Low back pain is the leading cause of disability worldwide, affecting 619 million individuals globally in 2020, a number projected to rise to 843 million by 2050 [
1]. The estimated general prevalence of low back pain is 18%, with one-month prevalence of 30% [
2], and lifetime prevalence as high as 84% [
3]. Historically, diagnosing the etiology of low back pain has been challenging, with a widely reported 1,966 study indicating that the cause of low back pain was undetermined in 79% of men and 89% of women in a primary care population [
4]. Importantly, this study was performed prior to the emergence of computerized topography or magnetic resonance imaging (MRI). Given the elusory nature of a low back pain diagnosis—with approximately 85% of primary care low back pain cases considered non-specific [
5]—it is not surprising that outcomes from surgical treatment are often suboptimal [
2].
Modic changes, first described in 1988, are descriptors of abnormal MRI signal change in the bone marrow of the vertebral bodies/endplates [
6], and are seen in 18%–58% of patients with low back pain [
7]. Modic changes are classified into three types: Type 1, the acute/inflammatory phase, characterized by bone marrow edema, is dark on T1 imaging and bright on T2; Type 2, the chronic/fatty phase, marked by fatty infiltration of the bone marrow, is bright on both T1 and T2 imaging; and Type 3, the sclerotic phase, defined by endplate thickening and sclerotic changes, is dark on both T1 and T2 imaging [
6,
8]. Despite being well characterized by MRI signal patterns, the precise etiology of Modic changes remains unclear due to their multifactorial pathophysiology and dynamic nature. Risk factors associated with both the development of Modic changes and conversion between types include male sex, older age, diabetes mellitus, genetic predispositions, obesity, and performing physically demanding work, among others [
8]. While degenerative changes are associated with Modic changes, these MRI findings are more indicative of endplate damage from disc injury [
8].
Although these findings are descriptors of changes in the vertebral bodies, Modic changes were considered to be markers of discogenic low back pain for many decades, with a likelihood ratio of 3.4 indicating “discogenic” pain [
9]. However, a paradigm shift occurred when Modic changes came to be recognized as the imaging correlate of vertebrogenic rather than discogenic low back pain. The discovery that intraosseous nerves traveled with basivertebral vessels throughout the vertebral body provided the anatomical basis that later studies used to determine that, as these vessels supply the vertebral endplates, the accompanying nerves may also innervate them [
10,
11]. This discovery diverted attention towards the vertebral body and endplates as pain generators, leading to a shift from disc-focused to vertebrae-focused treatments for axial low back pain.
The basivertebral nerve originates from the sinuvertebral nerve, enters the vertebral body posteriorly through the basivertebral foramen, and branches to innervate the vertebral endplates [
10,
11]. As the source of pain transmission from the vertebral endplates, this nerve became the interventional target in patients with vertebrogenic low back pain. In 2006, the Intracept
® System (Relievant Medsystems) was developed to deliver radiofrequency energy to the basivertebral nerve via an intraosseous approach (basivertebral nerve ablation, BVNA). In 2011, the U.S. Food and Drug Administration sponsored trials to evaluate safety and effectiveness of BVNA, and a preliminary pilot study yielded positive results. Seventeen patients with greater than six months of vertebrogenic low back pain unresponsive to at least three months of conservative care were enrolled and experienced mean improvement in the Oswestry Disability Index (ODI) from 52 (“severe” disability) to 23 (“moderate” disability) at three-month follow-up which was maintained at one year [
12].
