Comparing the Efficacy of Dorsal Root Ganglion Stimulation With Conventional Medical Management in Patients With Chronic Postsurgical Inguinal Pain: Post Hoc Analyzed Results of the SMASHING Study.

OBJECTIVES: Approximately 10% of patients who undergo inguinal hernia repair or Pfannenstiel incision develop chronic (> three months) postsurgical inguinal pain (PSIP). If medication or peripheral nerve blocks fail, a neurectomy is the treatment of choice. However, some patients do not respond to this treatment. In such cases, stimulation of the dorsal root ganglion (DRG) appears to significantly reduce chronic PSIP in selected patients. MATERIALS AND METHODS: In this multicenter, randomized controlled study, DRG stimulation was compared with conventional medical management (CMM) (noninvasive treatments, such as medication, transcutaneous electric neurostimulation, and rehabilitation therapy) in patients with PSIP that was resistant to a neurectomy. Patients were recruited at a tertiary referral center for groin pain (SolviMáx, Eindhoven, The Netherlands) between March 2015 and November 2016. Suitability for implantation was assessed according to the Dutch Neuromodulation Association guidelines. The sponsor discontinued the study early owing to slow enrollment. Of 78 planned patients, 18 were randomized (DRG and CMM groups each had nine patients). Six patients with CMM (67%) crossed over to DRG stimulation at the six-month mark. RESULTS: Fifteen of the 18 patients met the six-month primary end point with a complete data set for a per-protocol analysis. Three patients with DRG stimulation had a negative trial and were lost to follow-up. The average pain reduction was 50% in the DRG stimulation and crossover group (from 6.60 ± 1.24 to 3.28 ± 2.30, p = 0.0029). Conversely, a 13% increase in pain was observed in patients with CMM (from 6.13 ± 2.24 to 6.89 ± 1.24, p = 0.42). Nine patients with DRG stimulation experienced a total of 19 adverse events, such as lead dislocation and pain at the implantation site. CONCLUSIONS: DRG stimulation is a promising effective therapy for pain relief in patients with PSIP resistant to conventional treatment modalities; larger studies should confirm this. The frequency of side effects should be a concern in a new study. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02349659.

Characteristics of 1116 Consecutive Patients Diagnosed With Anterior Cutaneous Nerve Entrapment Syndrome (ACNES).

OBJECTIVE: The aim of this study was to discuss patient history and subjective findings at physical examination in a large case series to validate a proposed comprehensive set of major and minor diagnostic criteria. SUMMARY BACKGROUND DATA: Chronic abdominal pain in some patients is caused by the anterior cutaneous nerve entrapment syndrome (ACNES). ACNES is a clinical diagnosis as no functional testing or imaging modalities are available up to date. METHODS: This study retrospectively analyzed prospectively obtained data from consecutive patients who received the diagnosis ACNES during evaluation at the SolviMáx Center of Excellence for Abdominal Wall and Groin Pain, Eindhoven, The Netherlands, between June 1, 2011 and September 1, 2016. Questionnaires, standard case forms, and digital case files containing characteristics of individuals were used for analysis. RESULTS: Data of 1116 patients suspected and treated for ACNES consistently showed the presence of the following 4 characteristics: sensory disturbances at the painful abdominal area (78%), a positive pinch sign (78%), a positive Carnett's sign (87%), and a positive response to a modified rectus sheath block (>50% pain reduction, 81%). The majority of patients are female of young or middle age with a normal BMI reporting complaints that occurred spontaneously in either a sudden or gradual timeframe, developing a severe (NRS 6-8) chronic abdominal pain that was only diagnosed after a substantial doctor's delay. CONCLUSION: A combination of typical findings in history and physical examination, combined with a positive modified rectus sheath block, may allow for diagnosing ACNES in patients with chronic abdominal pain.

Factors predicting outcome after anterior neurectomy in patients with chronic abdominal pain due to anterior cutaneous nerve entrapment syndrome (ACNES).

