Chronic pain associated with the Chikungunya Fever: long lasting burden of an acute illness

Abstract Background Chikungunya virus (CHIKV) is responsible for major epidemics worldwide. Autochthonous cases were recently reported in several European countries. Acute infection is thought to be monophasic. However reports on chronic pain related to CHIKV infection have been made. In particular, the fact that many of these patients do not respond well to usual analgesics suggests that the nature of chronic pain may be not only nociceptive but also neuropathic. Neuropathic pain syndromes require specific treatment and the identification of neuropathic characteristics (NC) in a pain syndrome is a major step towards pain control. Methods We carried out a cross-sectional study at the end of the major two-wave outbreak lasting 17 months in Réunion Island. We assessed pain in 106 patients seeking general practitioners with confirmed infection with the CHIK virus, and evaluated its impact on quality of life (QoL). Results The mean intensity of pain on the visual-analogical scale (VAS) was 5.8 ± 2.1, and its mean duration was 89 ± 2 days. Fifty-six patients fulfilled the definition of chronic pain. Pain had NC in 18.9% according to the DN4 questionnaire. Conversely, about two thirds (65%) of patients with NC had chronic pain. The average pain intensity was similar between patients with or without NC (6.0 ± 1.7 vs 6.1 ± 2.0). However, the total score of the Short Form-McGill Pain Questionnaire (SF-MPQ)(15.5 ± 5.2 vs 11.6 ± 5.2; p < 0.01) and both the affective (18.8 ± 6.2 vs 13.4 ± 6.7; p < 0.01) and sensory subscores (34.3 ± 10.7 vs 25.0 ± 9.9; p < 0.01) were significantly higher in patients with NC. The mean pain interference in life activities calculated from the Brief Pain Inventory (BPI) was significantly higher in patients with chronic pain than in patients without it (6.8 ± 1.9 vs 5.9 ± 1.9, p < 0.05). This score was also significantly higher in patients with NC than in those without such a feature (7.2 ± 1.5 vs 6.1 ± 1.9, p < 0.05). Conclusions There exists a specific chronic pain condition associated to CHIKV. Pain with NC seems to be associated with more aggressive clinical picture, more intense impact in QoL and more challenging pharmacological treatment.

Influence of myofascial pain on the pressure pain threshold of masticatory muscles in women with migraine

Objective: To evaluate the influence of myofascial pain on the Pressure Pain Threshold (PPT) of masticatory muscles in women with migraine. Methods: The sample comprised 101 women, ages ranging from 18 to 60 years, with an episodic migraine diagnosis previously confirmed by a neurologist. All patients were evaluated using Research Diagnostic Criteria for Temporomandibular Disorders to determine the presence of myofascial pain and were divided into 2 groups: group I (n=56), comprising women with a migraine, and group II (n=45), comprising women with a migraine and myofascial pain. Two more groups (49 asymptomatic women and 50 women with myofascial pain), matched for sex and race, obtained from a previous study, were added to this study. The PPT values of masseter and temporalis (anterior, middle, and posterior regions) muscles were recorded bilaterally using a pressure algometer. One-way analysis of variance and the Tukey test for pairwise comparisons were used in statistical analysis with a 5% significance level. Results: We found that all groups had significantly lower PPT values compared with asymptomatic women, with lower values seen in group II (women with migraine and myofascial pain). Women with a migraine and myofascial pain showed significantly lower PPT values compared with women with a migraine only, and also when compared with women with myofascial pain only. Discussion: Migraine, especially when accompanied by myofascial pain, reduces the PPT of masticatory muscles, suggesting the importance of masticatory muscle palpation during examination of patients with migraine.

Psychometric validation of the Portuguese version of the Neuropathic Pain Symptoms Inventory

Backgroud: It has been shown that different symptoms or symptom combinations of neuropathic pain (NeP) may correspond to different mechanistic backgrounds and respond differently to treatment. The Neuropathic Pain Symptom Inventory (NPSI) is able to detect distinct clusters of symptoms (i.e. dimensions) with a putative common mechanistic background. The present study described the psychometric validation of the Portuguese version (PV) of the NPSI. Methods: Patients were seen in two consecutive visits, three to four weeks apart. They were asked to: (i) rate their mean pain intensity in the last 24 hours on an 11-point (0-10) numerical scale; (ii) complete the PV-NPSI; (iii) provide the list of pain medications and doses currently in use. VAS and Global Impression of Change (GIC) were filled out in the second visit. Results: PV-NPSI underwent test-retest reliability, factor analysis, analysis of sensitivity to changes between both visits. The PV-NPSI was reliable in this setting, with a good intra-class correlation for all items. The factorial analysis showed that the PV-NPSI inventory assessed different components of neuropathic pain. Five different factors were found. The PV-NPSI was adequate to evaluate patients with neuropathic pain and to detect clusters of NeP symptoms. Conclusions: The psychometric properties of the PV-NPSI rendered it adequate to evaluate patients with both central and peripheral neuropathic pain syndromes and to detect clusters of NeP symptoms.

