Pascal Vanelderen

12. Pain Originating from the Lumbar Facet Joints

Although the existence of a “facet syndrome” had long been questioned, it is now generally accepted as a clinical entity. Depending on the diagnostic criteria, the zygapophysial joints account for between 5% and 15% of cases of chronic, axial low back pain. Most commonly, facetogenic pain is the result of repetitive stress and/or cumulative low‐level trauma, leading to inflammation and stretching of the joint capsule. The most frequent complaint is axial low back pain with referred pain perceived in the flank, hip, and thigh. No physical examination findings are pathognomonic for diagnosis. The strongest indicator for lumbar facet pain is pain reduction after anesthetic blocks of the rami mediales (medial branches) of the rami dorsales that innervate the facet joints. Because false‐positive and, possibly, false‐negative results may occur, results must be interpreted carefully. In patients with injection‐confirmed zygapophysial joint pain, procedural interventions can be undertaken in the context of a multidisciplinary, multimodal treatment regimen that includes pharmacotherapy, physical therapy and regular exercise, and, if indicated, psychotherapy. Currently, the “gold standard” for treating facetogenic pain is radiofrequency treatment (1 B+). The evidence supporting intra‐articular corticosteroids is limited; hence, this should be reserved for those individuals who do not respond to radiofrequency treatment (2 B±).

8. Occipital Neuralgia

Occipital neuralgia is defined as a paroxysmal shooting or stabbing pain in the dermatomes of the nervus occipitalis major and/or nervus occipitalis minor. The pain originates in the suboccipital region and radiates over the vertex. A suggestive history and clinical examination with short‐term pain relief after infiltration with local anesthetic confirm the diagnosis. No data are available about the prevalence or incidence of this condition. Most often, trauma or irritation of the nervi occipitales causes the neuralgia. Imaging studies are necessary to exclude underlying pathological conditions. Initial therapy consists of a single infiltration of the culprit nervi occipitales with local anesthetic and corticosteroids (2 C+). The reported effects of botulinum toxin A injections are contradictory (2 C±). Should injection of local anesthetic and corticosteroids fail to provide lasting relief, pulsed radio‐frequency treatment of the nervi occipitales can be considered (2 C+). There is no evidence to support pulsed radio‐frequency treatment of the ganglion spinale C2 (dorsal root ganglion). As such, this should only be done in a clinical trial setting. Subcutaneous occipital nerve stimulation can be considered if prior therapy with corticosteroid infiltration or pulsed radio‐frequency treatment failed or provided only short‐term relief (2 C+).

13. Sacroiliac joint pain

The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower limb(s). Because sacroiliac joint pain is difficult to distinguish from other forms of low back pain based on history, different provocative maneuvers have been advocated. Individually, they have weak predictive value, but combined batteries of tests can help ascertain a diagnosis. Radiological imaging is important to exclude “red flags” but contributes little in the diagnosis. Diagnostic blocks are the diagnostic gold standard but must be interpreted with caution, because false‐positive as well as false‐negative results occur frequently. Treatment of sacroiliac joint pain is best performed in the context of a multidisciplinary approach. Conservative treatments address the underlying causes (posture and gait disturbances) and consist of exercise therapy and manipulation. Intra‐articular sacroiliac joint infiltrations with local anesthetic and corticosteroids hold the highest evidence rating (1 B+). If the latter fail or produce only short‐term effects, cooled radiofrequency treatment of the lateral branches of S1 to S3 (S4) is recommended (2 B+) if available. When this procedure cannot be used, (pulsed) radiofrequency procedures targeted at L5 dorsal ramus and lateral branches of S1 to S3 may be considered (2 C+).

The role of brain-derived neurotrophic factor in different animal models of neuropathic pain

Even in present day pain therapy, neuropathic pain remains a challenge for clinicians to treat and a challenge for researchers to investigate. Different animal models have been developed to mimic neuropathic pain. Neurotrophins such as nerve growth factor, brain‐derived neurotrophic factor and neurotrophin 3 have been studied extensively in these models, yet few review articles concerning brain‐derived neurotrophic factor have been published. This article reassesses the literature concerning brain‐derived neurotrophic factor expression in the sciatic nerve chronic constriction injury model, the sciatic nerve transection model, the spinal nerve ligation model and the spinal nerve transection model and discusses differences in regulation of brain‐derived neurotrophic factor between these models and their causality with neuropathic pain.

