6.7. Subgroup analysis of periradicular infiltration (V)

The present subgroup analysis revealed that the short-term effect of the steroid treatment was most pronounced for contained herniations and symptomatic lesions situated at the L4–5 (or L3–4) disc level. Patients with a contained herniation were less likely to undergo back surgery when receiving the steroid treatment and they also had significantly fewer days on sick leave from 3 to 6 months. Counter-effectiveness of the steroid treatment was most pronounced for extrusions, where the steroid injection generated significantly higher medical costs and a greater likelihood of surgery. The authors are not aware of any other studies where the response to epidural or periradicular epidural steroids was analyzed according to the type of disc displacement.

Outcome measures in low back research can be divided into disease-specific and generic functional status, or quality-of-life questionnaires (Deyo et al. 1994). The short-term efficacy of the methylprednisolone–bupivacaine injection compared to saline at the L4-5 disc level was evident in disease-specific measures (leg pain, disability by Oswestry, and straight leg raising restriction), whereas in the case of contained herniations efficacy was seen in leg pain and one dimension of the generic questionnaire (NHP). The Oswestry and Million scales have often been employed as outcomes in longitudinal ”pre-post” studies (Kopec & Esdaile 1995), yet the Oswestry disability questionnaire may be less sensitive than the Roland-Morris questionnaire (Bouter et al. 1998). Another possible explanation for the lesser disease-specific effect in the case of contained herniations is the smaller patient number in this subgroup. This could also explain why we found no difference between the treatments in the case of bulges, although an uncontrolled study suggested that foraminal steroids could be effective in this subgroup (Shackleford & Mulholland 1994).

Periradicular infiltration with steroid seemed to prevent surgery in contained herniations, suggesting the effectiveness of steroid treatment in this subgroup. Corticosteroids may calm the inflammatory process in many ways (Cupps & Fauci 1982, Arantes et al 2000). Betamethasone clearly inhibits the secretion of cytokines (IL-1α, IL-1β , IL-6 and TNFα) and PgE₂ from harvested disc herniation tissues in vitro (Takahashi et al. 1996). Local anaesthetic might also exert some beneficial effect, as in the porcine model lidocaine appeared to have an anti-inflammatory effect (Yabuki et al. 1998b). In this study, 42 % of patients with contained herniation underwent surgery after the saline injection, contrasted with 20% after the steroid injection. The operated patients were almost entirely painless after surgery, which may explain the between-group differences in favour of saline at 6 months. For contained herniations repeated steroid injections could be recommended, maybe 2 to 4 weeks after the index injection, as the steroid treatment does not increase the rate of disc operations and is effective in diminishing leg pain.

Macrophages are found in abundance in disc herniations, and are thought to play a role in the resorption of herniations (Ikeda et al. 1996, Haro et al. 1997, Habtemariam et al. 1998). Macrophages are more prominent in extrusions than in non-extruded herniations (Grönblad et al 1994, Haro et al 1996, Matsui et al. 1998, Arai et al. 2000). When extrusions were compared with non-extruded herniations, they exhibited more vascularity (Yasuma et al 1993, Haro et al. 1996, Ikeda et al. 1996) and monocyte chemotactic protein-1 positive cells (Haro et al. 1996). Mononuclear cells infiltrate along the margins of extruded discs, expressing inflammatory mediators. In co-cultures with endothelial cells, disc cells from extrusions enhanced the proliferation of endothelial cells and fibroblasts significantly more than disc cells from protrusions (Doita et al. 1996). It is speculated that the extrusion of herniated nucleus pulposus causes damage to the anulus fibrosus and epidural vessels, inducing fibroblasts and endothelial cells to produce chemokines, which may recruit macrophages in the initiation of the resorption process of disc herniation (Haro et al. 1996). The vascularized granulation tissue can be detected with contrast media (e.g. Gd-DTPA) as rim enhancement along the edges of extrusions (Yamashita et al. 1994). Enhancement is most pronounced in the case of sequesters, and histologically macrophages and small amounts of T-lymphocytes are found (Ikeda et al. 1996). It may be that corticosteroids have some detrimental effect on the function of macrophages. In fact, in a rabbit model high-dose steroid suppressed the replacement of grafted intervertebral disc tissue, in accordance with our results (Minamide et al. 1998). Our subgroup analysis revealed that the steroid injection seemed more harmful for extrusions, which accords with the observation that macrophages are more abundant in extruded disc fragments. While inhibiting the secretion of cytokines (including TNF-a) (Takahashi et al. 1996), steroids may interfere with the resorption of HNP, in which TNF-α plays an important role (Haro et al. 2000). This was clearly seen in our study: steroid and saline were both effective in relieving leg pain, but at approximately 3 months patients in the steroid group were more likely to be operated compared to those in the saline group.

The steroid intervention already produced some monetary savings for contained herniations by 4 weeks, but by 1 year it had saved $1969 per treated patient. The disparity of operation rates in these two subgroups explains the significant differences in medical costs, as well as the decrease in days on sick leave at 6 months among the contained herniation cases treated with steroid. The cost-effectiveness analysis indicates that for contained herniations the steroid treatment was decisively more cost-effective than saline, with a difference of over $12 600 per one painless patient. The contrast might have been even greater with dry-needling as placebo. For extrusions, on the other hand, the cost-effectiveness analysis suggests that a better alternative to saline than steroid needs to be sought, one possibility being a TNF-α antagonist (Olmarker & Larsson 1998). We did not include indirect costs in our economic analysis, because return to work is less responsive to clinical treatment than symptoms or daily functioning, although it is of utmost social and personal importance (Deyo et al. 1998). Moreover, the monetary assessment of work absenteism is controversial (Hutubessy et al. 1999).