Neuropathic pain: emerging treatments

Neuropathic pain remains one of the most challenging of all neurological diseases and presents a large unmet need for improved therapies. Many mechanistic details are still lacking, but greater knowledge of overlapping mechanisms and disease comorbidities has highlighted key areas for intervention. These include peripheral and central hyperexcitability. Among the molecular drivers are ion channels (Nav1.7, Nav1.8, Nav1.3, Cav2.2, and alpha2-delta subunits) whose expression is changed during neuropathic pain and their block shows therapeutic utility. Block of a number of ligand-gated channels [transient receptor potential (TRP)V1, TRPM8, and neuronal nicotinic receptors (NNRs)], important in neural sensitization, may also prove beneficial. Other approaches, such as the modulation of peripheral excitability via CB1 receptors, reduction of spinal excitability through block of glutamate receptors (metabotropic glutamate receptor 5 and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate), block of activated spinal neuroglial (CCR2 and P2X7), or increasing spinal inhibition by enhancing monoaminergic activity, all offer exciting opportunities currently being validated in the clinic. Finally of note is the emergence of biological approaches, for example, antibodies, siRNA, gene therapy, offering powerful therapeutic additions with which to redress the neurological disease imbalances causing neuropathic pain.     

The emerging pattern of pediatric day-care surgery

The utilization of short stay surgical facilities is increasing and indications for day-care surgery for children are becoming more diverse. These trends were observed in a review of day-care surgery performed at British Columbia Children's Hospital during the years 1982 to 1986. During 1984 and 1985, 688 hernia repairs were undertaken, as were 76 anorectal procedures such as anal fistulotomy, drainage of abscesses, etc. In addition, 127 orchidopexies were performed, which indicated a 40% increase when compared with earlier years. Further procedures included the excision of 38 branchial cleft anomalies and 17 salivary gland lesions, as well as the performance of 95 tracheobronchial endoscopies including the removal of 25 foreign bodies. Head and neck and endoscopic procedures now represent 21% of all general surgery day care cases, and have increased by 50% since 1982. Thirty-six children (1.6%) initially brought in for day care surgery required actual admission to the hospital for such reasons as (1) the procedure being more complex than initially anticipated (15 patients); (2) hemorrhage (5 patients); or (3) postanesthetic concern (11 patients). Two thirds of the anesthetic complications were in infants less than 3 months of age. A special subgroup of high-risk infants were identified--the previous premature less than 52 weeks conceptual age. In our opinion, infants who are less than 3 months of age, especially if born prematurely, should be admitted to the hospital for surgery.     

Cardorenal syndrome: an emerging problem in pediatric critical care

The cardiorenal syndrome (CRS) refers to a complex pathophysiologic state in which heart and kidney dysfunction coexist. Although a robust amount of adult literature exists, limited reports have been made regarding CRS in pediatric patients. However, CRS is increasingly being recognized as an impactful clinical problem that can have important implications regarding the need for treatment and prognosis. Although wide acceptance of a unified definition of CRS is lacking, a general consensus exists that CRS can be either primarily caused by cardiac disease with secondary effects on the kidney, or vice versa, as well as systemic conditions in which cardiac and renal disease are both considered to be secondary. Convincing data in the pediatric perioperative population have been reported, but there is a paucity of information in acute and chronic heart failure (HF), as well as acute kidney injury (AKI) and chronic kidney disease (CKD). Herein, we briefly report on the adult literature and summarize the current pediatric experience.     

From pain research to pain treatment: the role of human experimental pain models

There is no objective measure of a complete pain perception; we can, however, measure different aspects of nociceptive processing and pain perception. Earlier, experimental pain models often only involved induction of cutaneous pain using a single stimulus modality. Recently new experimental models have been developed eliciting various modalities of deep and visceral pain which more closely resemble clinical pain conditions. It is imperative to use multi-modal and multi-structure pain induction and assessment techniques, because a simple model cannot describe the very complex and multi-factorial aspects of clinical pain. Furthermore, it is important to assess pain under normal and pathophysiological conditions.The importance of peripheral and central hyperexcitability for acute and chronic pain has been demonstrated in animals and, to some extent, in humans. However, in spite of our immense knowledge, we still do not know how to prevent and treat this hyperexcitability efficiently. Our understanding of nociceptive mechanisms involved in acute and chronic pain and the effects of anaesthetic drugs or combinations of drugs on these mechanisms in humans may also be expanded using human experimental models. This mechanism-based approach may help us to develop and test therapeutic regimes in patients with acute and chronic pain.     

