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Chronic low back pain (CLBP) is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine). Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories) to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs) for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres) retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1) blood collection, (2) sample processing and storage, (3) shipping details and (4) cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

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.

Background and Objectives: Radiofrequency ablation of genicular nerves has proved to be successful in relieving pain and incapacity caused by osteoarthritis of the knee. However, long-term efficacy of such a treatment remains to be assessed. The current study aimed to reproduce radiofrequency neurotomy of genicular nerves to manage gonarthrosis pain and disability and establish therapeutic response until 1 year after intervention., Methods: This single-center, prospective, observational, noncontrolled, longitudinal study included patients with grade 3 to 4 gonarthrosis suffering from intractable knee pain, scoring 5 or more on the visual analog scale (VAS) during >6 months. Therapy was based on ultrasound guided radiofrequency neurotomy of the superior medial, superior lateral and inferior medial genicular nerves. Visual analog scale and Western Ontario and McMaster Universities Osteoarthritis scores were assessed before therapy and at 1, 6, and 12 months following treatment., Results: Radiofrequency neurotomy of genicular nerves significantly reduced perceived pain (VAS) and disability (Western Ontario and McMaster Universities Osteoarthritis) in the majority of participants, without untoward events. The proportion of participants with improvement of 50% or greater in pretreatment VAS scores at 1, 6, and 12 months following intervention were 22/25 (88%), 16/25 (64%) and 8/25 (32%), respectively., Conclusions: Ultrasound-guided radiofrequency neurotomy of genicular nerves alleviates intractable pain and disability in the majority of patients with advanced osteoarthritis of the knee. Such a treatment is safe and minimally invasive and can be performed in an outpatient setting. The beneficial effect of treatment started to decline after 6 months, but even 1 year after the intervention, 32% of patients reported 50% improvement or greater in pretreatment VAS scores.

In recent decades, there has been a revision of the role of institutional review boards with the intention of protecting human subjects from harm and exploitation in research. Informed consent aims to protect the subject by explaining all of the benefits and risks associated with a specific research project. To date, there has not been a review published analyzing issues of informed consent in research in the field of genetic/Omics in subjects with chronic pain, and the current review aims to fill that gap in the ethical aspects of such investigation. Despite the extensive discussion on ethical challenges unique to the field of genetic/Omics, this is the first attempt at addressing ethical challenges regarding Informed Consent Forms for pain research as the primary focus. We see this contribution as an important one, for while ethical issues are too often ignored in pain research in general, the numerous arising ethical issues that are unique to pain genetic/Omics suggest that researchers in the field need to pay even greater attention to the rights of subjects/patients. This article presents the work of the Ethic Committee of the Pain-Omics Group (www.painomics.eu), a consortium of 11 centers that is running the Pain-Omics project funded by the European Community in the 7th Framework Program theme (HEALTH.2013.2.2.1-5-Understanding and controlling pain). The Ethic Committee is composed of 1 member of each group of the consortium as well as key opinion leaders in the field of ethics and pain more generally., (© 2016 The Authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.)

