Does work have to be so painful? A review of the literature examining the effects of fibromyalgia on the working experience from the patient perspective.

BACKGROUND: Chronic pain conditions, such as fibromyalgia, adversely affect individuals' abilities to work. AIM: The aim of this study was to examine, from the perspective of patients, the effects that fibromyalgia symptoms had on their ability to work, the challenges that they encountered in the workplace that did not foster their continued employment, and the types of modifications to their work or workplace that they thought would facilitate their productivity and ability to work. METHODS: A scoping review method, applying techniques of systematic review, was used to conduct a research synthesis of the literature regarding fibromyalgia and work that looked at this issue from the patient perspective. RESULTS: A variety of themes emerged from the analysis and could be broadly categorized into (1) the work experience was a challenging one with which to cope; (2) relationships were strained at work; (3) clinical symptoms had repercussions on subjects' attitudes toward work and the relation to life outside of work; and (4) a variety of possible solutions were considered to help subjects better cope with fibromyalgia and work. CONCLUSIONS: Strategies that potentially could foster continued employment of patients with fibromyalgia include those at the micro, meso, and macro levels. Health care providers can support patients' employment goals by collaborating with patients and their employers, dispelling stigma regarding the illness, and providing practical and specific advice regarding workplace accommodations.

Contexte: Les douleurs chroniques, comme la fibromyalgie, affectent négativement la capacité des individus à travailler.Objectif: Le but de cette étude était d'examiner, du point de vue des patients, les effets des symptômes de la fibromyalgie sur leur capacité à travailler, les défis qu'ils ont rencontrés dans leur lieu de travail qui n'a pas favorisé leur maintien dans l'emploi, et les types de modifications à leur travail ou lieu de travail qui, selon eux, faciliteraient leur productivité et leur capacité à travailler.Méthodes: Une méthode d'examen de la portée, appliquant des techniques de revue systématique, a été utilisée pour effectuer une synthèse de la littérature concernant la fibromyalgie et le travail qui examinait ce problème du point de vue du patient.Résultats: Divers thèmes ont émergé de l'analyse et pourraient être globalement classés comme suit : (1) l'expérience de travail était difficile à gérer ; (2) les relations étaient tendues au travail ; (3) les symptômes cliniques ont eu des répercussions sur les attitudes des sujets envers le travail et leur rapport à la vie en dehors du travail ; et (4) diverses solutions possibles ont été envisagées pour aider les sujets à mieux faire face à la fibromyalgie au travail.Conclusions: Les stratégies susceptibles de favoriser l'emploi continu des patients atteints de fibromyalgie se situent aux niveaux micro, méso et macro. Les prestataires de soins de santé peuvent soutenir les objectifs d'emploi des patients en collaborant avec eux et leurs employeurs, afin de dissiper la stigmatisation qui entoure la maladie.

A multitarget basal ganglia dopaminergic and GABAergic transplantation strategy enhances behavioural recovery in parkinsonian rats.

The current transplantation paradigm for Parkinson's disease that places foetal dopaminergic cells in the striatum neither normalizes neuronal activity in basal ganglia structures such as the substantia nigra (SN) and subthalamic nucleus (STN) nor leads to complete functional recovery. It was hypothesized that restoration of parkinsonian deficits requires inhibition of the pathological overactivity of the STN and SN in addition to restoration of dopaminergic activity in the striatum. To achieve inhibition, a multitargeted basal ganglia transplantation strategy using GABAergic cells derived from either foetal striatal primordia (FSP) cells or human neural precursor cells (hNPCs) expanded in suspension bioreactors was investigated. In hemiparkinsonian rats, transplantation of foetal rat dopaminergic cells in the striatum in conjunction with GABAergic grafts in the STN and/or SN promoted significant improvement in forelimb akinesia and motor function compared to transplantation of intrastriatal dopaminergic grafts alone or in conjunction with undifferentiated hNPCs. In culture, FSP cells exhibited neuronal electrophysiological properties. However, recordings from GABAergic hNPCs revealed limited ionic conductances and an inability to fire action potentials. Despite this, they were almost as efficacious as FSP cells in inducing functional recovery following transplantation, suggesting that such recovery may have been mediated by secretion of GABA rather than by functional integration into the host. Thus, restoration of dopaminergic activity to the striatum in concert with inhibition of the STN and SN by GABAergic grafts may be beneficial for improving clinical outcomes in patients with Parkinson's disease and potential clinical application of this strategy may be enhanced by the use of differentiated hNPCs.

