Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.

Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.

Loss of Efficacy to Spinal Cord Stimulator Therapy: Clinical Evidence and Possible Causes.

BACKGROUND: Although spinal cord stimulation (SCS) therapy has been shown to be efficacious in various pain conditions, the ability for SCS therapy to maintain long-term efficacy has been questioned. OBJECTIVE: The purpose of this study was to investigate whether a loss of efficacy (LOE) phenomenon exists with SCS therapy and to investigate if this phenomenon is more apparent in any specific patient population. STUDY DESIGN: A retrospective, observation chart review was conducted to evaluate the patient response to SCS therapy over time. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Patients who received a SCS at the Massachusetts General Hospital, between January 1, 2002 and December 31, 2012, were invited to participate. A total of 62 patients were included in this study. Various models were created to analyze pain score changes over time using 2-tailed statistical analysis. Additionally, one-way ANOVA and Pearson's chi-square tests were used to determine if certain patient characteristics were associated with LOE. RESULTS: Compared to the visual analog scale (VAS) score at one month after device implantation, pain scores increased 1.95 points after 2 years (95% CI: 1.06 to 2.84, P = < 0.001). There were no significant differences in baseline characteristics between the groups of patients who did and did not lose efficacy of their therapy. However, those who experienced LOE had a baseline SCS therapy VAS score 3.09 points lower than those who did not (95% CI: 1.69 to 4.48, P = < 0.001). LIMITATIONS: This study had several limitations including the retrospective nature of its design, confounders to VAS scores, small sample size, missing data points, and the evaluation of only conventional, low-frequency SCS therapy. CONCLUSIONS: Patients who received a SCS had a significant increase in VAS scores over time. Our data did not show any baseline patient characteristic that helped predict LOE. However, patients who have significant baseline response to therapy may be more likely to experience LOE. KEY WORDS: Spinal cord stimulation, chronic pain, retrospective study, low frequency electrical stimulation, efficacy, chronic pain therapy.

High-Frequency Spinal Cord Stimulation for Chronic Pain: Pre-Clinical Overview and Systematic Review of Controlled Trials.

OBJECTIVE: To assess the evidence base for high-frequency spinal cord stimulation (HFSCS). HFSCS has the potential to provide paresthesia-free pain relief for patients with chronic pain, in contrast to conventional spinal cord stimulation, which produces distracting and potentially unpleasant paresthesias. DESIGN: A systematic review following standard methodological guidelines (Prospero #CRD42015029215). METHODS: We searched PubMed to March 14, 2016 without language restriction and hand-checked reference lists. Two authors independently performed study selection, bias evaluations, and data extraction. The pre-clinical review selected studies focusing on the mechanism and non-human experience with HFSCS. Clinically, any prospective study of adults using HFSCS (≥ 1000 Hz) was included. RESULTS: Pre-clinical studies have characterized many aspects underlying the mechanism of HFSCS. For the clinical systematic review, eight trials (236 participants randomized or 160 followed prospectively) met inclusion criteria. All trials of HFSCS focused on patients with chronic low back pain with one exception, which included patients with chronic migraine. All but one trial documented funding by industry. Performance bias due to unmasked participants, physicians, and outcome assessors limited the quality of all but one study. CONCLUSIONS: Significant growth in the preclinical and clinical evidence base for HFSCS suggests that HFSCS may differ from conventional SCS in mechanism of action and efficacy of treatment, respectively. Addressing current knowledge gaps in clinical evidence will require standardization in trial reporting and leveraging the paresthesia-free characteristic of HFSCS to enable masking in high-quality randomized controlled trials.

Effects of Spinal Cord Stimulation on Pain Thresholds and Sensory Perceptions in Chronic Pain Patients.