Introduction: Chronic low back pain (CLBP) produces considerable direct costs as well as indirect burdens for society, industry and health systems. CLBP is characterised by heterogeneity, inclusion of several pain syndromes, different underlying molecular pathologies and interaction with psychosocial factors that leads to a range of clinical manifestations. There is still much to understand in the underlying pathological processes and the non-psychosocial factors which account for differences in outcomes. Biomarkers that may be objectively used for diagnosis and personalised, targeted and cost-effective treatment are still lacking. Therefore, any data that may be obtained at the '-omics' level (glycomics, Activomics and genome-wide association studies-GWAS) may be helpful to use as dynamic biomarkers for elucidating CLBP pathogenesis and may ultimately provide prognostic information too. By means of a retrospective, observational, case-cohort, multicentre study, we aim to investigate new promising biomarkers potentially able to solve some of the issues related to CLBP., Methods and Analysis: The study follows a two-phase, 1:2 case-control model. A total of 12 000 individuals (4000 cases and 8000 controls) will be enrolled; clinical data will be registered, with particular attention to pain characteristics and outcomes of pain treatments. Blood samples will be collected to perform -omics studies. The primary objective is to recognise genetic variants associated with CLBP; secondary objectives are to study glycomics and Activomics profiles associated with CLBP., Ethics and Dissemination: The study is part of the PainOMICS project funded by European Community in the Seventh Framework Programme. The study has been approved from competent ethical bodies and copies of approvals were provided to the European Commission before starting the study. Results of the study will be reviewed by the Scientific Board and Ethical Committee of the PainOMICS Consortium. The scientific results will be disseminated through peer-reviewed journals., Trial Registration Number: NCT02037789; Pre-results., Competing Interests: Competing interests: The study is supported by a grant from the European Commission (602736). MA is a consultant for Grünenthal, Angelini and Mundipharma. He also collaborated for speeches with MSD and CareFusion. GL has multiple patents in the field of glycoscience issued. IKP is the research director of Photeomix, the commercial name of IP Research Consulting SAS, who have ongoing patent applications and trademarks related to Activomics. YSA is a director and co-owner of Maatschap PolyOmica, which provides (consulting) services in the area of (statistical) (gen)omics., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: In a previous prospective study on pulsed radiofrequency (PRF) treatment adjacent to the lumbar dorsal root ganglion (DRG) for patients with chronic lumbosacral radicular pain, we reported success in 55.4% of the patients at 6 months. Identification of predictors for success after PRF may improve outcome. We assessed the predictors of PRF in patients with chronic intractable lumbosacral radicular pain., Methods: Patients with monosegmental chronic lumbosacral radicular pain of L5 or S1 first received a selective nerve root block at the corresponding level. Independent of the result of this block a PRF treatment at the same level was performed. At 6 weeks, 3 months, and 6 months after the procedure the outcome was evaluated., Results: A positive diagnostic nerve root block and age ≥ 55 were predictive factors for successful outcome at 6 months, while disability was a negative predictor.The use of failed back surgery syndrome, gender, duration of pain, Numerical Rating Scale, level and side of treatment, DN4, and RAND-36 as predictors for success was not supported., Conclusions: Successful outcome after PRF adjacent to the DRG, in patients with intractable chronic lumbosacral radicular pain, is more likely in patients ≥ 55 years, with limited disability and after a positive diagnostic nerve root block. A combination of all these factors creates a fair predictive value (AUC: 0.73)., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Radiofrequency denervation of the cervical medial branches is a possible treatment for chronic cervical facet pain syndrome when conservative management has failed. According to the literature, complications after radiofrequency denervation of the cervical medial branches are rare. We report a case of possible phrenic nerve injury after ipsilateral radiofrequency denervation of the cervical medial branches following a posterolateral approach., (© 2015 World Institute of Pain.)

Background and Objectives: Systematic reviews evaluate the utility of procedural interventions of the spine, including epidural steroid injections (ESIs). However, existing quality assessment tools either fail to account for proper technical quality and patient selection or are not validated. We developed and validated a simple scale for ESIs to provide a quality assessment and rating of technique for injections of the spine (AQUARIUS)., Methods: Seven experts generated items iteratively based on prior ESI technique studies and professional judgment. Following testing for face and content validity, a 17-item instrument was used by 8 raters from 2 different backgrounds to assess 12 randomized controlled trials, selected from 3 different categories. Using frequency of assessment, a 12-item instrument was also generated. Both instruments underwent reliability (intraclass correlation coefficient), validity (ability to distinguish "low," "random," and "high" study categories), and diagnostic accuracy (receiver operating characteristics) testing., Results: Both 17- and 12-item instruments were scored consistently by raters regardless of background, with overall intraclass correlation coefficients of 0.72 (95% confidence interval [CI], 0.53-0.89) and 0.71 (95% CI, 0.51-0.89), respectively. Both instruments discriminated between clinical trials from all 3 categories. Diagnostic accuracy was similar for the 2 instruments, with areas under receiver operating characteristic curves of 0.89 (95% CI, 0.82-0.96) and 0.90 (95% CI, 0.82-0.97), respectively., Conclusions: The instrument in both 17- and 12-item formats demonstrates good reliability and diagnostic accuracy in rating ESI studies. As a complement to other tools that assess bias, the instrument may improve the ability to evaluate evidence for systematic reviews and improve clinical trial design.

Background and Objectives: There is little evidence concerning the medical management of lumbosacral radicular pain. The prognosis for patients suffering pain for more than 3 months is poor. Pulsed radiofrequency (PRF) treatment of the dorsal root ganglion (DRG) has been suggested as a minimally invasive treatment. We studied the effect on pain and quality of life of PRF treatment of the DRG in patients with chronic, severe lumbosacral radicular pain., Methods: Patients with lumbosacral radicular pain were screened to select a homogeneous population. PRF treatment of the DRG was performed at L5 or S1. Evaluation was carried out at 6 weeks, 3 months, and 6 months. Pain reduction and "fully recovered" or "much improvement," in terms of the global perceived effect, were the primary outcomes. Quality of life (RAND-36), disability (Oswestry Disability Index), and the neuropathic pain scales leeds assessment of neuropathic symptoms and signs (LANSS) and DN4 were registered at each time point. Medication use was scored with the Medication Quantification Scale., Results: Out of 461 screened patients, 65 were included. According to the intention to treat analysis, clinical success was achieved in 56.9%, 52.3%, and 55.4% of the patients at respectively 6 weeks, 3 months, and 6 months. DN4, Oswestry Disability Index and physical component for the RAND-36 quality of life improved significantly while the mental component remained unchanged. The number of patients on opioids was reduced., Conclusions: PRF treatment of the DRG may be considered for patients with chronic, severe lumbosacral radicular pain refractory to conventional medical management., (Wiley Periodicals, Inc.)

