Opioid-sparing effect of intravenous outpatient ketamine infusions appears short-lived in chronic-pain patients with high opioid requirements.

BACKGROUND AND OBJECTIVES: Ketamine is opioid-sparing. It attenuates the onset of opioid tolerance, and suppresses opioid-induced hyperalgesia. This study evaluated whether or not repeated outpatient infusions of intravenous ketamine reduced the amount of pain and the amount of opioid requirements for patients suffering with chronic, non-cancerous pain. STUDY DESIGN: Retrospective study SETTING: Outpatient pain clinic METHODS: We reviewed the records of 18 patients taking high doses of opioids chronically and nonetheless reporting poorly controlled pain. A comparison control group of 18 similar patients with high opioid requirements who were not given ketamine were selected from our clinic population. INTERVENTION: Intravenous ketamine infusions MEASUREMENT: VAS pain scores and opioid use RESULTS: Morphometric and demographic characteristics, baseline opioid use, and pain scores were similar in the ketamine and comparison groups. Five patients given ketamine experienced no benefit and discontinued treatment after 1-2 infusions. One patient developed a supraventricular arrhythmia which immediately resolved upon cessation of the infusion. And another, despite pain relief, felt overly-anxious and opted out. Eleven patients thus completed 3-6 weekly ketamine infusions. At 6 months, 5 patients maintained less than 50% of their baseline opioid use, while the remaining patients returned to the baseline opioid use or increased their requirements. There was no significant difference in pain scores at 6 months in patients who received ketamine infusions and control group patients. LIMITATIONS: Retrospective nature of the study CONCLUSIONS: Outpatient intravenous ketamine infusions did not improve long-term pain scores in patients with high opioid requirements and only a few were able to substantially reduce opioid use. Considering infusion risks and cost of such outpatient treatment, ketamine infusions do not appear to be a feasible option for improving pain relief and decreasing opioid use in high-opioid requirement patients.

Cooled radiofrequency system for the treatment of chronic pain from sacroiliitis: the first case-series.

Sacroiliitis and sacroiliac (SI) joint dysfunction are frequent causes of the chronic lower back pain. Therapeutic solutions include intra-atricular injections with short-term pain relief and surgical fusion, which appears ineffective. Radiofrequency (RF) of the joint capsule or lateral branches has been previously reported with variable successes. Cooling tissue adjacent to the electrode (cooled RF) increases the radius of lesion. We present here the first retrospective data on pain relief and changes in function after such RF denervation. We reviewed electronic records of 27 patients with chronic low back pain (median 5 years) who underwent cooled RF of S1, S2, and S3 lateral branches and of dorsal ramus (DR) L5 following two diagnostic SI joint blocks (>50% of pain relief). Patient sample consisted of 20 women and 7 men, 38 to 92 years old. Pain disability index (PDI), visual analog scale (VAS) pain scores, global patient satisfaction (GPE) and opioid use before and 3-4 months after the procedure were analyzed. One patient had an incomplete chart. Observed were improvements in function (PDI) from 32.7 +/- 9.9 to 20.3 +/- 12.1 (P < 0.001) and VAS pain scores 7.1 +/- 1.6 to 4.2 +/- 2.5 (P < 0.001) at 3-4 months after the procedure. Opioid use decreased from median 30 to 20 mg morphine equivalent. Eighteen patients rated their improvement in pain scores using GPE as improved or much improved, while eight claimed minimal or no improvement. The majority of patients with chronic SI joint pain experienced a clinically relevant degree of pain relief and improved function following cooled RF of sacral lateral branches and DR of L5 at 3-4 months follow-up.

Histological changes and temperature distribution studies of a novel bipolar radiofrequency heating system in degenerated and nondegenerated human cadaver lumbar discs.