Organization of pain management services

Pain is ubiquitous and is common throughout healthcare. Appropriate and timely pain treatment and management is a human right. The knowledge and skills needed to deliver pain treatments should not be confined to specialized centres. It is the duty of all clinicians irrespective of profession to be able to treat patients who suffer with pain. Pain Services should be organized to deliver assessment and treatment for the patient in pain in a timely fashion and in the appropriate place. This may well be in the community or primary care setting as well as in secondary or tertiary care. The treatment of chronic pain can present a significant challenge. Patients often present with complex problems and may need the expertise of a multi-professional team with skills in diagnostics, specific pain therapies, rehabilitation and psychological counselling. Some centres have developed a ‘central intake’, which is designed to ensure that patients referred to the service receive tailored assessment and treatment delivered by the most appropriate healthcare professional and, where possible in their community.     

Organization of pain management services

Historically, pain services have been poorly integrated into hospital management systems and allocated relatively poor resources. Institutions differ in their needs and complexity, ranging from single modality clinics to large interdisciplinary facilities offering complex treatment including psychological rehabilitation and implantation technologies. The organizational needs of these services differ substantially. Organization has to be considered at three levels: within the department, within the organization, and within the health system. Departmental organization should consider a common management structure for all the interdisciplinary team, including the administrative and clerical staff. The clinical leader of the service need not be a doctor, but must have a job plan that includes sufficient time for necessary managerial tasks. Within a Trust or hospital, the pain service should have the same weighting as other clinical departments and the same resources available. The need for close links with other departments (e.g. orthopaedics, oncology) requires active cooperation between different directorates. Joint clinics can tax organizational systems but can be an effective way of managing patients with complex problems. Chronic pain poses a significant burden on the health care system. Increasing focus on chronic disease management by the production of guidelines and service frameworks for conditions such as diabetes and asthma have done little for the substantial number of people disabled by chronic pain. If pain services are to have a significant impact on chronic painful conditions they have to develop closer ties with primary care and health planning authorities. Such a move would see pain services being as much about education, training and development of policy as simply providing clinical care.     

Patellofemoral pain in the pediatric patient.

The pediatric extensor mechanism is subject to a variety of congenital, developmental, and traumatic disorders. Growth related factors modulate the development of patellofemoral pathomechanics. Injuries to periarticular soft tissues, apophyseal, epiphyseal, and articular cartilage are identified by meticulous history and physical examination. Diagnostic radiographs and MR imaging are invaluable adjuncts. Specific rehabilitative programs are very effective and lead to a high degree of clinical success.     

A survey of directors of Canadian academic acute pain management services: the nursing team members role — a brief report

PURPOSE: The purpose of this study was to identify Canadian academic centres with Acute Pain Management Service (APMS), and to describe the nature of nursing involvement on the APMS. METHODS: Departments of Anesthesiology in the 16 Canadian medical schools were contacted to obtain a list of affiliated hospitals and the person most responsible for acute pain. A questionnaire designed to gain insight into nursing involvement on APMS was sent out to the 62 hospitals between June 2000 and January 2001. RESULTS: Seventy-six percent of centres responded and of these 89% (n = 42) had an APMS. In 76% of APMS nursing was involved on the service. Sixty-two percent (n = 26) had a designated nursing team member on the APMS who contributed in the realms of patient care, staff and patient education, and administrative development. The APMS nurse performed patient rounds independently (62%) and with a physician (64%). Decision-making was primarily the responsibility of anesthesiology, however, the APMS nurse (38%) and the bedside nurse (23%) were involved in some centres. The highest educational attainment in the 26 hospitals with an APMS nurse was, diploma RN (27%), BScN (31%) and MSc (12%). The distribution of advance practice nursing was nurse practitioner (12%), clinical nurse specialist (27%), or both (8%). CONCLUSION: Nursing played an important role on the APMS, however, quality acute pain management can only be achieved with continuing efforts by anesthesiology, nursing and hospital administration to support the role of nurses as essential members of the acute pain team.     

Rectus sheath block: successful use in the chronic pain management of pediatric abdominal wall pain

Seven pediatric patients (aged 11-16 years) with chronic abdominal wall pain are presented who gained significant relief from a rectus sheath block (RSB). We describe the case histories and review the relevant literature for this technique. The etiology of the abdominal wall pain was considered to be abdominal cutaneous nerve entrapment, iatrogenic peripheral nerve injury, myofascial pain syndrome or was unknown. All patients showed significant initial improvement in pain and quality of life. Three patients required only the RSB to enable them to be pain-free and return to normal schooling and physical activities. Two children received complete relief for more than 1 year. In the majority of cases, the procedure was carried out under general anesthesia as a daycase procedure. Local anesthetic and steroids were used. This is the first report of the successful use of this technique in the chronic pain management setting in children.     

Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate

Calciphylaxis–calcific uremic arteriolopathy, is a serious disorder of arteriolar calcification of the arteriole media and is associated with endovascular fibrosis and thrombosis in subcutaneous adipose tissue. It frequently results in severe ischemia, intense pain, and tissue necrosis with nonhealing skin ulcerations. It usually occurs in chronic kidney disease and especially in patients requiring renal replacement therapy. It is associated with a very high mortality rate, and the number of reports and reviews seemed to have increased over the past 5 years. Advances in therapy and salvaging patients from this high mortality risk have recently been reported with the use of sodium thiosulfate. The new application for this old drug used to treat cyanide poisoning and recently preventing neurotoxic effects resulting in hearing loss in those patients with head and neck cancer receiving cisplatin and carboplatin therapy are discussed. Recently, multiple case reports have demonstrated that sodium thiosulfate therapy has resulted in rapid pain relief, healing of skin ulcerations, and prevention of high mortality risk. This emerging treatment and its success are relatively unknown to many physicians. The purpose of this report is to share with others the emerging role of sodium thiosulfate and its new application as a treatment option to be used in combination with other treatment modalities for calciphylaxis–calcific uremic arteriolopathy. Indeed, as with any new treatment this emerging therapy should be studied in greater detail, but this old drug seems to have a new life in the hands of treating physicians.     

Cardiovascular disease after transplantation: an emerging role of the immune system

Cardiovascular disease (CVD) after transplantation remains a major concern. Little is known about what drives the increased cardiovascular risk in transplant recipients apart from traditional risk factors. The immune system is involved in the pathogenesis of hypertension, atherosclerosis, and coronary artery disease in the general population. Recently, inhibition of interleukin 1 ? β by canakinumab versus placebo decreased the incidence of cardiovascular events. Emerging evidence points to a role of adaptive cellular immunity in the development of CVD. Especially, expansion of pro‐inflammatory and antiapoptotic cytotoxic CD 4⁺CD 28^null T cells is closely associated with incident CVD in various study populations including transplant recipients. The association of cytomegalovirus exposure with increased cardiovascular mortality might be explained by its capacity to upregulate these cytotoxic cells. Also, humoral immunity seems to be relevant for cardiovascular outcome in transplant recipients. Panel‐reactive antibodies at baseline and donor‐specific antibodies are independently associated with poor cardiovascular outcome after kidney transplantation. Cardiovascular effects of immunosuppressive drugs and statins do not only imply indirect positive or negative effects on traditional cardiovascular risk factors but also intrinsic immunological effects. How immunosuppressive drugs modify atherosclerosis largely remains elusive.     

Postoperative pain management in pediatric patients undergoing minimally invasive repair of pectus excavatum: The role of intercostal block

Purpose

There are no published data regarding value of intercostal block following pectus excavatum repair. Our aim was to evaluate the efficacy of intercostal block in children following minimally invasive repair of pectus excavatum (MIRPE).

Methods

Forty-five patients given patient-controlled analgesia (PCA) with morphine postoperatively were studied. Twenty-six patients were given bilateral intercostal blocks after induction of anesthesia (PCA-IB group), and nineteen patients were retrospective controls without regional blockade (PCA group). All patients were followed up 24 h postoperatively.

Results

A loading dose of morphine (0,1 ± 0,49 mg/kg) before starting PCA was used in seventeen patients in PCA group vs. no patient in PCA-IB group. Cumulative used morphine doses were lower up to 12 h after surgery in PCA-IB group (0,29 ± 0,08 μg/kg) than in the PCA group (0,46 ± 0,18 μg/kg), p < 0,01. There were no differences in pain scores, oxygen saturation values, sedation scores, and the incidence of pulmonary adverse events between the two groups. There was a tendency towards less morphine-related adverse effects in PCA-IB group compared to PCA group (p < 0,05). No complications related to the intercostal blocks were observed.

Conclusion

Bilateral intercostal blocks following MIRPE are safe and easy to perform and can diminish postoperative opioid requirement. Double-blind randomized study is required to confirm the potential to diminish opioid related side effects.