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.

It is often said that regional anesthesia is the practice of applied anatomy. Therefore, it is fitting that on the occasion of his 500th birthday, we celebrate the life and work of the brilliant Flemish anatomist, Andreas Vesalius (1514-1564), the founder of modern anatomy.

Cervical radicular pain presents itself as pain radiating from the neck to the arm. If conservative treatment fails, a cervical epidural steroid injection can be considered. A rare but possible complication resulting from the interlaminar approach is unintentional cervical dural puncture that may result in post-dural puncture headache (PDPH). Dural puncture from an interlaminar cervical epidural injection reportedly range from 0.25% to 2.65%. An epidural blood patch is a possible treatment option when conservative treatment fails. Relief could be secondary to 'sealing' of the dural tear from the clotted blood and reestablishment of physiological intracranial pressure. Another theory is an increase in the subarachnoid pressure from the injected blood. The increased pressure may restore normal intracranial pressure. We describe 2 cases of cervical PDPH treated with lumbar epidural blood patch. In 1 case, there was complete resolution of the symptoms and in the other case, there was great improvement of symptoms and a high thoracic blood patch was performed to resolve the remaining headache., (© 2014 World Institute of Pain.)

Chronic pain may recur after initial response to strong opioids in both patients with cancer and patients without cancer or therapy may be complicated by intolerable side effects. When minimally invasive interventional pain management techniques also fail to provide satisfactory pain relief, continuous intrathecal analgesic administration may be considered. Only 3 products have been officially approved for long-term intrathecal administration: morphine, baclofen, and ziconotide. The efficacy of intrathecal ziconotide for the management of patients with severe chronic refractory noncancer pain was illustrated in 3 placebo-controlled trials. A randomized study showed this treatment option to be effective over a short follow-up period for patients with pain due to cancer or AIDS. The efficacy of intrathecal opioid administration for the management of chronic noncancer pain is mainly derived from prospective and retrospective noncontrolled trials. The effect of intrathecal morphine administration in patients with pain due to cancer was compared with oral or transdermal treatment in a randomized controlled trial, which found better pain control and fewer side effects with intrathecal opioids. Other evidence is derived from cohort studies. Side effects of chronic intrathecal therapy may either be technical (catheter or pump malfunction) or biological (infection). The most troublesome complication is, however, the possibility of granuloma formation at the catheter tip that may induce neurological damage. Given limited studies, the evidence for intrathecal drug administration in patients suffering from cancer-related pain is more compelling than that of chronic noncancer pain., (© 2013 World Institute of Pain.)

Lumbosacral radicular pain is a pain in the distribution area of one of the nerves of the lumbosacral plexus, with or without sensory and/or motor impairment. A major source of lumbosacral radicular pain is failed back surgery, which is defined as persistent or recurrent pain, mainly in the region of the lower back and legs even after technically, anatomically successful spine surgeries. If lumbosacral radicular neuropathic pain fails to respond to conservative or interventional treatments, epiduroscopy can be performed as part of a multidisciplinary approach. Epiduroscopy aids in identifying painful structures in the epidural space, establishing a diagnosis and administering therapy. The novelty consists in the use of an epiduroscope to deliver therapies such as adhesiolysis and targeted administration of epidural medications. Clinical trials report favorable treatment outcomes in 30% to 50% of patients. Complications are rare and related to the rate or volume of epidural fluid infusion or inadvertent dural puncture. In patients with lumbosacral radicular pain, especially after back surgery, epiduroscopy with adhesiolysis may be considered (evidence rating 2 B+)., (© 2013 World Institute of Pain.)

