Herpes Simplex Virus Infection, Pathological Pain and Recurrent Lymphocytic Meningitis

Background: Aims of the study were: (i) to characterise the clinical picture, immunological features and changes in brain morphology and function in patients with widespread unilateral pain and HSV-infections, and (ii) to analyse the prevalence, clinical symptoms and immunological predisposing factors of HSV-2 induced recurrent lymphocytic meningitis (RLM) in Southern Finland. Patients and methods: Patients for the studies were recruited from the Pain Clinic, and from the Department of Neurology, at Helsinki University Central Hospital. Plasma concentrations of IgM, IgA, IgG, and IgG1-4, and serum concentrations of C3, C4 were measured. Serological anti-HSV-1 and -2 antibody status was tested. C4 genotyping, HLA-A, HLA-B and HLA-DRB1 typing, MBL2 genotyping, and IgG1 and IgG3 allotyping (Gm) were performed. Clinical neurological examination, quantitative sensory testing, skin biopsy, and functional magnetic resonance imaging were also performed. Results: HSV probably has a role in the generation of a pathological pain state. Low serum IgG1 and IgG3 levels, made the patients vulnerable for recurring HSV infections. Both functional and structural changes were observed in the brain pain-processing areas in the patients: they had less pain-related activity in the insular cortices bilaterally, in the anterior cingular cortex (ACC), and in the thalamus, and the gray matter density was lower in the ACC, in the frontal and prefrontal cortices. In the meningitis studies it was shown that RLM is more common and less benign than previously reported, and that neuropathic pain is frequently present both during and after meningitis episodes. HLA-DRB1*01, HLA-B*27, and low IgG1 levels are predisposing factors for RLM. Conclusions: Patients are vulnerable to recurrent HSV infections because of subtle immunological abnormalities. HSV causes diverse clinical manifestations. First, the herpes simplex virus, or the inflammatory process triggered by it, may cause pathological widespread pain probably by activating glial cells in the CNS. In these patients, signs of alterations in the brain pain-processing areas can be demonstrated by functional brain imaging methods. Secondly, HSV-2 induced RLM is a rare complication of HSV-2 virus. The predisposing factors include low IgG1 subclass levels, HLA-DRB1*01 and HLA –B*27 genotypes. Neuropathic pain is frequently associated with RLM.

Brain imaging of chronic pain

Acute pain has substantial survival value because of its protective function in the everyday environment. Instead, chronic pain lacks survival and adaptive function, causes great amount of individual suffering, and consumes the resources of the society due to the treatment costs and loss of production. The treatment of chronic pain has remained challenging because of inadequate understanding of mechanisms working at different levels of the nervous system in the development, modulation, and maintenance of chronic pain. Especially in unclear chronic pain conditions the treatment may be suboptimal because it can not be targeted to the underlying mechanisms. Noninvasive neuroimaging techniques have greatly contributed to our understanding of brain activity associated with pain in healthy individuals. Many previous studies, focusing on brain activations to acute experimental pain in healthy individuals, have consistently demonstrated a widely-distributed network of brain regions that participate in the processing of acute pain. The aim of the present thesis was to employ non-invasive brain imaging to better understand the brain mechanisms in patients suffering from chronic pain. In Study I, we used magnetoencephalography (MEG) to measure cortical responses to painful laser stimulation in healthy individuals for optimization of the stimulus parameters for patient studies. In Studies II and III, we monitored with MEG the cortical processing of touch and acute pain in patients with complex regional pain syndrome (CRPS). We found persisting plastic changes in the hand representation area of the primary somatosensory (SI) cortex, suggesting that chronic pain causes cortical reorganization. Responses in the posterior parietal cortex to both tactile and painful laser stimulation were attenuated, which could be associated with neglect-like symptoms of the patients. The primary motor cortex reactivity to acute pain was reduced in patients who had stronger spontaneous pain and weaker grip strength in the painful hand. The tight coupling between spontaneous pain and motor dysfunction supports the idea that motor rehabilitation is important in CRPS. In Studies IV and V we used MEG and functional magnetic resonance imaging (fMRI) to investigate the central processing of touch and acute pain in patients who suffered from recurrent herpes simplex virus infections and from chronic widespread pain in one side of the body. With MEG, we found plastic changes in the SI cortex, suggesting that many different types of chronic pain may be associated with similar cortical reorganization. With fMRI, we found functional and morphological changes in the central pain circuitry, as an indication of central contribution for the pain. These results show that chronic pain is associated with morphological and functional changes in the brain, and that such changes can be measured with functional imaging.

