Pharmacotherapy to Manage Central Post-Stroke Pain.

Central post-stroke pain is a chronic neuropathic pain syndrome following a cerebrovascular accident. The development of central post-stroke pain is estimated to occur in 8 to 55% of stroke patients and is described as constant or intermittent neuropathic pain accompanied by dysesthesia of temperature and/or pressure sensations. These pain and sensory deficits are within the area of the body corresponding to the stroke lesion. The onset of pain is usually gradual, though it can develop either immediately after stroke or years after. Given the diversity in its clinical presentation, central post-stroke pain is a challenging diagnosis of exclusion. Furthermore, central post-stroke pain is often resistant to pharmacological treatment options and a clear therapeutic algorithm has not been established. Based on current evidence, amitriptyline, lamotrigine, and gabapentinoids should be used as first-line pharmacotherapy options when central post-stroke pain is suspected. Other drugs, such as fluvoxamine, steroids, and Intravenous infusions of lidocaine, ketamine, or even propofol, can be considered in intractable cases. In addition, interventional therapies such as motor cortex stimulation or transcranial magnetic stimulation have been shown to provide relief in difficult-to-treat patients.

Cognitive flexibility and persistent post-surgical pain: the FLEXCAPP prospective observational study.

BACKGROUND: Impaired performance on tasks assessing executive function has been linked to chronic pain. We hypothesised that poor performance on tests assessing the ability to adjust thinking in response to changing environmental stimuli (cognitive flexibility) would be associated with persistent post-surgical pain. METHODS: We conducted a single-centre prospective observational study in two perioperative cohorts: patients undergoing total knee arthroplasty or noncardiac chest surgical procedures. The co-primary outcome measures compared preoperative performance on the Trail Making Test and the colour-word matching Stroop test between patients who developed persistent post-surgical pain and those who did not. Secondary outcome measures included the associations between these test scores and pain severity at 6 months. RESULTS: Of 300 participants enrolled, 198 provided 6 month follow-up data. There were no significant differences in preoperative Trail Making Test B minus A times (33 vs 34 s; P=0.59) or Stroop interference T-scores (47th vs 48th percentile; P=0.50) between patients with and without persistent post-surgical pain (primary outcome). Of those who reported persistent post-surgical pain, poorer baseline performance on the colour-word matching Stroop test was associated with higher pain scores at 6 months in both knee arthroplasty (r=-0.32; P=0.04) and chest (r=-0.44; P=0.02) surgeries (secondary outcome). CONCLUSIONS: Preoperative cognitive flexibility test performance was not predictive of overall persistent post-surgical pain incidence 6 months after surgery. However, poor performance on the colour-word matching Stroop test was independently associated with more severe persistent post-surgical pain in both cohorts. CLINICAL TRIAL REGISTRATION: NCT02579538.

Physical therapy management, surgical treatment, and patient-reported outcomes measures in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome.

OBJECTIVE: To assess the results of physical therapy management and surgical treatment in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome (NTOS) using patient-reported outcomes measures. METHODS: Of 183 new patient referrals from July 1 to December 31, 2015, 150 (82%) met the established clinical diagnostic criteria for NTOS. All patients underwent an initial 6-week physical therapy trial. Those with symptom improvement continued physical therapy, and the remainder underwent surgery (supraclavicular decompression with or without pectoralis minor tenotomy). Pretreatment factors and 7 patient-reported outcomes measures were compared between the physical therapy and surgery groups using t-tests and χ2 analyses. Follow-up results were assessed by changes in 11-item version of Disability of the Arm, Shoulder, and Hand (QuickDASH) scores and patient-rated outcomes. RESULTS: Of the 150 patients, 20 (13%) declined further treatment or follow-up, 40 (27%) obtained satisfactory improvement with physical therapy alone, and 90 (60%) underwent surgery. Slight differences were found between the physical therapy and surgery groups in the mean ± standard error degree of local tenderness to palpation (1.7 ± 0.1 vs 2.0 ± 0.1; P = .032), the number of positive clinical diagnostic criteria (9.0 ± 0.3 vs 10.1 ± 0.1; P = .001), Cervical-Brachial Symptom Questionnaire scores (68.0 ± 4.1 vs 78.0 ± 2.7; P = .045), and Short-Form 12-item physical quality-of-life scores (35.6 ± 1.5 vs 32.0 ± 0.8; P = .019) but not other pretreatment factors. During follow-up (median, 21.1 months for physical therapy and 12.0 months for surgery), the mean change in QuickDASH scores for physical therapy was -15.6 ± 3.0 (-29.5% ± 5.7%) compared with -29.8 ± 2.4 (-47.9% ± 3.6%) for surgery (P = .001). The patient-rated outcomes for surgery were excellent for 27%, good for 36%, fair for 26%, and poor for 11%, with a strong correlation between the percentage of decline in the QuickDASH score and patient-rated outcomes (P < .0001). CONCLUSIONS: The present study has demonstrated contemporary outcomes for physical therapy and surgery in a well-studied cohort of patients with NTOS, reinforcing that surgery can be effective when physical therapy is insufficient, even with substantial pretreatment disability. Substantial symptom improvement can be expected for ∼90% of patients after surgery for NTOS, with treatment outcomes accurately reflected by changes in QuickDASH scores. Within this cohort, it was difficult to identify specific predictive factors for individuals most likely to benefit from physical therapy alone vs surgery.