Radicular pain is an important health care problem, with only limited evidence-based treatments available. Treatment selection should ideally target documented pathophysiological pathways. In herniated discs, a sequence in the inflammatory cascade can be observed that initiates and maintains increased nociceptive signal input. Inflammatory mediators including tumor necrosis factor α are released from the nucleus pulposus and the degenerating peripheral nerve, which, in turn, induces production of neurotrophins like nerve growth factor and brain-derived neurotrophic factor. Neurotrophins interfere not only with the generation of ectopic firing of nociceptive neurons in the dorsal root ganglion but also with the excitability and sensitization of neuronal transmission in the dorsal spinal horn. Radicular pain is further characterized by the electrophysiological spreading of the afferent nociceptive input over different spinal nerve roots. Both the complex pathophysiological pathways involved and the spreading of the nociceptive signal make radicular pain difficult to treat. Pulsed radiofrequency (PRF) is considered an option in treatment of radicular pain. To understand and increase the efficiency of PRF interventional treatments in radicular pain, both in vitro and in vivo studies aiming at elucidating part of the mechanism of action of PRF are described. Potential factors that may improve the efficacy of PRF treatment in radicular pain are discussed.

Background: Anatomical validation studies of cervical ultrasound images are sparse. Validation is crucial to ensure accurate interpretation of cervical ultrasound images and to develop standardized reliable ultrasound procedures to identify cervical anatomical structures. The aim of this study was to acquire validated ultrasound images of cervical bony structures and to develop a reliable method to detect and count the cervical segmental levels., Methods: An anatomical model of a cervical spine, embedded in gelatin, was inserted in a specially developed measurement device. This provided ultrasound images of cervical bony structures. Anatomical validation was achieved by laser light beams projecting the center of the ultrasound image on the cervical bony structures through a transparent gelatin., Results: Anatomically validated ultrasound images of different cervical bony structures were taken from dorsal, ventral, and lateral perspectives. Potentially relevant anatomical landmarks were defined and validated. Test/retest analysis for positioning showed a reproducibility with an intraclass correlation coefficient for single measures of 0.99. Besides providing validated ultrasound images of bony structures, this model helped to develop a method to detect and count the cervical segmental levels in vivo at long-axis position, in a dorsolateral (paramedian) view at the level of the laminae, starting from the base of the skull and sliding the ultrasound probe caudally., Conclusions: Ultrasound bony images of the cervical vertebrae were validated with an in vitro model. Anatomical bony landmarks are the mastoid process, the transverse process of C1, the tubercles of C6 and C7, and the cervical laminae. Especially, the cervical dorsal laminae serve best as anatomical bony landmarks to reliably detect the cervical segmental levels in vivo.

Background: Over 50% of patients presenting to pain clinic with neck pain have the cervical facet joints as the source of pain. Radiofrequency (RF) treatment of the medial branch, innervating the facet joint, is a therapeutic option. The objectives of this study were to evaluate the therapeutic effect and its duration of RF treatment, using the single posterior-lateral approach in patients suffering from facet joint degeneration and to identify predictors for a long-term effect., Methods: Of the 130 consecutive patients with axial neck pain referred to the University Pain Center Maastricht, 67 fulfilled the inclusion criteria. The therapeutic effect was measured using the Patients' Global Impression of Change (PGIC) scale. Retrospective data were made complete using newly collected PGIC follow-up data. A Kaplan-Meier curve evaluated the long-term therapeutic effect. Possible predictors of outcome were evaluated., Results: Two patients refused to participate and in the remaining 65 patients, overall pain relief was reported in 55.4% at 2-month follow-up. Moderately, important change of improvement and substantial change of improvement were seen in 50.8% of patients. At 3-year follow-up, 30% still reported pain reduction. Spinal treatment level was the only predictor found., Conclusions: Radiofrequency treatment of the cervical facet joints using a single posterior-lateral approach is a promising technique in patients with chronic neck pain due to facet degeneration. The short-term and long-term therapeutic effects of this intervention justify a randomized controlled trial to estimate the efficacy of cervical facet joint RF treatment in a chronic neck pain population., (© 2013 The Authors Pain Practice © 2013 World Institute of Pain.)

Background: Pain is a major problem for chronic pancreatitis (CP) patients. Unfortunately, medical therapy often fails. Endoscopic and surgical treatments are invasive, and results vary. Percutaneous radiofrequency ablation of the splanchnic nerves (RFSN) is a relatively new and minimally invasive procedure for treatment of intractable pain in CP patients., Materials and Methods: We retrospectively evaluated 18 RFSN procedures in 11 CP patients, all refractory to analgesics. Five patients underwent a second procedure; two patients underwent a third procedure. NRS pain scores were assessed. Complications, analgesics usage, and length of the pain-free period were recorded., Results: Radiofrequency ablation of the splanchnic nerves was effective in 15/18 interventions. The mean NRS pain score decreased from 7.7 ± 1.0 to 2.8 ± 2.7 (P ≤ 0.001). The pain-free period lasted for a median period of 45 weeks. The effect of repeated interventions was comparable to the initial procedure. One transient side effect was reported. Four patients reported significantly reduced analgesic usage; 4 patients completely stopped their pain medication., Conclusion: Radiofrequency ablation of the splanchnic nerves is a minimally invasive, effective procedure for pain relief. After the effect has subsided, RFSN can be successfully repeated. RFSN might become an alternative treatment in a selected group of CP patients. A larger, randomized trial is justified to substantiate these findings., (© 2013 The Authors Pain Practice © 2012 World Institute of Pain.)