Older male and female drivers in car-dependent settings: How much do they use other modes, and do they compensate for reduced driving to maintain mobility?

Among the societal and health challenges of population ageing is the continued transport mobility of older people who retain their driving licence, especially in highly car-dependent societies. While issues surrounding loss of a driving licence have been researched, less attention has been paid to variations in physical travel by mode among the growing proportion of older people who retain their driving licence. It is unclear how much they reduce their driving with age, the degree to which they replace driving with other modes of transport, and how this varies by age and gender. This paper reports research conducted in the state of Queensland, Australia, with a sample of 295 older drivers (>60 years). Time spent driving is considerably greater than time spent as a passenger or walking across age groups and genders. A decline in travel time as a driver with increasing age is not redressed by increases in travel as a passenger or pedestrian. The patterns differ by gender, most likely reflecting demographic and social factors. Given the expected considerable increase in the number of older women in particular, and their reported preference not to drive alone, there are implications for policies and programmes that are relevant to other car-dependent settings. There are also implications for the health of older drivers, since levels of walking are comparatively low.

“Well this is it. Just get on with it”: Pain willingness and activity engagement in people with chronic pain

Pain is recognised as a problem of significant concern worldwide and in the latest Global Burden of Disease Study, low back pain was identified as the biggest contributor worldwide to Years Lived with Disability. There is evidence to suggest that people who accept their chronic pain have a higher quality of life, lower levels of disability and distress, and function better emotionally, socially and physically. Findings on the specific pathways linking pain acceptance to quality of life outcomes are less clear. the two widely accepted pain acceptance factors, pain willingness and activity engagement, have not been well explored in qualitative studies on acceptance of chronic pain. To address this deficit in the literature, the current study has two related aims: 1) to explore pain willingness and activity engagement in the lives of people with chronic pain, and ; 2) to find out what people believe helps them to successfully get on with life in spite of chronic pain.

'Ladd traps' as a visual trap for male and female Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae)

Bactrocera tryoni (Froggatt) is Australia's major horticultural insect pest, yet monitoring females remains logistically difficult. We trialled the ‘Ladd trap’ as a potential female surveillance or monitoring tool. This trap design is used to trap and monitor fruit flies in countries other (e.g. USA) than Australia. The Ladd trap consists of a flat yellow panel (a traditional ‘sticky trap’), with a three dimensional red sphere (= a fruit mimic) attached in the middle. We confirmed, in field-cage trials, that the combination of yellow panel and red sphere was more attractive to B. tryoni than the two components in isolation. In a second set of field-cage trials, we showed that it was the red-yellow contrast, rather than the three dimensional effect, which was responsible for the trap's effectiveness, with B. tryoni equally attracted to a Ladd trap as to a two-dimensional yellow panel with a circular red centre. The sex ratio of catches was approximately even in the field-cage trials. In field trials, we tested the traditional red-sphere Ladd trap against traps for which the sphere was painted blue, black or yellow. The colour of sphere did not significantly influence trap efficiency in these trials, despite the fact the yellow-panel/yellow-sphere presented no colour contrast to the flies. In 6 weeks of field trials, over 1500 flies were caught, almost exactly two-thirds of them being females. Overall, flies were more likely to be caught on the yellow panel than the sphere; but, for the commercial Ladd trap, proportionally more females were caught on the red sphere versus the yellow panel than would be predicted based on relative surface area of each component, a result also seen the field-cage trial. We determined that no modification of the trap was more effective than the commercially available Ladd trap and so consider that product suitable for more extensive field testing as a B. tryoni research and monitoring tool.

