A Literature Review: The Mechanisms and Treatment of Neuropathic Pain-A Brief Discussion.

Classically, neuropathic pain is described as a pain caused by a lesion or disease of the somatosensory system. However, one must note that the presence of somatosensory pathology alone does not guarantee a progression to neuropathic pain. This is due, in part, to the fact that neuropathic pain is a notoriously complex disease process, involving sensitization of both the central and peripheral nervous systems. Its causes are also numerous and varied, including trauma, the compression of a nerve, autoimmune disorders, diabetes, and infections. Due to the various manifestations, causes, and symptoms of neuropathic pain, the treatment of this disease process has proved challenging for generations of physicians. This section aims to elaborate on newly proposed mechanisms for pharmacological and targeted therapies, such as neurostimulation, which aim to reduce the negative somatosensory effects of neuropathic pain.

Subanesthetic ketamine: the way forward for pain management in sickle cell disease patients?

INTRODUCTION: Patients with sickle cell disease (SCD) present recurrent episodes of acute pain, the hallmark of the disease, and some will also develop chronic pain. Currently, the treatment of SCD acute pain only targets its symptoms, rather than underlying mechanisms, and is directed by expert and consensus guidelines. AREAS COVERED: While opioids remain the mainstay of therapy for acute pain and are also used to treat SCD-related chronic pain, in some patients, opioids are ineffective or are associated with severe undesirable side effects. In those instances, clinicians caring for patients with SCD face an unmet need for effective non-opioid analgesics. Recently, the use of subanesthetic ketamine has been explored as a strategy to meet this need. While definitive evidence of its efficacy is lacking, some information exists suggesting that subanesthetic ketamine improves pain control and may have opioid-sparing effects in SCD-related acute pain. However, ketamine can also yield undesirable psychotomimetic and cardiovascular effects. EXPERT OPINION: After weighing potential risks and benefits, in the absence of better alternatives and in settings where it can be administered safely, ketamine may be a reasonable option for patients with SCD-related acute refractory pain.

Demand-only patient-controlled analgesia for treatment of acute vaso-occlusive pain in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic illness that is associated with frequent admissions for vaso-occlusive episodes (VOE). Opioids are frequently utilized in pain management, but dosing is often provider dependent. Opioids cause both short-term and long-term side effects, so the minimal effective dose is desired. This study examined demand-only patient-controlled analgesia (PCA) in pediatric patients. METHODS: A new clinical practice guideline (CPG) for a single institution was implemented, which eliminated basal infusion dosing for PCAs on hospital admission. The primary aim of this retrospective study was to evaluate length of stay (LOS) before and after implementation of a CPG of demand-only PCA and, in a selected subpopulation, addition of short-term methadone. Secondary aims included opioid utilization, acute chest syndrome (ACS), and hypoxia. Inclusion criteria included SCD, ≤21 years of age, uncomplicated VOE admission, and ≥ 3 and ≤ 8 hospital admissions for SCD pain control within one calendar year. RESULTS: LOS decreased postintervention (7.2 ± 5.1 vs 4.5 ± 3.8 days, P < 0.001). Mean total opioid utilization in morphine equivalents mg/kg markedly decreased between the cohorts (13.3 ± 33.8 vs 3.6 ± 3.0, P < 0.001). ACS (21.9% vs 2.8%, P = 0.004) and hypoxia (28% vs 6.9%, P< 0.001) decreased significantly as well. CONCLUSION: Bolus PCA dosing of opioids resulted in decreased LOS and reductions in opioid utilization, hypoxia, and ACS.

Alleviating Terminal Pediatric Cancer Pain.

Terminal cancer pain remains one of the most distressing aspects of pediatric oncology practice. Opioids are the cornerstone of cancer pain management at end-of-life and fortunately, most pain at end-of-life can be managed successfully. This article presents a practical step-by-step approach to alleviating pediatric terminal cancer pain, which can be delivered across settings.

Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis.

Sickle Cell Disease (SCD) is a chronic hemolytic disorder associated with frequent pain episodes, end organ damage and a shortened lifespan. Currently there exist no disease specific targeted therapies for the treatment of acute vaso-occlusive crisis (VOC) and management with analgesics and hydration is purely supportive. Improvement in understanding of disease pathophysiology has resulted in a great interest in disease modifying novel therapies and many are being evaluated in clinical trials. Here we report the results from the pre-specified mid-point analysis of the Phase 2 study of Intravenous Gamma Globulin (IVIG) for the treatment of acute VOC in patients with SCD and lessons learned.

Intraoperative intravenous ibuprofen use is not associated with increased post-tonsillectomy bleeding.