Adjunctive use of the non-ionic surfactant Poloxamer 188 improves fetal dopaminergic cell survival and reinnervation in a neural transplantation strategy for Parkinson's disease.

Although neural transplantation of fetal dopaminergic cells is a promising therapy for Parkinson's disease, poor transplanted cell survival limits its efficacy. In the present study it was hypothesized that the use of Poloxamer 188 (P188), a non-ionic surfactant, during cell preparation and transplantation may protect cells from associated mechanical injury and thus improve transplanted cell survival in a rat model of Parkinson's disease. Fetal rat dopaminergic tissue was dissociated in media with or without P188 and then cultured for 1 week or transplanted into the striatum of rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic pathway. Fetal dopaminergic cell survival and reinnervation of the host brain were examined using tyrosine hydroxylase immunohistochemistry and stereological quantification. The number of surviving tyrosine hydroxylase-immunoreactive cells in vitro and in vivo was significantly increased by 2.2-fold by incubating fetal dopaminergic cells with P188 during tissue dissociation. Furthermore, the striatal reinnervation in parkinsonian rats that received intrastriatal transplants of P188-exposed dopaminergic cells was significantly enhanced (1.8-fold increase) compared with rats that received non-P188-treated cells. In conclusion, P188 protects fetal dopaminergic cells from mechanical injury by increasing cell survival and enhances dopaminergic fibre outgrowth into the transplanted striatum. Use of P188 may thus be an important adjunct to improve the clinical efficacy of neural transplantation for Parkinson's disease.

Erythropoietin and GDNF enhance ventral mesencephalic fiber outgrowth and capillary proliferation following neural transplantation in a rodent model of Parkinson's disease.

Low dopaminergic cell survival and suboptimal fiber reinnervation are likely major contributing factors for the limited benefits of neural transplantation in Parkinson's disease (PD) patients. Glial cell lined-derived neurotrophic factor (GDNF) has been shown to enhance dopaminergic cell survival and fiber outgrowth of the graft site as well as promote behavioral recovery in rodent models of PD, while erythropoietin (EPO) can produce dopaminergic neuroprotective effects against 6-hydroxydopamine (6-OHDA) exposure on cultured neurons and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice. The aim of this study was to determine if fetal ventral mesencephalic (FVM) tissue exposed to hibernation media containing a combination of GDNF and EPO could enhance dopaminergic graft survival, striatal reinnervation and functional recovery in a 6-OHDA rodent model of PD. FVM tissue was dissected from 14-day-old rat fetuses and placed for 6 days in hibernation media alone, and in hibernation media that received either a daily administration of GDNF, EPO or a combination of GDNF and EPO. Following hibernation, FVM cells were transplanted as a single cell suspension into the striatum of unilateral 6-OHDA-lesioned rats. Rotational behavioral assessment revealed animals that received FVM tissue exposed to GDNF, EPO or the combination of both drugs had accelerated functional recovery. Immunohistochemical and stereological assessment revealed a significant increase in graft fiber density and angiogenesis into the graft when compared with control. These findings suggest that the hibernation of FVM tissue in a combination of GDNF and EPO can enhance graft efficacy and may have important implications for tissue preparation protocols for clinical neural transplantation in PD.

A novel role for parkin in trauma-induced central nervous system secondary injury.

Recently, loss-of-function mutations of parkin have been identified as being causally related to autosomal recessive juvenile parkinsonism, the most common form of familial Parkinson's disease. In addition to functioning as an E3 ubiquitin ligase that facilitates the proteasomal degradation of proteins with abnormal conformations, parkin protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. Parkin is expressed throughout the brain in a variety of functional and neurochemical systems. We propose that parkin's role in protecting neurons from oxidative stress may extend beyond the nigrostriatal system to include neurons in other regions of the central nervous system. This is relevant for therapeutic strategies for brain and spinal cord injury because oxidative stress leading to lipid peroxidation and protein and nucleic acid oxidation is a significant cause of secondary injury and thus neuronal death following traumatic injuries to the central nervous system. A novel model system to verify the process of oxidative stress as a causative factor in trauma-induced secondary injury mechanisms would be to induce traumatic brain and spinal cord injury in parkin-null mice. This is expected to provide the proof-of-principle that a cascade of oxidative stress is a causal event leading to secondary neuronal injury, that parkin functions outside of the dopaminergic system to protect other neurons from oxidative stress, and that antioxidant pharmacotherapy is a rational therapeutic approach to decrease trauma-induced neuronal injury.