Systemic Inflammation Decreases Pain Threshold in Humans In Vivo

Background Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. Methods and Results Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-α, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20±4 % and 13±3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7±3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. Conclusions and Significance In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.

Radiofrequency Treatment of Facet-related Pain: Evidence and Controversies

Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well-conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment.

Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator.

Background:Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was not studied in humans with regard to the treatment of neuropathic pain. Methods:In this randomized, double-blind, placebo-controlled clinical trial, patients with subacute lumbar radicular pain received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20 per group) for 14 days. Primary outcome measure was the pain intensity in the leg as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14. Secondary outcome measures were the reduction of neuropathic pain symptoms in the leg as determined with a neuropathic pain questionnaire, consumption of rescue medication, and adverse events on days 7 and 14. Results:Sixty patients were randomized and included in an intention-to-treat analysis. After 14 days, patients in the minocycline and amitriptyline groups reported a reduction of 1.47 (95% confidence interval, 0.16–2.83; P = 0.035) and 1.41 (95% confidence interval, 0.05–2.78; P = 0.043), respectively, in the numeric rating scale compared to the placebo group. No differences were seen in the neuropathic pain questionnaire values at any time point during treatment between the three groups. The rate of adverse events in the amitriptyline group was 10% versus none in the minocycline and placebo groups. No differences were noted in the consumption of rescue medication. Conclusions:Although both groups differed from placebo, their effect size was small and therefore not likely to be clinically meaningful.

Effects of chronic administration of amitriptyline, gabapentin and minocycline on spinal brain-derived neurotrophic factor expression and neuropathic pain behavior in a rat chronic constriction injury model

Background In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted. Methods In this placebo-controlled study, we investigated the effects of amitriptyline (5 mg/kg), gabapentin (50 mg/kg), and minocycline (25 mg/kg) twice a day on NP behavior in a sciatic chronic constriction injury (CCI) rat model. Drug treatment started 7 days after CCI and lasted 14 days. At postoperative day 21, spinal BDNF expression in laminae I and II was quantified using immunocytochemistry. Results Sciatic CCI resulted in NP behavior throughout the duration of the experiment in the placebo group. When administered for 2 weeks, minocycline (P ⩽ 0.001) and amitriptyline (P ⩽ 0.05), but not gabapentin, reduced thermal hyperalgesia. None of these drugs reduced mechanical allodynia. As opposed to amitriptyline and gabapentin, 2 weeks of treatment with minocycline reduced brain-derived, neurotrophic factor immunoreactivity (P ⩽ 0.05) in the ipsilateral dorsal horn. Conclusions Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP.

The Effect of Deep Versus Moderate Neuromuscular Block on Surgical Conditions and Postoperative Respiratory Function in Bariatric Laparoscopic Surgery: A Randomized, Double Blind Clinical Trial.

BACKGROUND: In recent literature, it has been suggested that deep neuromuscular block (NMB) improves surgical conditions during laparoscopy; however, the evidence supporting this statement is limited, and this was not investigated in laparoscopic bariatric surgery. Moreover, residual NMB could impair postoperative respiratory function. We tested the hypotheses that deep NMB could improve the quality of surgical conditions for laparoscopic bariatric surgery compared with moderate NMB and investigated whether deep NMB puts patients at risk for postoperative respiratory impairment compared with moderate NMB. METHODS: Sixty patients were evenly randomized over a deep NMB group (rocuronium bolus and infusion maintaining a posttetanic count of 1–2) and a moderate NMB group (rocuronium bolus and top-ups maintaining a train-of-four count of 1–2). Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome measures were the quality of surgical conditions assessed by a single surgeon using a 5-point rating scale (1 = extremely poor, 5 = optimal), the number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery. Secondary outcome measure was the postoperative pulmonary function assessed by peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity, and by the need for postoperative respiratory support. Data are presented as mean ± standard deviation with estimated treatment effect (ETE: mean difference [95% confidence interval]) for group comparisons. RESULTS: There was no statistically significant difference in the surgeon’s rating regarding the quality of the surgical field between the deep and moderate NMB group (4.2 ± 1.0 vs 3.9 ± 1.1; P = .16, respectively; ETE: 0.4 [−0.1, 0.9]). There was no difference in the proportional rating of surgical conditions over the 5-point rating scale between both groups (P = .91). The number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery were not statistically different between the deep and moderate NMB group (0.2 ± 0.9 vs 0.3 ± 1.0; P = .69; ETE: −0.1 [−0.5, 0.4] and 61.3 ± 15.1 minutes vs 70.6 ± 20.8 minutes; P = .07, ETE: −9.3 [−18.8, 0.1], respectively). All the pulmonary function tests were considerably impaired in both groups when compared with baseline (P < .001). There was no statistically significant difference in the decrease in peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity (expressed as % change from baseline) between the deep and the moderate NMB group. CONCLUSIONS: Compared with a moderate NMB, there was insufficient evidence to conclude that deep NMB improves surgical conditions during laparoscopic bariatric surgery. Postoperative pulmonary function was substantially decreased after laparoscopic bariatric surgery independently of the NMB regime that was used. The study is limited by a small sample size.