OBJECTIVES: Intravenous (IV) ibuprofen was approved by the FDA for use in pediatric patients in November 2015. The objective of this study was to compare bleeding rates in pediatric tonsillectomy patients who received intraoperative intravenous ibuprofen versus those who did not. Secondary objectives included analyzing factors that correlated with return to the Emergency Department (ED) for pain or dehydration. METHODS: Charts were reviewed for all patients 0-18 years of age who underwent a tonsillectomy with or without adenoidectomy at a tertiary care children's hospital from 1/1/2017 through 5/21/2018. Demographic information and perioperative medications including the use of intraoperative intravenous ibuprofen were recorded. ED visits and operating room (OR) returns for bleeding were tracked for up to 30 days after surgery. RESULTS: 1085 charts were analyzed. Intraoperative IV ibuprofen was used in 132 cases (12.2%). Primary bleeds, defined as bleeding within 24 h of surgery, occurred in 1 (0.76%) of 132 patients who received IV ibuprofen, and 1 (0.10%) of 953 patients who did not receive IV ibuprofen. Secondary bleeds, defined as bleeds after 24 h from surgery occurred in 2 (1.52%) of 132 patients who received IV ibuprofen and 38 (3.99%) of 953 patients who did not receive IV ibuprofen. No statistical difference was found between the two groups in rates of overall (primary plus secondary) bleeding requiring return to ED (p = 0.759) or return to OR (p = 0.710). CONCLUSION: The observed bleeding rate after pediatric tonsillectomy was not statistically different in patients who received intraoperative IV ibuprofen versus those who did not receive this medication. LEVEL OF EVIDENCE: III.

A Randomized Trial of Yoga for Children Hospitalized With Sickle Cell Vaso-Occlusive Crisis.

CONTEXT: Sickle cell disease (SCD) vaso-occlusive crisis (VOC) remains an important cause of acute pain in pediatrics and the most common SCD complication. Pain management recommendations in SCD include nonpharmacological interventions. Yoga is one nonpharmacological intervention that has been shown to reduce pain in some populations; however, evidence is lacking in children with VOC. OBJECTIVES: The primary objective of this study was to compare the effect of yoga vs. an attention control on pain in children with VOC. The secondary objectives were to compare the effect of yoga vs. an attention control on anxiety, lengths of stay, and opioid use in this population. METHODS: Patients were eligible if they had a diagnosis of SCD, were 5-21 years old, were hospitalized for uncomplicated VOC, and had an admission pain score of ≥7. Subjects were stratified based on disease severity and randomized to the yoga or control group. RESULTS: Eighty-three percent of patients approached (N = 73) enrolled on study. There were no significant differences in baseline clinical or demographic factors between groups. Compared with the control group, children randomized to yoga had a significantly greater reduction in mean pain score after one yoga session (-0.6 ± 0.96 vs. 0.0 ± 1.37; P = 0.029). There were no significant differences in anxiety, lengths of stay, or opioid use between the two groups. CONCLUSION: This study provides evidence that yoga is an acceptable, feasible, and helpful intervention for hospitalized children with VOC. Future research should further examine yoga for children with SCD pain in the inpatient and outpatient settings.

Opioid-Induced Hyperalgesia: A Diagnostic Dilemma.

Opioids are utilized frequently for the treatment of moderate to severe acute pain in the perioperative setting, as well as in the treatment of cancer-related pain. When prescribing chronic opioid therapy to patients with chronic pain, it is crucial for the practitioner to be aware not only of the issues of tolerance and withdrawal, but also to have knowledge of the possibility for opioid-induced hyperalgesia (OIH). An understanding of the differences between tolerance and OIH when escalating opioid therapy allows the titration of opioid as well as nonopioid analgesics in order to obtain maximum control of both chronic and acute pain. A case study is described to highlight the importance of judicious utilization of opioids in the treatment of cancer-related pain. In this case, high-dose opioid therapy did not improve chronic pain and contributed to a hyperalgesic state in which a young man experienced severe intractable pain postoperatively after two routine thoracotomies, despite aggressive pharmacologic measures to manage his perioperative pain. Furthermore, it illustrates the potential advantages of opioid rotation to methadone when OIH is suspected.

Intrathecal analgesia: time to consider it for your patient?

When systemic analgesics or antispasmodics fail to control chronic pain or cause intolerable adverse effects, an intrathecal drug delivery system may be the best bet.

Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.

Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function.

Children and adolescents with complex regional pain syndrome: more psychologically distressed than other children in pain?

BACKGROUND: Historically, in both adult and pediatric populations, a lack of knowledge regarding complex regional pain syndrome (CRPS) and absence of clear diagnostic criteria have contributed to the view that this is a primarily psychiatric condition. OBJECTIVE: To test the hypothesis that children with CRPS are more functionally disabled, have more pain and are more psychologically distressed than children with other pain conditions. METHODS: A total of 101 children evaluated in a tertiary care pediatric pain clinic who met the International Association for the Study of Pain consensus diagnostic criteria for CRPS participated in the present retrospective study. Comparison groups included 103 children with abdominal pain, 291 with headache and 119 with back pain. Children and parents completed self-report questionnaires assessing disability, somatization, pain coping, depression, anxiety and school attendance. RESULTS: Children with CRPS reported higher pain intensity and more recent onset of pain at the initial tertiary pain clinic evaluation compared with children with other chronic pain conditions. They reported greater functional disability and more somatic symptoms than children with headaches or back pain. Scores on measures of depression and anxiety were within normal limits and similar to those of children in other pain diagnostic groups. CONCLUSIONS: As a group, clinic-referred children with CRPS may be more functionally impaired and experience more somatic symptoms compared with children with other pain conditions. However, overall psychological functioning as assessed by self-report appears to be similar to that of children with other chronic pain diagnoses. Comprehensive assessment using a biopsychosocial framework is essential to understanding and appropriately treating children with symptoms of CRPS.