OBJECTIVE: Spinal cord stimulation (SCS) has been in clinical use for nearly four decades. In earliest observations, researchers found a significant increase in pain threshold during SCS therapy without changes associated with touch, position, and vibration sensation. Subsequent studies yielded diverse results regarding how SCS impacts pain and other sensory thresholds. This pilot study uses quantitative sensory testing (QST) to objectively quantify the impact of SCS on warm sensation, heat pain threshold, and heat pain tolerance. MATERIALS AND METHODS: Nineteen subjects with an indwelling SCS device for chronic pain were subjected to QST with heat stimuli. QST was performed on an area of pain covered with SCS-induced paresthesia and an area without pain and without paresthesia, while the SCS was turned off and on. The temperature at which the patient detected warm sensation, heat pain, and maximal tolerable heat pain was used to define the thresholds. RESULTS: We found that all three parameters, the detection of warm sensation, heat pain threshold, and heat pain tolerance, were increased during the period when SCS was on compared with when it was off. This increase was observed in both painful and non-painful sites. CONCLUSION: The observed pain relief during SCS therapy seems to be related to its impact on increased sensory threshold as detected in this study. The increased sensory threshold on areas without pain and without the presence of SCS coverage may indicate a central (spinal and/or supra-spinal) influence from SCS.

Effect of 1.5% Topical Diclofenac on Clinical Neuropathic Pain.

BACKGROUND: Neuropathic pain is a condition resulting from injury to the peripheral and/or central nervous system. Despite extensive research over the last several decades, neuropathic pain remains difficult to manage. METHODS: The authors conducted a randomized, placebo-controlled, double-blinded, and crossover clinical trial to examine the effect of 1.5% topical diclofenac (TD) on neuropathic pain. The authors hypothesized that 1.5% TD would reduce the visual pain score and improve both quantitative sensory testing and functional status in subjects with neuropathic pain. The authors recruited subjects with postherpetic neuralgia and complex regional pain syndrome. The primary outcome was subject's visual pain score. RESULTS: Twenty-eight subjects completed the study (12 male and 16 female) with the mean age of 48.8 yr. After 2 weeks of topical application, subjects in 1.5% TD group showed lower overall visual pain score compared with placebo group (4.9 [1.9] vs. 5.6 [2.1], difference: 0.8; 95% CI, 0.1 to 1.3; P = 0.04) as well as decreased burning pain (2.9 [2.6] vs. 4.3 [2.8], difference, 1.4; 95% CI, 0.2 to 2.6; P = 0.01). There were no statistical differences in constant pain, shooting pain, or hypersensitivity over the painful area between the groups. This self-reported improvement of pain was corroborated by the decreased pain summation detected by quantitative sensory testing. There were no statistically significant changes in functional status in these subjects. There were no complications in both groups. CONCLUSION: The findings indicate that 1.5% TD may serve as an effective treatment option for patients with neuropathic pain from postherpetic neuralgia and complex regional pain syndrome.

Diagnosis and treatment of posterior sacroiliac complex pain: a systematic review with comprehensive analysis of the published data.

OBJECTIVE: To assess the evidence on the validity of sacral lateral branch blocks and the effectiveness of sacral lateral branch thermal radiofrequency neurotomy in managing sacroiliac complex pain. DESIGN: Systematic review with comprehensive analysis of all published data. INTERVENTIONS: Six reviewers searched the literature on sacral lateral branch interventions. Each assessed the methodologies of studies found and the quality of the evidence presented. OUTCOME MEASURES: The outcomes assessed were diagnostic validity and effectiveness of treatment for sacroiliac complex pain. The evidence found was appraised in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of evaluating scientific evidence. RESULTS: The searches yielded two primary publications on sacral lateral branch blocks and 15 studies of the effectiveness of sacral lateral branch thermal radiofrequency neurotomy. One study showed multisite, multidepth sacral lateral branch blocks can anesthetize the posterior sacroiliac ligaments. Therapeutic studies show sacral lateral branch thermal radiofrequency neurotomy can relieve sacroiliac complex pain to some extent. The evidence of the validity of these blocks and the effectiveness of this treatment were rated as moderate in accordance with the GRADE system. CONCLUSIONS: The literature on sacral lateral branch interventions is sparse. One study demonstrates the face validity of multisite, multidepth sacral lateral branch blocks for diagnosis of posterior sacroiliac complex pain. Some evidence of moderate quality exists on therapeutic procedures, but it is insufficient to determine the indications and effectiveness of sacral lateral branch thermal radiofrequency neurotomy, and more research is required.