Diagnostic medial branch blocks before lumbar radiofrequency zygapophysial (facet) joint denervation: benefit or burden?

DEGENERATIVE changes of the zygapophysial joints (facet joints) account for approximately 10–15% of the cases with chronic low back pain. Radiofrequency ablation of the medial branches of the dorsal rami is a frequently performed procedure to treat pain originating from the facet joints. The success of radiofrequency facet denervation is highly dependent on patient selection. Diagnostic blocks are recommended in guidelines and reviews for selecting patients with facet joint pain from a population with nonspecific low back pain, however, with a large variation in the techniques of performing and assessing the blocks. Cohen et al. published in this issue of ANESTHESIOLOGY a randomized controlled trial (RCT) assessing three selection paradigms before radiofrequency lumbar facet denervation. The design and findings of this study provide an important contribution to the ongoing debate on patient selection and the so-called diagnostic blocks. The importance of the correctly performed and assessed diagnostic blocks becomes clear when examining the seven RCTs on radiofrequency lumbar facet denervation. In five of seven RCTs, the radiofrequency treatment has a superior outcome to its comparator, whereas there is one negative and one equivocal study. In all of these studies, diagnostic blocks were performed. However, there is no definitive standard on how to perform the diagnostic blocks, resulting in a wide variation of technique, medication used, dose, and whether to block the facet joint or its nerve supply as well as the interpretation of the results of such blocks, which is illustrated in table 1. Consequently, the percentage of patients who are ultimately selected for treatment varies from 10 to 92%, which is not in line with prevalence data of facet arthropathy (10–15%). These large variations in patient selection may contribute to the differences in observed success rates among different RCTs. The goal of diagnostic blocks is to select patients with facet joint pain, who are supposed to benefit mostly from the use of radiofrequency facet denervation. This can be expressed by the number of patients needed to be treated (NNT) to result in one patient with a positive outcome. The lower the NNT, the more effective the treatment. In the negative and equivocal RCT on radiofrequency facet denervation, patients were selected by means of aspecific intraarticular blocks instead of the medial branch blocks. Moreover, Leclaire et al. judged the intraarticular block with local anesthetic and corticosteroid to be positive when the patient reported “significant” pain relief during 24 h within the week after the injection. The 92% inclusion rate may reflect the high false-positive rate. The NNT in this study was 11.9 in the radiofrequency group. In a controlled study using single diagnostic medial branch blocks, where the outcome of the block was assessed by the patient with the help of a study nurse within 30 min after the injection, the prevalence of facet joint pain was 31%. The NNT in the radiofrequency group was 1.6. In a nonrandomized but high-quality prospective study, Dreyfuss et al. included patients after two positive controlled blocks with lidocaine and bupivacaine. The prevalence of facet joint pain was 10.8% and of NNT 1.1. In conclusion, the use of diagnostic intraarticular facet joint blocks cannot be recommended anymore, and better patient selection with medial branch diagnostic blocks improves the outcome of radiofrequency facet denervation. However, there are two concerns regarding a future standard recommendation for controlled diagnostic blocks. First, by increasing the number of diagnostic blocks, the falsepositive rate will be reduced, but unfortunately the falsenegative rate will increase, thus increasing the risk of withholding an active treatment from patients. Moreover, aberrant medial branch innervation was demonstrated in 11%, demonstrating an additional risk for false-negative blocks. The second concern is related to the balance of the burden of multiple interventions versus the potential benefit. The study by Cohen et al. published in this issue adds another piece of information to this complicated puzzle. The