How central is central poststroke pain? The role of afferent input in poststroke neuropathic pain: a prospective, open-label pilot study.

Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying mechanisms of which are not well understood. It has been suggested that stroke-associated loss of inhibitory neurons in the spinothalamic tract causes disinhibition of thalamic neurons, which autonomously generate ectopic nociceptive action potentials responsible for the pain experience. We hypothesized that CPSP is a result of misinterpretation of afferent sensory input by the sensitized neurons within the brain, rather than generated spontaneously by the damaged central nervous system (CNS) neurons. To test this hypothesis, we prospectively recruited 8 patients with definite CPSP affecting at least 1 extremity. In an open-label intervention, an ultrasound-guided peripheral nerve block with lidocaine was performed to block afferent sensory input from a painful extremity. Spontaneous and evoked pain, neuropathic pain descriptors, and lidocaine plasma concentrations were measured. The blockade of peripheral sensory input resulted in complete abolition of pain in 7 of the 8 subjects within 30 minutes (the primary outcome measure of the study), and >50% pain relief in the remaining participant. Median (interquartile range) spontaneous pain intensity changed from 6.5 (4.3-7.0) at baseline to 0 (0-0) after the block (P = 0.008). All mechanical/thermal hypersensitivity was abolished by the nerve block. The results suggest that it is unlikely that CPSP is autonomously generated within the CNS. Rather, this pain is dependent on afferent input from the painful region in the periphery, and may be mediated by misinterpretation of peripheral sensory input by sensitized neurons in the CNS.

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial.

INTRODUCTION: Epidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade, has a multitude of additional potential benefits, from decreasing the incidence of postoperative delirium to reducing the development of persistent postsurgical pain (PPSP). Prior studies have also identified a correlation between the use of epidural analgesia and improved oncological outcomes and survival. The aim of this study is to evaluate the effect of epidural analgesia in pancreatic operations on immediate postoperative outcomes, the development of PPSP and oncological outcomes in a prospective, single-blind, randomised controlled trial. METHODS: The Epidurals in Pancreatic Resection Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled trial. 150 patients undergoing either pancreaticoduodenectomy or distal pancreatectomy will be randomised to receive an epidural bupivacaine infusion following anaesthetic induction followed by continued epidural bupivacaine infusion postoperatively in addition to the institutional standardised pain regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and ketorolac (intervention group) or no epidural infusion and only the standardised postoperative pain regimen (control group). The primary outcome was the postoperative opioid consumption, measured in morphine or morphine-equivalents. Secondary outcomes include patient-reported postoperative pain numerical rating scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)-1ß, IL-6, tumour necrosis factor-α, IL-10), occurrence of postoperative delirium, development of PPSP as determined by quantitative sensory testing, and disease-free and overall survival. ETHICS AND DISSEMINATION: The E-PRO trial has been approved by the institutional review board. Recruitment began in May 2016 and will continue until the end of May 2018. Dissemination plans include presentations at scientific conferences and scientific publications. TRIAL REGISTRATION NUMBER: NCT02681796.

Associations between clinical diagnostic criteria and pretreatment patient-reported outcomes measures in a prospective observational cohort of patients with neurogenic thoracic outlet syndrome.

