We are grateful to Dr. Tobinick for his clinical work evaluating etanercept for spinal pain, and his astute and prescient comments regarding our past and future endeavors.1
First, we would like to point out that intradiscal tumor necrosis factor-α administration to relieve radicular pain is not quite analogous to the intradiscal injection of corticosteroid, which has been shown in previous studies to be no more effective than placebo for this condition.2,3
Although inflammatory cytokines released from a degenerative disc might be the source of a painful, chemically irritated nerve root,4–6
the disc itself is not the primary site of inflammation. Therefore, it is not surprising that intradiscal steroids are ineffective for lumbosacral radiculopathy. For predominantly axial low back pain presumed secondary to internal disc disruption, there is no scientific basis to suppose that the epidural injection of tumor necrosis factor-α inhibitors might be effective.
In contrast, the “mechanistic-based treatment of pain” paradigm advocates identifying the principal pain generator (i.e.
, high concentrations of tumor necrosis factor α expelled from a degenerated disc) and treating it with target-specific medications (i.e.
, tumor necrosis factor-α inhibitors).7
In this context, injecting etanercept intradiscally can be viewed as a logical extension of this theory.
Second and perhaps more importantly, Dr. Tobinick seems to have overlooked the possibility that our intradiscal study was never intended to be the decisive word on the subject. Rather, our main objectives in undertaking this endeavor were to establish safety (hence our low, logarithmically increasing doses) in this setting and to determine dose ranges for the more definitive and auspicious epidural study he alluded to. The risk:benefit ratio is considerably higher for the epidural administration of etanercept in radiculopathy, a condition for which effective treatments are available, than it is for refractory low back pain patients already scheduled to undergo discography in a last-ditch effort to determine eligibility for either experimental intradiscal procedures or spine surgery. In addition, we have previously demonstrated that a significant portion of intradiscal injectate extravasates into the epidural space in patients with degenerative disc disease.8
This suggests that the poor response of our patients may better reflect their long duration of pain (inflammatory cytokines play a more prominent role in acute pain than chronic pain) and multiple previous treatment failures, rather than the intradiscal route of administration.
Steven P. Cohen, M.D.,*
Daniel Wenzell, M.D.,
Thomas M. Larkin, M.D.
*Johns Hopkins School of Medicine, Baltimore, Maryland, and Walter Reed Army Medical Center, Washington, D.C. firstname.lastname@example.org
1. Cohen SP, Wenzell D, Hurley RW, Kurihara C, Buckenmaier CC III, Griffith S, Larkin TM, Dahl E, Morlando BJ: A double-blind, placebo-controlled, dose–response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy. Anesthesiology 2007; 107:99–105
2. Khot A, Bowditch M, Powell J, Sharp D: The use of intradiscal steroid therapy for lumbar spinal discogenic pain: A randomized controlled trial. Spine 2004; 29:833–6
3. Simmons JW, McMillin JN, Emery SF, Kimmich SJ: Intradiscal steroids: A prospective double-blind clinical trial. Spine 1992; 17 (suppl):S172–5
4. Ozaktay AC, Cavanaugh JM, Asik I, DeLeo JA, Weinstein JA: Dorsal root sensitivity to interleukin-1 beta, interleukin-6 and tumor necrosis factor in rats. Eur Spine J 2002; 11:467–75
5. Olmarker K, Larsson K: Tumor necrosis factor (alpha) and nucleus-pulposus-induced nerve root injury. Spine 1998; 23:2538–44
6. Igarashi T, Kikuchi S, Shubayev V, Myers RR: Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology. Spine 2000; 25:2975–80
7. Woolf CJ, American College of Physicians, American Physiological Society: Pain: Moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004; 140:441–51
8. Cohen SP, Oberfell R, Larkin T, Fant G, Stojanovic M: Does needle insertion site affect discography results? A retrospective analysis. Spine 2002; 27:2279–83
© 2008 American Society of Anesthesiologists, Inc.