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.

Background: The PainDETECT-Questionnaire (PDQ) helps to identify neuropathic components in patients suffering from pain. It can be used by clinicians in daily practice and in clinical trials., Aim: The aim of this study is to perform a translation and cross-cultural adaptation of the PDQ for use in the Netherlands and Belgium., Methods: The first phase was to translate and cross-culturally adapt the PDQ to Dutch. The second phase was to assess the face validity in the Netherlands and Belgium using qualitative and quantitative data collection., Results: The length, the readability, and the clarity of the questionnaire were good for all patients. The questionnaire was judged to have a good layout and to be clearly organized., Conclusion: The PDQ Dutch language Version is a well translated and cross-culturally adapted questionnaire, which might be useful for screening for neuropathic components of pain in the Netherlands and Belgium., (© 2012 Kris. C. P. Vissers. Pain Practice © 2012 World Institute of Pain.)

SUMMARY Low back pain is one of the most prominent healthcare problems but there is no gold standard for its diagnosis. Aspecific low back pain can be subdivided into radicular and mechanical pain. The diagnosis mainly relies on a combination of elements, such as medical history, physical examination, medical imaging and other possible additional tests. Once a working diagnosis has been established, confirmation of the causative structure and level is sought by means of diagnostic blocks. The use of the different diagnostic tests and blocks should be guided by the balance between the potential benefit (mainly in terms of improved treatment outcome, the possible burden for the patient and the chances of withholding potential effective treatment to patients) with false-negative test results.

Introduction: Complex regional pain syndrome type 1 (CRPS-1) has a 31% probability of becoming chronic. The early use of spinal cord stimulation (SCS) has been recommended as a strategy to prevent chronicity and functional impairment., Methods: In a prospective study, we treated 74 CRPS-1 patients with a mean disease duration of 17 weeks with standard therapy consisting of physical therapy, topical dimethyl sulfoxide, analgesics, transcutaneous stimulation, and sympathetic blockade. Patients who did not respond to standard therapy were offered a treatment with SCS. In these patients, we investigated the impact on pain, quality of life, and function., Results: Out of these 74 patients treated with standard therapy, six patients were included for early SCS treatment. The overall mean pain relief after one year was 35%. The mental component of the Short Form 36 improved; however, there was no effect on the physical component. None of the SCS treated patients showed a clear improvement in functional outcome., Discussion: We conclude that the feasibility of performing a randomized controlled trial on early SCS therapy in CRPS-1 is low because of the good disease improvement with standard therapy in the first year after onset. This study raises questions about the need to use SCS early in the course of CRPS-1 because of the probable lack of additional benefit compared with SCS in chronic CRPS-1., (© 2012 International Neuromodulation Society.)

Most studies on comorbidity in low back pain (LBP) have been conducted in specialized settings with the use of self-reports. This study has an original design using data from family practices: the incidence of the most frequent diseases was compared in patients with and without LBP in 2004. The database includes data from 67 family physicians in 52 family practices in Flanders, Belgium. It contains data from 160,000 different patients with 1,500,000 diagnoses during the period 1994 to 2004. The incidence of the most frequent diagnoses is presented in patients with and without LBP in 2004. The diagnoses were coded according to the ICPC-2-classification. In 2004, the incidence of LBP was 51.4‰ (95% CI: 49.8 to 53.1) in patients aged 18 or older. The incidence was slightly higher in women than in men: 53.0‰ (95% CI: 50.7 to 55.4) vs. 49.9‰ (95% CI: 47.7 to 52.3). The highest incidence was recorded in the age group of 50 to 54 years. The most frequent "other" diagnoses in patients with and without LBP are comparable, but some were more frequent in patients with LBP. Respiratory infections and diseases of the locomotor apparatus (neck syndrome, bursitis) are more frequent in patients with LBP. Low back pain is one of the most frequent diagnoses in general practice. Striking is the relatively higher frequency of common self-limiting diseases in patients with a diagnosis of LBP during the same year. To the authors' knowledge, this is the first time that medical demands for non-LBP reasons in family practice have been reported in patients with LBP., (© 2011 The Authors. Pain Practice © 2011 World Institute of Pain.)

