Adding steroids to lidocaine in a therapeutic injection regimen for patients with abdominal pain due to anterior cutaneous nerve entrapment syndrome (ACNES): a single blinded randomized clinical trial

1 Introduction

Abdominal wall pain due to anterior cutaneous nerve entrapment syndrome (ACNES) is a potentially debilitating condition that is increasingly recognized in first and second line practices. Patients characteristically complain of one small area of abdominal wall tenderness with typical properties of neuropathic pain such as somatosensory skin disturbances and burning or “electric” sensations [1], [2]. Various treatment options were suggested including injection therapy using local anesthetic agents. Some patients experience a therapeutic effect of one or several peripheral nerve blocks using 5–10 mL of lidocaine [3], [4]. More invasive treatment options are pulsed radio frequency treatment (pRF) or a neurectomy of the anterior cutaneous nerve endings [5], [6].

The ideal therapeutic approach for ACNES is minimally invasive. The addition of corticosteroids to a local anesthetic injection may seem logical if one assumes that ACNES is based upon an entrapment mechanism associated with neurogenic inflammation and ischemia [7]. A previous systematic review investigating the effect of corticosteroids addition compared to lidocaine alone in compression neuropathies showed increased pain reduction in the steroids groups although the analyzed studies were of low quality [8].

The exact mechanism of action of corticosteroids is largely unknown. In general, perineurally administered corticosteroids were found to prolong short term peripheral nerve block analgesia duration with several hours. Moreover, widespread anecdotal evidence suggests that these blocks can exert an effect that largely exceeds the intrinsic half time of corticosteroids and may occasionally result in complete long term pain remission [9], [10], [11], [12], [13]. However, the administration of lidocaine alone can also initiate anti-phlogistic effects leading to long term pain relief [14], [15]. One systematic review found that steroids added to local anesthetics did not confer additional benefits in spinal pain syndromes [16]. In our center it is standard practice to treat an ACNES patient with up to three consecutive infiltrations into the point of maximum pain prior to initiate further invasive treatments such as pRF or a neurectomy [6]. The first infiltration using lidocaine is also used as a diagnostic tool to support the diagnosis. Once confirmed, it is usual care to administer consecutive injections using a mix of lidocaine and corticosteroids.

Currently however, the ideal injection regimen for ACNES is unknown. The present single blind randomized clinical trial was aimed to evaluate the efficacy of corticosteroids addition in ACNES patients receiving lidocaine peripheral nerve blocks for this specific abdominal wall pain syndrome.

2 Materials and methods

This single blind randomized clinical trial was conducted at two Dutch centers: Máxima Medical Center (SolviMáx, Center of Excellence for Chronic Abdominal Wall and Groin Pain), Veldhoven, and Pantein Hospital, Boxmeer. Both hospitals have specialized surgery departments with considerable experience in the treatment of chronic abdominal wall and groin pain syndromes. The Medical Ethics Committee of MMC approved study design, protocol and informed consent procedures. The study was registered in the Dutch Clinical Trial Register (NTR 4141). Design and reporting of this trial were performed according to the CONSORT guidelines [17].

3 Results

Group baseline characteristics were similar as presented in Table 1. Patient flow is presented in Fig. 1. Fifty and fifty-one of two initial allocated groups of 68 patients reached the primary endpoint according to protocol. Reasons for drop-out were similar in both groups as the majority of these patients did not require a second therapeutic injection because one therapeutic or even only a diagnostic injection provided long lasting pain relief. The distribution of these early responders is presented in Fig. 2.

Fig. 1:

Study diagram in ACNES patients receiving injection therapy using lidocaine with (LC) or without (LA) steroids.

Fig. 2:

Effects of injection therapy for ACNES using lidocaine with (LC) or without (LA) steroids.

Both an intention to treat (ITT) and per protocol (PP) analysis were performed. Concerning the primary outcome, the proportion of patients demonstrating a successful response was similar in the LA and LC group (43 and 34%, respectively; p=0.29). Therapeutic success using PP analysis was slightly lower but again no significant group differences were observed (LA: 38% vs. LC: 31%; p=0.61).

At 12 weeks, the number of patients still experiencing pain relief was lower compared to the 6 weeks’ time point (LA: 20% vs. LC: 18%, p=0.80) as shown in Table 2. Patients with pain recurrences between 6 and 12 weeks had undergone additional injections or pRF treatment and were excluded from this analysis.

There were no significant differences in incidence or nature of adverse events between both groups (LA: 23/68, LC: 29/68, p=0.46). Brief increases of pain after injection, temporary pain, tenderness or hematoma at the injection site and malaise were frequently reported. No major adverse events were observed. A multiple regression analysis including group, gender, BMI, age, duration of symptoms, baseline NRS and findings during physical examination showed no significant effect of allocated group on a successful response. A modest effect of younger age and the absence of clear somatosensory disturbances surrounding the point of maximum pain was observed (Table 3).