Investigating the effect of Eye Movement Desensitization and Reprocessing (EMDR) on postoperative pain intensity in adolescents undergoing surgery: A randomized controlled trial

Aim To investigate the efficacy of Eye Movement Desensitization and Reprocessing for postoperative pain management in adolescents. Background Eye Movement Desensitization and Reprocessing is an inexpensive, non-pharmacological intervention that has successfully been used to treat chronic pain. It holds promise in the treatment of acute, postsurgical pain based on its purported effects on the brain and nervous system. Design A randomized controlled trial was used. Methods Fifty-six adolescent surgical patients aged between 12-18 years were allocated to gender-balanced Eye Movement Desensitization and Reprocessing (treatment) or non-Eye Movement Desensitization and Reprocessing (control) groups. Pain was measured using the Wong-Baker FACES® Pain Rating Scale (WBFS) before and after the intervention (or non-intervention for the control group). Findings A Wilcoxon signed-rank test demonstrated that the Eye Movement Desensitization and Reprocessing group experienced a significant reduction in pain intensity after treatment intervention, whereas the control group did not. Additionally, a Mann–Whitney U-test showed that, while there was no significant difference between the two groups at time 1, there was a significant difference in pain intensity between the two groups at time 2, with the Eye Movement Desensitization and Reprocessing group experiencing lower levels of pain. Conclusion These results suggest that Eye Movement Desensitization and Reprocessing may be an effective treatment modality for postoperative pain.

Management of persistent pain in the older people

Persistent pain is a commonly experienced symptom. It affects 25% of community-dwelling older adults and up to 80% of nursing home residents, and can have a major impact on quality of life and functional capacity. Unfortunately pain in older patients is often undertreated and misunderstood. Assessment of pain type and severity is important. Most older people, even with moderately impaired cognition, are able to self-report pain. Validated assessment tools using non-verbal pain cues are available for people with more advanced cognitive impairment. Management of pain in older people can be challenging. Physiological changes may impact on pain perception and the pharmacodynamics and pharmacokinetics of medications. Older people are often more sensitive to the adverse effects of analgesic medications and are at risk of drug–drug interactions due to the presence of co-morbidities and polypharmacy. In general, analgesic medications should be commenced at low doses, titrated based on effect and tolerability, and regularly reviewed. Contemporary pain management often utilises multiple analgesics in lower doses to optimise efficacy and avoid dose-related toxicity. A bio-psycho-social approach to the management of persistent pain, utilising a multidisciplinary team and including non-drug strategies, may produce the best results. The goal of pain management is not always to eliminate pain, since this may not be attainable, but rather to enhance function and improve quality of life. This article discusses persistent non-cancer pain in older people, its assessment and management, and the risks and benefits of pharmacological treatment in this population.

Gender and female entrepreneurship in a pro-entrepreneurship magazine

In this working paper I discuss gendered entrepreneurship by exploring how the media writes about female entrepreneurship. The starting point is that the media when talking and writing about female entrepreneurs and female entrepreneurship, mould meanings of gender in entrepreneurship. I view entrepreneurship and gender as socially constructed, discursive phenomena. To uncover the processes of constructing gender in female entrepreneurship this paper applies a discursive framework, which treats language as a representational system producing and circulating meaning. The focus on language use as action implies that practises of writing and talking about female entrepreneurship ‘make’ gender as much as the women entrepreneurs) themselves: both involve working on culturally shared meanings to make reality intelligible. The data consists of articles published in Yrittäjä, a pro-SME magazine, in 1990-1997. In the analysis I show how gender is constructed in media talk. as a women’s issue Women entrepreneurs are constantly compared with men and with an implicitly masculine ideal of entrepreneurship and with strengths and weaknesses of women are displayed pointing out that the meaning making of gender taking place in the data refers to equality discourse. Finally I discuss possible consequences of the hegemonic equality discourse and suggest lines of further research.

Male spacing behaviour and acoustic interactions in a field cricket: implications for female mate choice

Males of several acoustically communicating orthopteran species form spatially and temporally structured choruses. We investigated whether male field crickets of the species Plebeiogryllus guttiventris formed choruses in the field. Males formed spatial aggregations and showed fidelity to a calling site within a night, forming stable choruses. Within aggregations, the acoustic ranges of males overlapped considerably. We tested whether males within hearing range of each other interacted acoustically. The chirps of simultaneously calling males were aphasic with respect to each other and showed no significant alternation or synchrony of calls. Some individuals changed temporal features of their calling songs such as chirp durations and chirp rates in response to a simultaneously calling neighbour. The implications of these results for female mate choice are discussed