A sequential intrastriatal dopaminergic graft strategy in the rodent model for Parkinson's disease: implications for graft survival and targeting.

Optimal placement of intrastriatal dopaminergic grafts is likely crucial to optimize clinical recovery in Parkinson's disease (PD). The target sites of dopaminergic grafts vary among clinical trials and may partially explain the variable results in clinical efficacy reported thus far. In this study we hypothesized that a subsequent dopaminergic graft may promote functional recovery following a suboptimal initial graft. To test this hypothesis, rats with unilateral 6-hydroxydopamine lesions of the right nigrostriatal pathway were randomly divided into three groups. The first group received 900,000 fetal nigral cells in the medial striatum only (n = 6). The second group received 900,000 cells in both the medial and lateral striatum simultaneously (1.8 million total; n = 8). The final group received a second graft of 900,000 cells in the lateral striatum 6 weeks following initial transplantation of a medial graft (n = 6). Amphetamine-induced circling behavior was significantly reduced in both simultaneous and sequential graft groups at 9 and 12 weeks following transplantation of the initial graft. However, no recovery was noted in the single medial graft group at those time points. Furthermore, increased survival of dopaminergic cells was observed in the lateral graft of sequentially grafted animals compared with the medial graft. We conclude that a well-positioned subsequent graft can restore function in animals with a suboptimal initial graft and that the initial graft may improve survival of the second graft. These results are further discussed in relation to their important clinical implication for neural transplantation in PD.

Enhancement of sensorimotor behavioral recovery in hemiparkinsonian rats with intrastriatal, intranigral, and intrasubthalamic nucleus dopaminergic transplants.

One of the critical variables that influences the efficacy of clinical neural transplantation for Parkinson's disease (PD) is optimal graft placement. The current transplantation paradigm that focuses on ectopic placement of fetal grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or normalize neuronal activity in important basal ganglia structures, such as the substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study was to investigate a multitarget neural transplantation strategy for PD by assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were randomly divided into eight groups and received lesions only or injections of 900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN, (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number of cells transplanted was equally divided among grafting sites. Animals with two grafts received 450,000 cells in each structure, and animals with three grafts received 300,000 cells per structure. Recovery was assessed by amphetamine-induced rotations and the stepping tests. Graft survival was assessed using tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation, simultaneous dopaminergic transplants in the ST, SN, and STN induced significant improvement in rotational behavior and stepping test scores. Intrastriatal transplants were associated with significant recovery of rotational asymmetry, whereas SN and STN transplants were associated with improved forelimb function scores. These results suggest that restoration of dopaminergic activity to multiple basal ganglia targets, such as the ST and SN, or the ST and STN, promotes a more complete functional recovery of complex sensorimotor behaviors. A multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of the basal ganglia may be crucial in improving clinical outcomes in PD patients.

The contributions of W.D. Stevenson to the development of neurosurgery in Atlantic Canada.

The establishment of a neurosurgical department in Halifax in January 1948 marked the beginnings of the first dedicated neurosurgical service in Atlantic Canada. The development of neurosurgery in Halifax occurred in a receptive place and time. The Victoria General Hospital, the region's largest tertiary care centre, and the Dalhousie University Faculty of Medicine were in a period of growth associated with medical specialization and departmentalization, changes inspired in part by the Flexner Report of 1910. Atlantic Canadians during this period were increasingly looking to specialists for their medical care. Although this social environment encouraged the establishment of surgical specialty services, the development of neurosurgery in Halifax, as in other parts of Canada, was closely associated with the efforts of individual neurosurgeons, such as William D. Stevenson. After training with Kenneth G. McKenzie in Toronto, Stevenson was recruited to Halifax and established the first neurosurgical department in Atlantic Canada. From the outset and over his twenty-six years as Department Head at the Victoria General Hospital and Dalhousie University, Stevenson worked to maintain the department's commitment to clinical practice, medical education, and research. Although Stevenson single-handedly ran the service for several years after its inception, by the time of his retirement in 1974 the neurosurgery department had grown to include five attending staff surgeons who performed over two thousand procedures each year. This paper highlights the importance of Stevenson's contributions to the development of neurosurgery in Atlantic Canada within the context of the social and medical environment of the region.