BACKGROUND: Chronic abdominal pain due to anterior cutaneous nerve entrapment syndrome may require surgery to provide long-term pain relief in up to 70% of patients. Factors predicting outcome after an anterior neurectomy are unknown. The aim of the study is to identify factors associated with treatment failure to possibly allow for optimizing patient counselling and selection. METHODS: Characteristics of anterior cutaneous nerve entrapment syndrome patients who were unresponsive to nonsurgical therapies and underwent an anterior neurectomy in a tertiary referral center from 2011 to 2016 were analyzed. Treatment failure was defined as <50% pain reduction using a numeric pain rating scale (numeric pain rating score 0-10) approximately 2 months postoperatively. A prediction model based on a multivariate regression analysis was tested for its discriminative value. RESULTS: A total of 495 patients (78% female, median age 40 years, range 8-83) undergoing an anterior neurectomy were eligible for analysis. Pain medication use (odds ratio 1.84, P = .027, confidence interval 1.07-3.17), abdominal surgery in the past (odds ratio 1.85, P = .026, confidence interval 1.08-3.18), the presence of paravertebral tender points at exit points of intercostal nerves (odds ratio 2.58, P = .003, confidence interval 1.39-4.80), and failure to favorably respond to a diagnostic rectus sheath block (odds ratio 3.74, P = .000, confidence interval 3.74 - 7.10) were identified as factors predicting surgical failure. However, a prediction model including these 4 factors had poor accuracy with an area under the curve of 0.64 (confidence interval 0.58-0.70). CONCLUSION: The present study identified risk factors associated with treatment failure that are useful in counseling anterior cutaneous nerve entrapment syndrome patients prior to a surgical intervention.

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.

Background and aims Anterior cutaneous nerve entrapment syndrome (ACNES) may result in chronic abdominal pain. Therapeutic options include local injection therapy. Data on the efficacy of adding corticosteroids to these injections is lacking. Methods Patients ≥18 years with ACNES were randomized to receive an injection of lidocaine with (LC-group) or without (LA-group) the addition of methylprednisolone into the point of maximal abdominal wall pain. Pain was recorded using a numeric rating scale (NRS: 0-10) and a verbal rating scale (VRS: 0=no pain, 5=unbearable pain) at baseline and 6 weeks after the start of a bi-weekly injection regimen consisting of a total of three injections. A minimal 50% reduction on NRS and/or two points on VRS were considered successful responses. Results Between February 2014 and August 2016, 136 patients (median age 46 year, range 18-79, 75% females) were randomized (68 vs. 68). The proportion of patients demonstrating a successful response after 6 weeks did not significantly differ between groups (LA 38%, LC 31%, p=0.61). At 12 weeks, the number of patients still experiencing a minimal 50% pain relief had decreased but no group difference was observed (LA 20%, LC 18%, p=0.80). Minor side effects included temporary increase of pain, tenderness at injection sites or transient malaise (LA23/68, LC 29/68, p=0.46). Conclusions Adding corticosteroids to a lidocaine does not increase the proportion of ACNES patients with a successful response to injection therapy. Lidocaine alone can provide long term pain relief after one or multiple injections, in approximately 1 of 5 patients.

Comparing the efficacy of targeted spinal cord stimulation (SCS) of the dorsal root ganglion with conventional medical management (CMM) in patients with chronic post-surgical inguinal pain: the SMASHING trial.