OBJECTIVE AND STUDY DESIGN: The purpose of this experimentation was to investigate the safety of a novel cooled bipolar radiofrequency system by examining histology and monitoring temperature distribution in the disc, epidural space, and adjacent to the nerve roots. In our study we used two human cadaver lumbar spines, one moderately to severely degenerated and the other mildly degenerated. SETTING AND INTERVENTIONS: Radiofrequency ablation of the disc posterior annulus is a theoretically plausible technique to ablate the nociceptors and to modify collagen of the annulus fibrosus. A novel cooled bipolar radiofrequency system is used to perform a procedure called intervertebral disc biacuplasty to heat the posterior annulus for the treatment of discogenic pain. Four lumbar intervertebral discs were treated in each spine sample using the bipolar system while two lumbar discs of each spine were used as controls. RESULTS: Temperatures developed in the posterior annulus of the disc were on average 52.35 +/- 5.07 degrees C, while in the intervertebral foramen and in the spinal canal were 38.84 +/- 1.7 degrees C and 38.29 +/- 2.04 degrees C, respectively. There was no histological evidence of damage to any other structures including vertebral end plates, epidural space, or nerve roots. Additionally, there were no histological changes in the posterior annulus that were consistent with heat-induced changes to collagen structure. CONCLUSIONS: Temperatures reached in the posterior annulus during transdiscal biacuplasty were greater than required (45 degrees C) for neuroablation. Temperatures reached at the neural foramina and epidural were low enough to avoid neural damage.

Intervertebral disc biacuplasty for the treatment of lumbar discogenic pain: results of a six-month follow-up.

OBJECTIVE: Intradiscal biacuplasty (IDB) is a novel bipolar cooled radiofrequency system for the treatment of degenerative disk disease. We present the results of a pilot trial with 6-month follow-up. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Fifteen patients, 22-55 years old, underwent one- or two-level IDB treatment of their painful lumbar discs. All had chronic low back pain >6 months, back pain exceeding leg pain, concordant pain on provocative discography, disc height >50% of control, and evidence of single- or two-level degenerative disc disease without evidence of additional changes on magnetic resonance imaging. IDB was performed under fluoroscopy using two radiofrequency probes positioned bilaterally in the intervertebral disc. Thirteen patients completed follow-up questionnaires at 1, 3, and 6 months. Pain disability was evaluated with Oswestry and Short Form (SF)-36 questionnaires. RESULTS: Median visual analog scale pain scores were reduced from 7 (95% confidence interval [CI] 6, 8) to 4 (2, 5) cm at 1 month, and remained at 3 (2, 5) cm at 6 months. The Oswestry improved from 23.3 (SD 7.0) to 16.5 (6.8) points at 1 month and remained similar after 6 months. The SF-36 Physical Functioning scores improved from 51 (18) to 70 (16) points after 6 months, while the SF-36 Bodily Pain score improved from 38 (15) to 54 (23) points. Daily opioid use did not change significantly from baseline: from 40 (95% CI 40, 120) before IDB to 5 (0, 40) mg of morphine sulfate equivalent 6 months after IDB. No procedure-related complications were detected. CONCLUSIONS: Patients showed improvements in several pain assessment measures after undergoing IDB for discogenic pain. A randomized controlled study is warranted and needed to address the efficacy of the procedure.

Botulinum toxin occipital nerve block for the treatment of severe occipital neuralgia: a case series.

Persistent occipital neuralgia can produce severe headaches that are difficult to control by conservative or surgical approaches. We retrospectively describe a series of six patients with severe occipital neuralgia who received conservative and interventional therapies, including oral antidepressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief. This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT-A) BOTOX Type A (Allergan, Inc., Irvine, CA, U.S.A.) 50 U for each block (100 U if bilateral). Significant decreases in pain Visual Analog Scale (VAS) scores and improvement in Pain Disability Index (PDI) were observed at four weeks follow-up in five out of six patients following BoNT-A occipital nerve block. The mean VAS score changed from 8 +/- 1.8 (median score of 8.5) to 2 +/- 2.7 (median score of 1), while PDI improved from 51.5 +/- 17.6 (median 56) to 19.5 +/- 21 (median 17.5) and the duration of the pain relief increased to an average of 16.3 +/- 3.2 weeks (median 16) from an average of 1.9 +/- 0.5 weeks (median 2) compared to diagnostic 0.5% bupivacaine block. Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT-A block. In conclusion, BoNT-A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics. The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time.

