Exploring the Role of Negative Cognitions in the Relationship Between Ethnicity, Sleep, and Pain in Women With Temporomandibular Joint Disorder.

Negative cognitions are central to the perpetuation of chronic pain and sleep disturbances. Patients with temporomandibular joint disorder (TMJD), a chronic pain condition characterized by pain and limitation in the jaw area, have a high comorbidity of sleep disturbances that possibly exacerbate their condition. Ethnic group differences are documented in pain, sleep, and coping, yet the mechanisms driving these differences are still unclear, especially in clinical pain populations. We recruited 156 women (79% white, 21% African American) diagnosed with TMJD as part of a randomized, controlled trial evaluating the effectiveness of interventions targeting sleep and pain catastrophizing on pain in TMJD. Analysis of baseline data demonstrated that, relative to white participants, African Americans exhibited higher levels of clinical pain, insomnia severity, and pain catastrophizing, yet there was no ethnic group difference in negative sleep-related cognitions. Mediation models revealed pain catastrophizing, but not sleep-related cognitions or insomnia severity, to be a significant single mediator of the relationship between ethnicity and clinical pain. Only the helplessness component of catastrophizing together with insomnia severity sequentially mediated the ethnicity-pain relationship. These findings identify pain catastrophizing as a potentially important link between ethnicity and clinical pain and suggest that interventions targeting pain-related helplessness could improve both sleep and pain, especially for African American patients. Perspective:Pain-related helplessness and insomnia severity contribute to ethnic differences found in clinical pain among woman with TMJD. Findings can potentially inform interventions that target insomnia and catastrophizing to assist in reducing ethnic disparities in clinical pain.

Impact of a person-centred community rehabilitation service on outcomes for individuals with a neurological condition.

PURPOSE: To evaluate the impact of a person-centred, community rehabilitation service on outcomes for people with a neurological condition, in the first year of service. METHOD: A prospective, observational, pre-post study was conducted with 206 people who had a neurological condition and attended the rehabilitation service to restore function (e.g., Stroke); maximize recovery in an ongoing situation (e.g., Spina Bifida); or maximize function and independence while preparing for inevitable decline (e.g., Parkinson's Disease). Outcomes were measured via self-report questionnaires, prior to, and following three months of rehabilitation. The primary outcome was achievement of self-identified goals, measured by the Patient-Specific Functional scale. Secondary outcomes included the Lawton Instrumental Activities of Daily Living (IADL) scale, EQ-5D-5L European Quality of Life scale, and ICECAP-O - Index of Capability for Older Adults and health and medical resource use. RESULTS: Participants demonstrated significant goal achievement and a significant reduction in health and medical resource use. There were small positive changes in the Lawton IADL, EQ-5D-5L, and ICECAP-O however these changes were not significant. CONCLUSIONS: In the first year of operation, the community rehabilitation service made a significant impact on outcomes for individuals with a neurological condition. Further research is required to identify appropriate measures of activities of daily living and quality of life that reflect person-centred rehabilitation outcomes for restoring function, maximizing function, or preparing for functional decline. Implications for Rehabilitation Self-identified goals are an important guide for achievement of meaningful outcomes for individuals with a neurological condition. Person-centred outcome measures are required to evaluate the benefits of a person-centred community rehabilitation service for individuals with a neurological condition.

Measuring nerve regeneration in the mouse.

Genetic engineering of mice has become a major tool in understanding the roles of individual molecules in regeneration of nerves, and will play an increasing role in the future. Mice are in many ways well suited to assessment both of nerve regeneration after axotomy and of collateral sprouting of intact fibers into areas of denervation. However, mouse models present special challenges because of their small size, their inherent capacity for regeneration, and the potential strain effects. The most widely used model of regeneration, sciatic nerve injury, has its inherent limitations, and there is a need for other models of injury to long nerves. Measures of regeneration in the mouse can be divided into those that assess the latency to initiate growth, those sensitive to the rate of growth and the proportion of fibers growing at fast rates, those that assess the time to reinnervation of specific targets and the completeness of reinnervation, and those that assess specificity of reinnervation and functional recovery. The short length of nerve available in the mouse limits measures of the rates of outgrowth, and thus introduces a greater potential for "noise" of measurement than is seen in larger animals such as the rat. For both regeneration of interrupted fibers and collateral regeneration from intact fibers histological and physiological measures of "time to target" have the advantages of direct correlation with restoration of function, the ability to assess regeneration of different fiber types efficiently, and the fact that most of these measures are easier in the mouse than in the rat.

Impaired synaptic vesicle release and immaturity of neuromuscular junctions in spinal muscular atrophy mice.

The motor neuron disease spinal muscular atrophy (SMA) causes profound muscle weakness that most often leads to early death. At autopsy, SMA is characterized by loss of motor neurons and muscle atrophy, but the initial cellular events that precipitate motor unit dysfunction and loss remain poorly characterized. Here, we examined the function and corresponding structure of neuromuscular junction (NMJ) synapses in a mouse model of severe SMA (hSMN2/delta7SMN/mSmn-/-). Surprisingly, most SMA NMJs remained innervated even late in the disease course; however they showed abnormal synaptic transmission. There was a two-fold reduction in the amplitudes of the evoked endplate currents (EPCs), but normal spontaneous miniature EPC (MEPC) amplitudes. These features in combination indicate reduced quantal content. SMA NMJs also demonstrated increased facilitation suggesting a reduced probability of vesicle release. By electron microscopy, we found a decreased density of synaptic vesicles that is likely to contribute to the reduced release probability. In addition to presynaptic defects, there were postsynaptic abnormalities. EPC and MEPC decay time constants were prolonged because of a slowed switch from the fetal acetylcholine receptor (AChR) gamma-subunit to the adult epsilon-subunit. There was also reduced size of AChR clusters and small myofibers, which expressed an immature pattern of myosin heavy chains. Together these results indicate that impaired synaptic vesicle release at NMJs in severe SMA is likely to contribute to failed postnatal maturation of motor units and muscle weakness.

A novel endogenous erythropoietin mediated pathway prevents axonal degeneration.

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.

Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons.

Human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HIV-SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor-alpha and subsequent TNFR1-mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell-neuron interaction may be pathogenically relevant not only in HIV-SN but also in other peripheral neuropathies.