3.1 Post hoc analysis

The effect of injection therapy in ACNES patients has been well established in a previous study comparing lidocaine to saline injections [3], and reduction in median pain scores in this cohort shows a clinically significant improvement from baseline NRS 7.0 to an NRS of 5.0 at 6 weeks. In designated successful responders, an average improvement of NRS 6.0 to NRS 2.0 was observed. Changes are illustrated in Fig. 3A and B. Again no significant differences were present between groups.

Fig. 3:

A+B Drop in pain level (NRS) at 6 weeks in ACNES patients following two different injection regimens in all patients (A) and designated responders (B).

4 Discussion

This randomized clinical trial demonstrates that corticosteroids do not exert an additional therapeutic effect in the treatment of ACNES as lidocaine alone is equally effective, both in a single and in a multiple injection regimen. The alleged systemic effect of steroids does not confer additional therapeutic success in this particular pain group as demonstrated by the median drops in NRS scores. Interestingly, the observed long term success rate of lidocaine is higher than suggested by anecdotal evidence [18]. The arbitrarily chosen regimen of three consecutive injections appears adequate although a substantial portion of patients required only one injection for sufficient pain relief. The intention to treat analysis that was performed therefore gives an excellent representation of clinical practice and outcomes.

A limitation of this study is the fact that a temporary successful response after a diagnostic lidocaine injection was an inclusion criterium that was deemed necessary to confirm a diagnosis of ACNES [3]. This prerequisite may possibly have preselected a subgroup of patients who would eventually also have a favorable long term response to injection therapy. Current practice in our center is that ACNES is a clinical diagnosis, and a temporary >50% pain reduction following a diagnostic block is currently not considered necessary anymore to explore treatment options other than injection therapy. A response of <50% pain reduction, however, is associated with a slightly less favorable outcome after a final neurectomy procedure [19]. The authors do not expect that non-responders to a diagnostic lidocaine injection will react significantly different to the combination with steroids although caution is required. Moreover, given the fact that the outcome of the corticosteroid group was even slightly worse than the lidocaine only group, it is very unlikely that a type II error has occurred.

The overall success rate of injection therapy is comparable to findings of a previous retrospective case series of 139 ACNES patients reporting that 33% achieved >50% pain reduction after 6 weeks [20]. The lower proportion of patients who still experienced pain relief at 12 weeks strongly suggests, however, that injection therapy is only effective in a small portion of patients (1 in 5). Baseline pain scores, gender, duration of symptoms or BMI did not predict these successful patients, although younger age and lack of clear somatosensory disturbances were possibly associated with a negative outcome. Nonetheless, an “injection therapy first approach” for each new ACNES patient is always worthwhile prior to embarking on more invasive treatments.

Remarkably, the incidence of adverse effects, although minor, was high in both groups. A substantial portion of patients (30–40%) reported increased levels of pain during the first few days following injection that typically subsided after a week. This phenomenon is possibly explained by a volume effect (5–10 mL) on surrounding tissue, or simply by burst stimulation of targeted nerves. Hematomas at the injection site occurred just occasionally. Vague complaints of malaise, although less common in both groups, often coincided with this transient increase in pain suggesting either a vagal response or a systemic effect of both lidocaine and steroids as previously reported [20].

Apart from avoiding potential side effects associated with corticosteroids injection, are there any clinical consequences of omitting these substances from the standard injection therapy for ACNES? Typical local side effects of repeated peripheral steroid injections such as subcutaneous fat necrosis and depigmentation are relatively benign but may pose a cosmetic problem, particularly in young females [21]. Moreover, abolishing steroids from the standard injection therapy in ACNES will have an impact albeit small on the cost-effectiveness of injection therapy although generic corticosteroids are fairly inexpensive.

The findings in this study will possibly contribute to a more evidence based management for pain syndromes including ACNES. A systematic review on the efficacy of perineural steroids for chronic non-cancer pain is currently underway [22]. As mentioned in their trial set up, steroids have been enthusiastically embraced for various pain conditions since their discovery in the 1940s. Because steroids were often standardly combined with lidocaine, there is just no simple way of determining which of the two agents exerts the desired beneficial effects. Lidocaine itself could possibly intervene in the vicious circle of ongoing sensitization that occurs in chronic pain, resetting the neurons’ signaling properties [23]. On the other hand, steroids may possibly decrease ectopic discharge and alleviate edema surrounding injured nerves [24], [25]. The pathophysiological basis underlying the type of pain syndrome will probably determine whether steroids are a valuable addition to injection therapy. For ACNES, however, the authors suggest steroids should be left out of the standard treatment regimen.

5 Conclusion

The addition of corticosteroids to an anesthetic agent for abdominal wall infiltration does not increase the proportion of ACNES patients achieving adequate pain reduction, neither on the short term (6 weeks) nor on the longer term (12 weeks). Injection therapy resulted in an overall clinically significant decrease of pain levels. Lidocaine alone can provide long term pain relief after one or multiple injections in approximately 1 of 5 patients.