Larger studies followed the initial trials with the key publications occurring in 2018 [
13] and 2019 [
14]. Fischgrund et al. [
13] studied 225 patients with chronic low back pain with Type 1 or Type 2 Modic changes who were randomized to BVNA or sham intervention. The sham intervention consisted of the same preprocedural protocol as BVNA with the “procedure” consisting of docking the introducer cannula only 1–2 mm into the pedicle, providing similar dwell time, and withholding any radiofrequency energy. At three months, the ODI in the treatment arm decreased 20.5 points compared to 15.2 points in the sham arm (p=0.019), and this difference persisted over a 12-month follow-up period. A responder analysis based on an ODI decrease >10 points showed a 75.6% success rate in patients in the treatment group, compared to a 55.3% success rate in the sham group. Despite the high success in the sham group in this trial, the treatment group demonstrated statistically significantly better results. Khalil et al. [
14] carried out a similar study comparing BVNA patients to standard care (including pain medications, physical therapy, exercise, chiropractic treatment, acupuncture, or spinal injections). At three-month follow-up, the mean change in ODI was -25.3 for the BVNA group versus -4.4 points for the standard care group. Given clear statistical superiority, a pre-planned interim analysis performed by a third party concluded that it would be unethical to continue to withhold BVNA from the patients who were randomized to standard care, and early cross-over was offered to these patients. This outcome—prematurely halting a study on the treatment of low back pain because of superior treatment efficacy—is essentially unprecedented in the spine literature.
Other studies have demonstrated similar effectiveness with improvement in pain and disability lasting longer-term. In 2020, Fischgrund et al. [
15] reported their long-term outcomes on 117 patients treated with BVNA with a minimum five-year follow-up. At a mean follow-up time of 6.4 years, ODI improved from 43 to 17 (from “severe” to “minimal” disability), 66% of patients achieved at least a 50% reduction in visual analogue scale pain score, 47% achieved at least a 75% reduction, and 34% achieved complete resolution in their pain at the final follow-up period. Similar findings were noted by Smuck et al. in 2023 [
16] when analyzing two prospective single-arm studies with three-year follow-up intervals. At the three-year end point, there was a mean reduction in ODI of 31.1 points from a 46.1 baseline (again from “severe” to “minimal” disability) and a responder rate based on an ODI improvement >15 points and >50% reduction in numeric pain scores of 69.5%.
Overall, reported complication rates from BVNA have been low. Device- or procedure-related adverse events have ranged from 2.7%–6.7%, with the most common adverse event being mild transient leg pain or paresthesias requiring no further interventions beyond oral medications and resolving within three months after the procedure [
13-
16]. More significant adverse events have included vertebral compression fracture, nerve root injury, lumbar radiculopathy, hematoma formation, and leg pain/paresthesias persisting beyond 6 months, all occurring at rates of less than 2% [
13-
16]. Although rare, procedural errors involving trocar misplacement have directly led to nerve root injury and retroperitoneal hematoma [
13].
Given that this procedure involves passing a trocar through the pedicle to the basivertebral nerve terminus at the midline of the vertebral body, the structures most at risk of injury include the spinal nerves, thecal sac, pedicle, vertebral body, and vertebral vasculature. As a result, measures have been taken to mitigate the risks of fracture and bleeding. Early studies excluded patients with osteoporosis, and the one reported compression fracture in the studies listed above [
13] occurred in a patient with osteopenia. However, vertebrogenic back pain is thought to be underestimated in patients with osteopenia, and this procedure has recently been attempted in these patients [
17]. While the true incidence of post-procedure vertebral body fracture is unknown, it has been reported to be as high as 11% in osteoporotic patients [
18]. Therefore, caution is advised in these patients, and they should be counseled appropriately about potential post-procedure fracture risks. Bleeding risk may be minimized by holding antiplatelet and anticoagulant medications prior to the procedure. However, despite low reported rates of bleeding complications, these risks are not eliminated. The trocar passes through basivertebral vessels as it is moved to the target location, and the lesion is made at the basivertebral nerve terminus where the vasculature also originates. One incident of hematoma formation in the extradural neural axis compartment (posterior to the vertebral body, anterior to the posterior longitudinal ligament) has been reported [
19]. This is an important consideration as hematoma formation could potentially lead to neurologic deficits and account for treatment failures.
Although etiologies for low back pain have been difficult to diagnose historically, research over the last several decades, aided by imaging advancements, has allowed for improved diagnostic accuracy and targeted treatments for a subset of patients. The discovery of Modic changes not only led to increased specificity in determining low back pain etiology, but also provided a new source to target with interventional procedures. In appropriately selected patients, BVNA can result in substantial reduction in pain and disability with low rates of complications.
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