Epidural blood patch for postdural puncture positional vertigo.

STUDY DESIGN: Case report. OBJECTIVE: To report an unusual case of refractory positional vertigo without headache that developed after the placement of an epidural catheter for postoperative pain and that was treated with an epidural blood patch. SUMMARY OF THE BACKGROUND DATA: Although it is common practice to use epidural blood patch (EBP) to treat positional headache from postdural puncture (PDP), the literature is limited to one letter to the editor describing PDP positional vertigo treated with EBP. METHODS: Description of a clinical case. RESULTS: Here we present a case where the patient presented with the complaint of vertigo without headache and had a characteristic onset with upright position and marked relief when lying down. The patient received an EBP with complete resolution of her symptoms. CONCLUSIONS: This case illustrates patient can present with an isolated symptom such as dizziness without headache after PDP. The patient received an EBP with complete resolution of her symptom of postdural dizziness.

Epidural blood patch for chronic daily headache with postural component: a case report and the review of published cases.

Post dural puncture headache (PDPH) can be observed after any trauma to the dura. The hallmark of PDPH is an increasing headache when assuming the upright position and improvement with the supine position. Diagnosis of PDPH is essentially based on history of dural puncture and clinical presentation. In most cases, if initial conservative therapies fail to provide the relief of symptoms, an epidural blood patch is the therapy of choice. Epidural blood patch is a safe and effective treatment for PDPH and routinely done for acute onset of postural headache after spinal or epidural anesthesia or analgesia. Here, we report the successful treatment of chronic daily headache with a postural component via an epidural blood patch one year after the onset. We also review the literature pertinent to the use of epidural blood patch in chronic daily headache patients with postural component.

Peri-procedural protocols for interventional pain management techniques: a survey of US pain centers.

BACKGROUND: Interventional techniques are now an integral part of chronic pain management. As new procedures are arising at a rapid pace, decisions regarding patient safety and comfort are becoming more challenging. No peri-procedural consensus protocol currently addresses issues such as 1. nulla per os (NPO) status, 2. sedation, 3. monitoring, or 4. recovery. In establishing safety guidelines for interventional pain procedures, the knowledge of current peri-procedural protocols is required. OBJECTIVE: To survey interventional pain practices and to obtain current peri-procedural protocols. DESIGN: We faxed a one-page questionnaire to 105 United States pain practices identified using the directory of the American Pain Society. Fifty-seven academic and private pain practices (54%) responded and were included in the analysis. RESULTS: Monitoring devices such as electrocardiogram (EKG), blood pressure, and pulse oximetry are not universally employed for cervical or lumbar spinal procedures. Even procedures that are often performed by anesthesiologists in operating rooms, such as Bier blocks, are not monitored in a uniform manner when performed in pain clinics. Establishment of intravenous access for procedures also varies among practitioners. Most (72%) practices had treated patients with vasovagal reactions over the past 12 months, but only 42% had simulated cardiac arrests to prepare for these situations. CONCLUSION: While various trends in peri-procedural care are observable, standards of care are not well established. In order to minimize complications associated with interventional pain management techniques, the pain management community should agree on safety guidelines for all procedures, much as these advocated by the American Society of Anesthesiology for surgical anesthetic care.

Patient selection and trial methods for intraspinal drug delivery for chronic pain: a national survey.