OBJECTIVE: Neurogenic thoracic outlet syndrome (NTOS) is caused by dynamic compression of the brachial plexus at the level of the supraclavicular scalene triangle or the subcoracoid (pectoralis minor) space, or both. The purpose of this study was to characterize relationships between 14 clinical diagnostic criteria (CDC) and seven pretreatment patient-reported outcomes measures (PROMs) in a prospective cohort of patients with NTOS. METHODS: There were 183 new patient referrals between July 1 and December 31, 2015, with 150 (82%) meeting an established set of predefined CDC for NTOS. PROMs were evaluated across five domains: pain severity, functional disability, depression, quality of life, and pain catastrophizing. Linear regression and Pearson correlation statistics were used to analyze associations between CDC and PROMs. RESULTS: Mean ± standard error patient age was 37.1 ± 1.1 years (range, 12-66 years), and 107 (71%) were women. Five (3%) had a cervical rib, and 15 (10%) had recurrent NTOS. The most frequently positive CDC were neck or upper extremity pain (99%), upper extremity or hand paresthesia (94%), symptom exacerbation by arm elevation (97%), localized supraclavicular or subcoracoid tenderness to palpation (96%), and a positive 3-minute elevated arm stress test (94%; mean duration, 102.0 ± 5.1 seconds). The number of positive CDC (mean, 9.6 ± 0.1) correlated with the degree of tenderness to palpation and the duration of elevated arm stress test, as well as with PROMs for pain severity, functional disability, depression, physical quality of life, and pain catastrophizing (all P < .0001). PROMs across multiple domains were also strongly correlated with each other. Patients with clinically significant pain catastrophizing exhibited a greater level of functional disability than noncatastrophizing patients (P < .0001). CONCLUSIONS: This study illustrates the relative strengths of 14 CDC and seven PROMs to evaluate patients with NTOS, helping validate the selected CDC and highlighting the potential role of pain catastrophizing in functional disability. This cohort will provide valuable information on the utility of different CDC and PROMs to predict treatment outcomes.

Current perspectives on intrathecal drug delivery.

Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes.

The effect of nitrous oxide anesthesia on early postoperative opioid consumption and pain.

BACKGROUND AND OBJECTIVES: Many patients experience moderate to severe postoperative pain. Nitrous oxide (N2O) exerts analgesia by inhibition of N-methyl-D-aspartate receptors. Ketamine, another N-methyl-D-aspartate receptor antagonist, reduces postoperative opioid consumption and pain. A similar effect of N2O is plausible, yet understudied. The goal of this study was to determine the effects of N2O anesthesia on early postsurgical opioid consumption and pain. METHODS: This was a retrospective, secondary analysis of the Vitamins In Nitrous Oxide trial, where 500 patients undergoing general anesthesia for noncardiac surgery received 60% N2O and 125 received no N2O (otherwise, inclusion/exclusion criteria were identical). Exclusion criteria for this study were regional anesthesia, not extubated after surgery, transfer to intensive care unit, no available postanesthesia care unit record, postsurgical sedation, or treated with naloxone. Primary outcomes were cumulative opioid consumption measured in morphine equivalents and pain scores during the immediate recovery phase. RESULTS: Four hundred forty-two patients met inclusion criteria. No difference in intraoperative and postoperative opioid consumption was observed between patients who received N2O (n = 353) and patients who did not (n = 89). The median [interquartile range] postoperative morphine equivalent dose was 6.7 mg [1.7-14.1 mg] for patients who received N2O and 6.7 mg [2.1-15.4 mg] for patients who did not (P = 0.73). The maximum pain score was 6 [4-8] for patients who received N2O versus 6 [3-8] for patients who received N2O-free anesthesia (P = 0.52). The prevalence of moderate to severe pain was 69% for patients who received N2O and 68% for patients who did not (P = 0.90). CONCLUSIONS: Nitrous oxide anesthesia was not associated with decreased opioid administration, pain, or incidence of moderate to severe pain in the early postoperative phase.

Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy.

Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon.

Estimation of the bispectral index by anesthesiologists: an inverse turing test.

BACKGROUND: Processed electroencephalographic indices, such as the bispectral index (BIS), are potential adjuncts for assessing anesthetic depth. While BIS® monitors might aid anesthetic management, unprocessed or nonproprietary electroencephalographic data may be a rich source of information for clinicians. We hypothesized that anesthesiologists, after training in electroencephalography interpretation, could estimate the index of a reference BIS as accurately as a second BIS® monitor (twin BIS®) (Covidien Medical, Boulder, CO) when provided with clinical and electroencephalographic data. METHODS: Two sets of electrodes connected to two separate BIS® monitors were placed on the foreheads of 10 surgical patients undergoing general anesthesia. Electroencephalographic parameters, vital signs, and end-tidal anesthetic gas concentrations were recorded at prespecified time points, and were provided to two sets of anesthesiologists. Ten anesthesiologists received brief structured training in electroencephalograph interpretation and 10 were untrained. Although electroencephalographic waveforms and open-source processed electroencephalograph metrics were provided from the reference BIS®, both groups were blinded to BIS values and were asked to estimate BIS. RESULTS: The trained anesthesiologists averaged as close to or closer to the reference BIS® compared with the twin BIS® monitor for 34% of their BIS estimates versus 26% for the untrained anesthesiologists. Using linear mixed effects model analysis, there was a statistically significant difference between the trained and untrained anesthesiologists (P = 0.02), but no difference between the twin BIS® monitor and trained anesthesiologists (P = 0.9). CONCLUSION: With limited electroencephalography training and access to clinical data, anesthesiologists can estimate the BIS almost as well as a second BIS® monitor. These results reinforce the potential utility of training anesthesia practitioners in unprocessed electroencephalogram interpretation.