Chronic pancreatitis is defined as a progressive inflammatory response of the pancreas that has lead to irreversible morphological changes of the parenchyma (fibrosis, loss of acini and islets of Langerhans, and formation of pancreatic stones) as well as of the pancreatic duct (stenosis and pancreatic stones). Pain is one of the most important symptoms of chronic pancreatitis. The pathogenesis of this pain can only partly be explained and it is therefore often difficult to treat this symptom. The management of pain induced by chronic pancreatitis starts with lifestyle changes and analgesics. For the pharmacological management, the three-step ladder of the World Health Organization extended with the use of co-analgesics is followed. Interventional pain management may consist of radiofrequency treatment of the nervi splanchnici, spinal cord stimulation, endoscopic stenting or stone extraction possibly in combination with lithotripsy, and surgery. To date, there are no randomized controlled trials supporting the efficacy of radiofrequency and spinal cord stimulation. The large published series reports justify a recommendation to consider these treatment options. Radiofrequency treatment, being less invasive than spinal cord stimulation, could be tested prior to considering spinal cord stimulation. There are several other treatment possibilities such as endoscopic or surgical treatment, pancreatic enzyme supplementation and administration of octreotide and antioxidants. All may have a role in the management of pain induced by chronic pancreatitis., (© 2011 The Authors. Pain Practice © 2011 World Institute of Pain.)

Introduction: Lumbosacral radicular syndrome (LRS) is probably the most frequent neuropathic pain syndrome. Three months to 1 year after onset, 30% of the patients still experience ongoing pain. The management of those patients is complex, and treatment success rates are rather low. The beneficial effect of pulsed radiofrequency (PRF) therapy has been described for the treatment of LRS in case reports and in retrospective and prospective studies. Up until now, no neurological complications have been reported after PRF treatment. The current clinical audit has been performed to assess the amount of pain relief after a single PRF treatment., Methods: Sixty consecutive patients who received a PRF treatment adjacent to the lumbar dorsal root ganglion for the management of LRS in the period 2007-2009 were included. The main study objective was to measure the reduction of pain after the pulsed radiofrequency treatment by using the global perceived effect. The primary end point was defined as at least 50% pain relief for a period of 2 months or longer., Results: The primary end point was achieved in 29.5% of all the PRF interventions. After 6 months, 50% pain relief was still present in 22.9% of the cases and after 12 months in 13.1% of the cases. The need for pain medication was significantly lower after pulsed radiofrequency treatment in the success group compared with the nonsuccess group., Conclusions: PRF treatment can be considered for the management of LRS patients. These results need to be confirmed in a randomized clinical trial., (Wiley Periodicals, Inc.)

Meralgia paresthetica (MP) is a neurological disorder of the nervus cutaneous femoris lateralis (lateral femoral cutaneous nerve) (LFCN) characterized by a localized area of paresthesia and numbness on the anterolateral aspect of the thigh. Medical history and neurological examination are essential in making the diagnosis. However, red flags such as tumor and lumbar disc herniations must be ruled out. While the diagnosis of MP is essentially a clinical diagnosis, sensory nerve conduction velocity studies are a useful additional diagnostic tool.The first choice in management of MP is, besides treating the underlying cause, always a conservative approach. Simple measures such as losing weight and not wearing tight belts and ⁄ or trousers can be advised. Pharmacological therapy consists mainly of antineuropathic medication.Anatomical variants of the LFCN occur in a quarter of patients and may be the reason for negative response to diagnostic blocks. For interventional treatment of MP, such as local injection with anesthetics and corticosteroids or pulsed radiofrequency treatment of the LFCN, the evidence is limited. In particular, pulsed radiofrequency treatment of the LFCN should only take place in a study context.

In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM-induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second-line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related., (© 2010 The Authors. Pain Practice © 2010 World Institute of Pain.)

Coccygodynia is painful condition localized in the region of the coccyx. In most cases a traumatic etiology is present. In the idiopathic form other causes such as infections and tumor have to be excluded. Coccygodynia can also be the result of pain referred from visceral structures due to conditions such as disorders of the rectum, the colon sigmoideum, and the urogenital system. In case of a traumatic etiology the diagnosis is made based on the typical medical history whereby the pain is provoked by prolonged sitting and cycling. Lateral images of the coccyx are always indicated. The same is true for manual examination of the coccyx. In case of absence of provocation of the coccygeal pain by prolonged sitting and manual examination neurological causes such as lumbar disc hernias are a possible reason for the coccygodynia. In the acute phase the first choice of treatment are NSAIDs. Treatment for patients with severe pain in the chronic phase consists of manual therapy and/or a local injection of local anesthetic and corticosteroid into the painful segment (2 C+). Other interventional treatments such as intradiscal injections, ganglion impar block, radiofrequency treatment and caudal block are advised only under study conditions (0). Coccygectomy is not recommended because of long-term moderate results and the chance of major complications., (© 2010 The Authors. Pain Practice © 2010 World Institute of Pain.)