Objectives Intraspinal drug delivery via indwelling pump is an effective means of treating refractory pain. Before a patient is selected for pump implantation, an intraspinal drug delivery trial must be performed to establish side-effects and efficacy profiles. No consensus protocol currently exists for such trials. As a preliminary step in this process, we surveyed a group of interventional pain physicians to explore attitudes on patient selection criteria, drug choice, trial techniques, and efficacy assessment. Methods The questionnaire was sent for self-administration to 1500 interventional pain physicians, each of whom had implanted one or more Medtronic(®) implantable infusion pumps. Results We received 205 completed surveys. Among the respondents, most were anesthesiologists (76%) and in private practice (82%). Nearly half (45%) of the respondents use the continuous intrathecal infusion technique to select patients for permanent implants. Conclusions Trial practices vary widely in terms of patient selection, medication choice, technique, and efficacy evaluation. We hope that our findings will encourage a concerted effort to evaluate existing trial protocols in order to establish a reliable standard of care.

Respiratory distress after intrathecal baclofen withdrawal.

We present the case of a 19-yr-old woman with a history of generalized dystonia who developed sudden onset of adductor spasms of the vocal cords and increased dystonia after the interruption or intrathecal baclofen therapy. Her symptoms resolved after intrathecal baclofen was restored. In patients with dystonia receiving intrathecal baclofen therapy, the onset of dyspnea associated with increased muscle tone should prompt the investigation of baclofen withdrawal.

Seizures after a Bier block with clonidine and lidocaine.

A 47-yr-old man with history of complex regional pain syndrome type 1 underwent an IV Bier block with a mixture of lidocaine and clonidine. The tourniquet was deflated after 60 min, and approximately 10 min later he presented with complex partial seizures. The possible mechanisms for this are discussed, and the effects of clonidine, lidocaine, and the mixture of both are reviewed, as are four additional published cases reporting seizures after the administration of clonidine.

The predictive value of sympathetic block for the success of spinal cord stimulation.

OBJECTIVE: The purpose of this study was to assess the predictive value of response to sympathetic blockade (SB) on the success rate of spinal cord stimulation (SCS) in patients with complex regional pain syndrome. METHODS: We performed a retrospective study on 23 patients with complex regional pain syndrome who underwent both SB and subsequent SCS trials in the past 3 years at the Massachusetts General Hospital Pain Center, Boston, MA, and Walter Reed Army Medical Center, Washington, DC. Fifteen of these patients underwent permanent placement of an SCS device, and pain relief at 1- and 9-month follow-up was recorded. RESULTS: Among the 23 patients included in the study, those having transient pain relief with SB were more likely to have a positive SCS trial: all 13 with positive SB had good pain relief during the trial, compared with only 3 of the 10 with negative SB (100% versus 30%, P < 0.001). Among the 10 patients with negative SB, 7 noted poor pain relief during the trial despite adequate coverage, and they did not undergo placement of a permanent device. Among the patients who underwent permanent placement of an SCS device, those who received good pain relief with SB were more likely to have greater than 50% pain relief at 1-month follow-up (100% versus 33%, P = 0.029) and 9-month follow-up (87.5% versus 33.3%, P = 0.15). CONCLUSION: We conclude that patients with good response to SB before SCS are more likely to have a positive response during their SCS trial and long-term pain relief after placement of permanent SCS device.

Complex regional pain syndrome type I after myocardial infarction treated with spinal cord stimulation.

OBJECTIVE: A rare case of Complex Regional Pain Syndrome (CRPS) type I after myocardial infarction (MI) and significant comorbid illness with few treatment options for pain control was successfully managed with the placement of a spinal cord stimulator (SCS). CASE REPORT: A 44-year-old man presented with left upper extremity burning pain after MI. His past medical history included insulin-dependent diabetes mellitus, oxygen-dependent idiopathic pulmonary fibrosis, and recent coronary revascularization surgery. His pain was presumed to be related to his MI and a clinical diagnosis of CRPS type I (or reflex sympathetic dystrophy) was made. Facing limited medical and less invasive options for his pain relief, he underwent a spinal cord stimulation trial with excellent response. He had more than 70% pain relief from the spinal cord stimulation at the last follow-up, 2 years later. CONCLUSION: CRPS type I after MI can be difficult to treat because of other comorbid illnesses. SCS can be a safe and effective mode of therapy for patients facing limited treatment options.