BACKGROUND: A significant number of patients who undergo a standard inguinal hernia repair or a Pfannenstiel incision develop chronic (> 3 months) post-surgical inguinal pain (PSIP) due to nerve entrapment. If medication or peripheral nerve blocks fail, surgery including neurectomies may offer relief. However, some patients do not respond to any of the currently available remedial treatment modalities. Targeted spinal cord stimulation (SCS) of the dorsal root ganglion (DRG) is a relatively new type of therapy that has a potential to significantly reduce chronic PSIP. The Axium® SCS System (Spinal Modulation Inc., NY, USA) has been shown to be safe and successful in small cohorts of PSIP patients. Aim of this study is to evaluate targeted spinal cord stimulation therapy in patients with PSIP. METHODS: A prospective, multicentre, randomized controlled trial with optional one-way crossover will assess the efficacy of the Axium® SCS system for the treatment of PSIP. Seventy-eight patients with intractable PSIP following open hernia repair or Pfannenstiel incision who did not respond favorably to previous pain treatment regimens including a neurectomy will be randomized to either an Axium® SCS arm or a control arm receiving only conventional medical management (CMM). Primary outcome is the difference in percentage of subjects with ≥50% pain relief after 6 months using a Numerical Pain Rating Scale (NPRS). Data are collected using a daily pain/sleep diary and a number needed to treat (NNT) analysis is performed. Various secondary outcomes will be collected. DISCUSSION: Targeted SCS stimulation of the DRG using the Axium® SCS system will possibly offer significant pain reduction in patients with PSIP who are refractory to other treatment modalities. TRIAL REGISTRATION: The study protocol is registered at the NIH Clinical Trials Registry ( http://clinicaltrials.gov , ClinicalTrials.gov identifier: NCT02349659 ) on January 29, 2015.

DRG Spinal Cord Stimulation as Solution for Patients With Severe Pain Due to Anterior Cutaneous Nerve Entrapment Syndrome: A Case Series.

OBJECTIVES: Anterior Cutaneous Nerve Entrapment Syndrome (ACNES) is a debilitating neuropathic pain condition. A small portion of patients do not respond to any currently available treatment modalities. These patients, often young women, might benefit from targeted spinal cord stimulation of the dorsal root ganglion (DRG). METHODS: This retrospective case series describes five ACNES patients who were referred from a Dutch dedicated tertiary referral center to collaborating sites with extensive experience in DRG stimulation to be implanted with a DRG Axium System (St. Jude/Abbott, IL, USA) in the period of 2013-2016. Numeric pain rating scores at routine 6- and 12-month follow-up visits were analyzed. RESULTS: Three patients experienced >50% pain reduction at 12 months follow-up. Four patients experienced device-related complications, such as lead dislocation, lead breakage, pain at the battery site, and overstimulation. CONCLUSIONS: This case series suggests DRG spinal cord stimulation can be safe and effective for some patients with persistent pain due to ACNES.

Anterior rectus sheath blocks in children with abdominal wall pain due to anterior cutaneous nerve entrapment syndrome: a prospective case series of 85 children.

BACKGROUND: Chronic abdominal pain in children may be caused by the anterior cutaneous nerve entrapment syndrome. Local nerve blocks are recommended as an initial treatment in adults. Evidence on effectiveness and safety of such a treatment in children is lacking. AIM: Our aim was to study outcome and adverse events of anterior rectus sheath blocks in childhood anterior cutaneous nerve entrapment syndrome. METHODS: Patients <18 years of age receiving anterior rectus sheath blocks were prospectively followed. Injections were administered using a free-hand technique in the outpatient department. RESULTS: A total of 85 children were included (median age 15 years, range 8-17, 76% female). Eighty-three children reported immediate pain relief following a single lidocaine block and 13 achieved long-term success. Another 19 children was successfully treated with additional blocks combined with steroids. A total 38% success ratio was attained after a median 17-month follow-up (range, 4-39). Pain intensity and diagnostic delay were not associated with a beneficial outcome. However, young age predicted success. An infrequently occurring adverse event was temporarily increased pain some 6 h post injection. CONCLUSION: Anterior rectus sheath blocks using local anesthetics and steroids are safe and long-term successful in more than one-third of children suffering from abdominal pain due to anterior cutaneous nerve entrapment syndrome.

Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation.

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.