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±)., (© 2010 World Institute of 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+)., (© 2010 World Institute of Pain.)

Painful shoulder complaints have a high incidence and prevalence. The etiology is not always clear. Clinical history and the active and passive motion examination of the shoulder are the cornerstones of the diagnostic process. Three shoulder tests are important for the examination of shoulder complaints: shoulder abduction, shoulder external rotation, and horizontal shoulder adduction. These tests can guide the examiner to the correct diagnosis. Based on this diagnosis, in most cases, primarily a conservative treatment with nonsteroidal anti-inflammatory drugs possibly in combination with manual and/or exercise therapy can be started. When conservative treatment fails, injection with local anesthetics and corticosteroids can be considered. In the case of frozen shoulder, a continuous cervical epidural infusion of local anesthetic and small doses of opioids or a pulsed radiofrequency treatment of the nervus suprascapularis can be considered.

Lumbosacral radicular pain is characterized by a radiating pain in one or more lumbar or sacral dermatomes; it may or may not be accompanied by other radicular irritation symptoms and/or symptoms of decreased function. The annual prevalence in the general population, described as low back pain with leg pain traveling below the knee, varied from 9.9% to 25%, which means that it is presumably the most commonly occurring form of neuropathic pain. The patient's history may give a suggestion of lumbosacral radicular pain. The best known clinical investigation is the straight-leg raising test. Final diagnosis is made based on a combination of clinical examination and potentially additional tests. Medical imaging studies are indicated to exclude possible serious pathologies and to confirm the affected level in patients suffering lumbosacral radicular pain for longer than 3 months. Magnetic resonance imaging is preferred. Selective diagnostic blocks help confirming the affected level. There is controversy concerning the effectiveness of conservative management (physical therapy, exercise) and pharmacological treatment. When conservative treatment fails, in subacute lumbosacral radicular pain under the level L3 as the result of a contained herniation, transforaminal corticosteroid administration is recommended (2 B+). In chronic lumbosacral radicular pain, (pulsed) radiofrequency treatment adjacent to the spinal ganglion (DRG) can be considered (2 C+). For refractory lumbosacral radicular pain, adhesiolysis and epiduroscopy can be considered (2 B+/-), preferentially study-related. In patients with a therapy-resistant radicular pain in the context of a Failed Back Surgery Syndrome, spinal cord stimulation is recommended (2 A+). This treatment should be performed in specialized centers.

Background: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis., Methods: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care., Results: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options., Conclusion: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial.

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., (Copyright 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Cervicogenic headache is mainly characterized by unilateral headache symptoms which arise from the neck radiating to the fronto-temporal and possibly to the supra-orbital region. Physical examination to find evidence of a disorder known to be a valid cause of headache encompasses movement tests of the cervical spinal column and segmental palpation of the cervical facet joints and soft tissues of the neck. Injection of the nervus occipitalis major is recommended after unsatisfactory results with conservative treatments (1 B+). In the case of an unsatisfactory outcome after injection of the nervus occipitalis major, radiofrequency treatment of the ramus medialis (medial branch) of the cervical ramus dorsalis can be considered (2 B+/-). If the result is unsatisfactory pulsed radiofrequency treatment of the ganglion spinale (dorsal root ganglion) of C2 and/or C3 can be considered in a study context (O).

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+).

Whiplash-associated disorders are comprised of a range of symptoms of which neck complaints and headaches are the most significant spine related. In the acute and sub-acute stage of the disorder, conservative treatment for minimally 6 months is recommended, active mobilization is slightly better than passive treatment. Thereafter, interventional treatment may be considered. The available evidence for injection of Botulinum toxin A (2 B-) and intra-articular corticosteroid injections (2 C-) supports a negative recommendation. Radiofrequency treatment of the ramus medialis (medial branch) of the ramus dorsalis is recommended (2 B+).

Background and Objectives: Occipital neuralgia is a paroxysmal nonthrobbing, stabbing pain in the area of the greater or lesser occipital nerve caused by irritation of these nerves. Although several therapies have been reported, no criterion standard has emerged. This study reports on the results of a prospective trial with 6 months of follow-up in which pulsed radiofrequency treatment of the greater and/or lesser occipital nerve was used to treat this neuralgia., Methods: Patients presenting with clinical findings suggestive of occipital neuralgia and a positive test block of the occipital nerves with 2 mL of local anesthetic underwent a pulsed radiofrequency procedure of the culprit nerves. Mean scores for pain, quality of life, and medication intake were measured 1, 2, and 6 months after the procedure. Pain was measured by the visual analog and Likert scales, quality of life was measured by a modified brief pain questionnaire, and medication intake was measured by a Medication Quantification Scale., Results: During a 29-month period, 19 patients were included in the study. Mean visual analog scale and median Medication Quantification Scale scores declined by 3.6 units (P = 0.002) and 8 units (P = 0.006), respectively, during 6 months. Approximately 52.6% of patients reported a score of 6 (pain improved substantially) or higher on the Likert scale after 6 months. No complications were reported., Conclusions: Pulsed radiofrequency treatment of the greater and/or lesser occipital nerve is a promising treatment of occipital neuralgia. This study warrants further placebo-controlled trials.

