine J. 2011;20(11):1796-1812. doi:10.1007/s00586-011-1827-1; Fischgrund JS, Rhyne A, Franke J, et al. Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study. Eur Spine J. 2018; 27(5):1146-1156. doi:10.1007/s00586-018-5496-1; Fischgrund JS, Rhyne A, Franke J, et al. Intraosseous Basivertebral Nerve Ablation for the Treatment of Chronic Low Back Pain: 2-Year Results From a Prospective Randomized Double-Blind Sham-Controlled Multicenter Study. Int J Spine Surg. 2019;13(2):110-119. Published 2019 Apr 30. doi:10.14444/6015; Fischgrund J, et al. SMART Clinical Study: Surgical Multi-center Assessment of RF Ablation for the Treatment of Vertebrogenic Back Pain - Full Text View - ClinicalTrials.gov. Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT01446419#moreinfo. Published 2016. Accessed January 13, 2022; Fischgrund J, et al. Five-Plus Year Follow-Up of SMART Randomized Controlled Trial - Full Text View - ClinicalTrials.gov. Clinicaltrials.gov. https://www.clinicaltrials.gov/ct2/show/NCT03997825. Published 2022. Accessed January 13, 2022; Fischgrund JS, Rhyne A, Macadaeg K, et al. Long-term outcomes following intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 5-year treatment arm results from a prospective randomized double-blind sham-controlled multi-center study. Eur Spine J. 2020;29(8):1925-1934. doi:10.1007/s00586-020-06448-x; Freemont AJ, Watkins A, Le Maitre C, Baird P, Jeziorska M, Knight MT, Ross ER, O'Brien JP, Hoyland JA. Nerve growth factor expression and innervation of the painful intervertebral disc. J Pathol. 2002 Jul;197(3):286-92. doi: 10.1002/path.1108. PMID: 12115873; García-Cosamalón J, del Valle ME, Calavia MG, et al. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J Anat. 2010; 217(1):1-15. doi:10.1111/j.1469–7580.2010.01227.x; Heggeness MH, Doherty BJ. Discography causes end plate deflection. Spine (Phila Pa 1976). 1993;18(8):1050-1053. doi:10.1097/00007632-199306150-00015; Khalil JG, Smuck M, Koreckij T, et al. A prospective, randomized, multicenter study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain. Spine J. 2019; 19(10):1620-1632. doi:10.1016/j.spinee.2019.05.598; Kjaer P, Korsholm L, Bendix T, Sorensen JS, Leboeuf-Yde C. Modic changes and their associations with clinical findings. Eur Spine J. 2006;15(9):1312-1319. doi:10.1007/s00586-006-0185-x; Liu J, Huang B, Hao L, et al. Association between Modic changes and endplate sclerosis: Evidence from a clinical radiology study and a rabbit model. J Orthop Translat. 2018;16:71-77. Published 2018 Aug 17. doi:10.1016/j.jot.2018.07.006; Lotz JC, Fields AJ, Liebenberg EC. The role of the vertebral end plate in low back pain. Global Spine J. 2013; 3(3):153-164. doi:10.1055/s-0033-1347298; Macadaeg K, Truumees E, Boody E, et al. A prospective, single arm study of intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: 12-month results. North American Spine Society Journal. 2020; 3: 100030. doi.org/10.1016/j.xnsj.2020.100030; Niv D, Gofeld M, Devor M. Causes of pain in degenerative bone and joint disease: a lesson from vertebroplasty. Pain. 2003;105(3):387-392. doi:10.1016/S0304-3959(03)00277-X; Skórzewska A, Grzymisławska M, Bruska M, et al. Ossification of the vertebral column in human foetuses: histological and computed tomography studies. Folia Morphol (Warsz). 2013; 72(3):230-238. doi:10.5603/fm.2013.0038; Thompson KJ, Dagher AP, Eckel TS, Clark M, Reinig JW. Modic changes on MR images as studied with provocative diskography: clinical relevance--a retrospective study of 2457 disks. Radiology. 2009;250(3):849-855. doi:10.1148/radiol.2503080474.

Disclosures

Dr. Barrette reported nothing relevant to disclose. The planning committee reported nothing relevant to disclose. In his lecture, Dr. Barrette presents information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Barrette was recorded exclusively for Audio Digest on May 13, 2021, using teleconferencing software, in compliance with social-distancing guidelines during the COVID-19 pandemic. Audio Digest thanks Dr. Barrette for his cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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Lecture ID:

OR450301

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This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.