Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

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Abstract

Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

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Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera.

Lars Arendt-Nielsen, David Yarnitsky (2009)

Quantification of the human painful sensory experience is an essential step in the translation of knowledge from animal nociception to human pain. Translational models for assessment of pain are very important, as such models can be used in: 1) basic mechanistic studies in healthy volunteers; 2) clinical studies for diagnostic and monitoring purposes; 3) pharmacological studies to evaluate analgesic efficacy of new and existing compounds. Quantitative pain assessment, or quantitative sensory testing (QST), provides psychophysical methods that systematically document alterations and reorganization in nervous system function and, in particular, the nociceptive system. QST is defined as the determination of thresholds or stimulus response curves for sensory processing under normal and pathophysiological conditions. The modern concept of advanced QST for experimental pain assessment is a multimodality, multitissue approach where different pain modalities (thermal, mechanical, electrical, and chemical) are applied to different tissues (skin, muscles, and viscera) and the responses are assessed by psychophysical methods (thresholds and stimulus-response functions). Many new and advanced technologies have been developed to help relieve evoked, standardized, and painful reactions. Assessing pain has become a question of solving a multi-input, multi-output problem, with the solution providing the possibility of teasing out which pain pathways and mechanisms are involved, impaired, or affected. Many methodologies have been developed for quantitative assessment of pain perception and involved mechanisms. This paper describes the background for the different methods, the use in basic pain experiments on healthy volunteers, how they can be applied in drug profiling, and the applications in clinical practice.

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The impact of chronic pain in the community.

B Smith, A. M. Elliott, W A Chambers … (2001)

Chronic pain is known to be very common in the community. Less is known about the epidemiology of more significant or severe chronic pain. The impact of chronic pain in the community, in terms of general health, employment and interference with daily activity, has not been quantified. The aim of this study was to describe the prevalence and distribution in the community of chronic pain defined as 'significant' and 'severe', and to explore the impact of chronic pain on health and activity. A questionnaire survey was carried out of a sample drawn from the general population in the Grampian region of SCOTLAND: Questionnaires were sent to a random sample of 4611 individuals aged 25 years and over, stratified for age and gender, selected from the practice lists of 29 general practices (total practice population 136,383). The study instrument included a case definition questionnaire, from which were identified individuals with 'any chronic pain' (pain of at least 3 months duration). The instrument also included a level of expressed need questionnaire and the chronic pain grade questionnaire, from which were derived definitions for 'significant chronic pain' (based on the reported need for treatment and professional advice) and 'severe chronic pain' (based on reported intensity and pain-related disability). The SF-36 general health questionnaire and demographic questions were also included. Of the sample, 14.1% reported 'significant chronic pain', and this was more prevalent among women and older age groups. A total of 6.3% reported 'severe chronic pain', and this was more common in older age groups. On multiple logistic regression modelling, female gender, housing tenure, employment category and educational attainment were found to be independently associated with both 'significant' and 'severe' chronic pain. The presence of 'any', 'significant' and 'severe' chronic pain had progressively more marked adverse associations with employment, interference with daily activities and all measured dimensions of general health. Comparison of the epidemiology of 'significant chronic pain' and 'severe chronic pain' with 'any chronic pain' allows an understanding of the more clinically important end of the chronic pain spectrum. These results support the suggestion that chronic pain is multidimensional, both in its aetiology and in its effects, particularly at this end of the spectrum. This must be addressed in management and in further research.