More than 50% of patients presenting to a pain clinic with neck pain may suffer from facet-related pain. The most common symptom is unilateral pain without radiation to the arm. Rotation and retroflexion are frequently painful or limited. The history should exclude risk factors for serious underlying pathology (red flags). Radiculopathy may be excluded with neurologic testing. Direct correlation between degenerative changes observed with plain radiography, computerized tomography, and magnetic resonance imaging and pain has not been proven. Conservative treatment options for cervical facet pain such as physiotherapy, manipulation, and mobilization, although supported by little evidence, are frequently applied before considering interventional treatments. Interventional pain management techniques, including intra-articular steroid injections, medial branch blocks, and radiofrequency treatment, may be considered (0). At present, there is no evidence to support cervical intra-articular corticosteroid injection. When applied, this should be done in the context of a study. Therapeutic repetitive medial branch blocks, with or without corticosteroid added to the local anesthetic, result in a comparable short-term pain relief (2 B+). Radiofrequency treatment of the ramus medialis of the cervical ramus dorsalis (facet) may be considered. The evidence to support its use in the management of degenerative cervical facet joint pain is derived from observational studies (2 C+).

Cervical radicular pain is defined as pain perceived as arising in the arm caused by irritation of a cervical spinal nerve or its roots. Approximately 1 person in 1,000 suffers from cervical radicular pain. In the absence of a gold standard, the diagnosis is based on a combination of history, clinical examination, and (potentially) complementary examination. Medical imaging may show abnormalities, but those findings may not correlate with the patient's pain. Electrophysiologic testing may be requested when nerve damage is suspected but will not provide quantitative/qualitative information about the pain. The presumed causative level may be confirmed by means of selective diagnostic blocks. Conservative treatment typically consists of medication and physical therapy. There are no studies assessing the effectiveness of different types of medication specifically in patients suffering cervical radicular pain. Cochrane reviews did not find sufficient proof of efficacy for either education or cervical traction. When conservative treatment fails, interventional treatment may be considered. For subacute cervical radicular pain, the available evidence on efficacy and safety supports a recommendation (2B+) of interlaminar cervical epidural corticosteroid administration. A recent negative randomized controlled trial of transforaminal cervical epidural corticosteroid administration, coupled with an increasing number of reports of serious adverse events, warrants a negative recommendation (2B-). Pulsed radiofrequency treatment adjacent to the cervical dorsal root ganglion is a recommended treatment for chronic cervical radicular pain (1B+). When its effect is insufficient or of short duration, conventional radiofrequency treatment is recommended (2B+). In selected patients with cervical radicular pain, refractory to other treatment options, spinal cord stimulation may be considered. This treatment should be performed in specialized centers, preferentially study related.

Cluster headache is a strictly unilateral headache that is associated with ipsilateral cranial autonomic symptoms and usually has a circadian and circannual pattern. Prevalence is estimated at 0.5 to 1.0/1,000. The diagnosis of cluster headache is made based on the patient's case history. There are two main clinical patterns of cluster headache: the episodic and the chronic. Episodic is the most common pattern of cluster headache. It occurs in periods lasting 7 days to 1 year and is separated by at least a 1-month pain-free interval. The attacks in the chronic form occur for more than 1 year without remission periods or with remission periods lasting less than 1 month. Conservative therapy consists of abortive and preventative remedies. Ergotamines and sumatriptan injections, sublingual ergotamine tartrate administration, and oxygen inhalation are effective abortive therapies. Verapamil is an effective and the safest prophylactic remedy. When pharmacological and oxygen therapies fail, interventional pain treatment may be considered. The effectiveness of radiofrequency treatment of the ganglion pterygopalatinum and of occipital nerve stimulation is only evaluated in observational studies, resulting in a 2 C+ recommendation. In conclusion, the primary treatment is medication. Radiofrequency treatment of the ganglion pterygopalatinum should be considered in patients who are resistant to conservative pain therapy. In patients with cluster headache refractory to all other treatments, occipital nerve stimulation may be considered, preferably within the context of a clinical study.