Value of the magnetic resonance imaging in patients with painful lumbar spinal stenosis (LSS) undergoing lumbar epidural steroid injections.

OBJECTIVES: Purpose of this study is to examine the relationship between the magnetic resonance imaging (MRI) findings, pain scores, and opiates use in patients with lumbar spinal stenosis (LSS) undergoing lumbar epidural steroid (LES) injections by retrospective review of 719 patients' electronic medical records. METHODS: Reviewed were Visual Analog Scale (VAS) pain scores and opioid use before and 8 to 12 weeks after series of LES injections. The stenosis pain index (SPI) was produced by adding an assigned numerical value of severity (1=mild, 2=moderate, 3=severe) to the number of lumbar vertebral levels affected by LSS on MRI (lateral or central). RESULTS: The average age of patients was 68.4 years. There was no relationship between the pretreatment age, sex, or number of vertebral levels affected on MRI with pretreatment VAS pain scores or opioid use. The degree of LSS present on MRI, categorized as a mild, moderate, or severe, correlated clearly with initial VAS pain scores (P=0.017). The improvement in VAS pain scores after LES injections correlated well with number of levels affected (P=0.003) and the severity of stenosis (P=0.12). Positive correlation was observed between change in VAS pain score 8 to 12 weeks after the series of LES injections and the SPI (P=0.001). There were no differences found in opioid use. DISCUSSION: The improvement in VAS pain scores after LES injections correlated well with the changes in the SPI except in those patients classified on MRI as severe LSS and more than 3 lumbar levels affected. That patient group is unlikely to benefit from LES injections.

Peripheral markers of brain damage and blood-brain barrier dysfunction.

PURPOSE: Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100beta and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100beta levels sometimes rise in the absence of neuronal damage, suggesting that S100beta is a marker of BBB rather than neuronal damage. METHODS: We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy. RESULTS: Serum S100beta increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100beta increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100beta release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100beta are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia. CONCLUSIONS: Thus, S100beta in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100beta are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.

Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6.

Loss of blood-brain barrier (BBB) function may contribute to post-ischemic cerebral injury by yet unknown mechanisms. Ischemia is associated with anoxia, aglycemia and loss of flow (i.e. shearing forces). We tested the hypothesis that loss of shear stress alone does not acutely affect BBB function due to a protective cascade of mechanisms involving cytokines and nitric oxide (NO). To determine the relative contribution of shear stress on BBB integrity we used a dynamic in vitro BBB model based on co-culture of rat brain microvascular endothelial cells (RBMEC) and astrocytes. Trans-endothelial electrical resistance (TEER), IL-6 release and NO levels were measured from the lumenal and ablumenal compartments throughout the experiment. Flow-exposed RBMEC were challenged with 1 h of normoxic-normoglycemic flow cessation (NNFC) followed by reperfusion for 2 to 24 h. NNFC caused a progressive drop in nitric oxide production during flow cessation followed by a time-dependent increase in ablumenal IL-6 associated with a prolonged NO increase during reperfusion. The nitric oxide synthetase (NOS) inhibitor L-NAME (10 microM) abrogated all effects of NNFC, including changes in NO and cytokine production. BBB permeability did not increase during or after NNFC/reperfusion, but was increased by treatment with L-NAME or when the effects of IL-6 were blocked. Flow adapted RBMEC and astrocytes respond to NNFC/reperfusion by overproduction of IL-6, possibly secondary to increased production of NO during the reperfusion. Maintenance of BBB function during and following NNFC appears to depend on intact NO signaling and IL-6 release.