Pain and quality of life in patients undergoing radiotherapy for spinal metastatic disease treatment

Abstract Background Radiotherapy is an important tool in the control of pain in patients with spinal metastatic disease. We aimed to evaluate pain and of quality of life of patients with spinal metastatic disease undergoing radiotherapy with supportive treatment. Methods The study enrolled 30 patients. From January 2008 to January 2010, patients selection included those treated with a 20 Gy tumour dose in five fractions. Patients completed the visual analogue scale for pain assessment and the SF-36 questionnaire for quality of life assessment. Results The most frequent primary sites were breast, multiple myeloma, prostate and lymphoma. It was found that 14 spinal metastatic disease patients (46.66%) had restricted involvement of three or fewer vertebrae, while 16 patients (53.33%) had cases involving more than three vertebrae. The data from the visual analogue scale evaluation of pain showed that the average initial score was 5.7 points, the value 30 days after the end of radiotherapy was 4.60 points and the average value 6 months after treatment was 4.25 points. Notably, this final value was 25.43% lower than the value from the initial analysis. With regard to the quality of life evaluation, only the values for the functional capability and social aspects categories of the questionnaire showed significant improvement. Conclusion Radiotherapy with supportive treatment appears to be an important tool for the treatment of pain in patients with spinal metastatic disease.

Pain in preterm infants: effects of sex, gestational age, and neonatal illness severity

Neonates hospitalized in a neonatal intensive care unit are exposed to many painful and stressful procedures. Biobehavioral pain reactivity in preterm infants during the neonatal period may reflect the capacity of the central nervous system to regulate arousal and neurobiological organization. We review empirical studies on the effects of sex, gestational age, and neonatal illness severity on pain reactivity in children born preterm. A literature search was conducted using PubMed, Institute of Scientific Information Web of Science, PsycINFO, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online databases. Additionally, a special search was performed in online journals that publish pain studies including Pain, Early Human Development, European Journal of Pain, and Pain Management Nursing. The literature search covered the period from 2004 to 2009. Data were extracted according to predefined inclusion and exclusion criteria. Of the 18 studies reviewed, 16 analyzed gestational age, 13 examined neonatal illness severity, and eight focused on sex. Most of the studies analyzed more than one of these three variables. The majority of the studies found effects of gestational age (n = 14) and neonatal illness severity (n = 11) on pain responses. Only two studies found an influence of sex on infant pain responses. In conclusion, gestational age and neonatal illness severity influence pain responses in infants born preterm. Further studies should be conducted to examine the influence of sex on pain responses.

Laser therapy and pain-related behavior after injury of the inferior alveolar nerve: possible involvement of neurotrophins

Nerve-related complications have been frequently reported in dental procedures, and a very frequent type of occurrence involves the inferior alveolar nerve (IAN). The nerve injury in humans often results in persistent pain accompanied by allodynia and hyperalgesia. In this investigation, we used an experimental IAN injury in rats, which was induced by a Crile hemostatic clamp, to evaluate the effects of laser therapy on nerve repair. We also studied the nociceptive behavior (von Frey hair test) before and after the injury and the behavioral effects of treatment with laser therapy (emitting a wavelength of 904 nm, output power of 70 Wpk, a spot area of *0.1 cm2, frequency of 9500 Hz, pulse time 60 ns and an energy density of 6 J/cm2). As neurotrophins are essential for the process of nerve regeneration, we used immunoblotting techniques to preliminarily examine the effects of laser therapy on the expression of nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF). The injured animals treated with laser exhibited an improved nociceptive behavior. In irradiated animals, there was an enhanced expression of NGF (53%) and a decreased BDNF expression (40%) after laser therapy. These results indicate that BDNF plays a locally crucial role in pain-related behavior development after IAN injury, increasing after lesions (in parallel to the installation of pain behavior) and decreasing with laser therapy (in parallel to the improvement of pain behavior). On the other hand, NGF probably contributes to the repair of nerve tissue, in addition to improving the pain-related behavior.

Reference values of mechanical and thermal pain tests in a pain-free population

Quantitative sensory tests are widely used in human research to evaluate the effect of analgesics and explore altered pain mechanisms, such as central sensitization. In order to apply these tests in clinical practice, knowledge of reference values is essential. The aim of this study was to determine the reference values of pain thresholds for mechanical and thermal stimuli, as well as withdrawal time for the cold pressor test in 300 pain-free subjects. Pain detection and pain tolerance thresholds to pressure, heat and cold were determined at three body sites: (1) lower back, (2) suprascapular region and (3) second toe (for pressure) or the lateral aspect of the leg (for heat and cold). The influences of gender, age, height, weight, body-mass index (BMI), body side of testing, depression, anxiety, catastrophizing and parameters of Short-Form 36 (SF-36) were analyzed by multiple regressions. Quantile regressions were performed to define the 5th, 10th and 25th percentiles as reference values for pain hypersensitivity and the 75th, 90th and 95th percentiles as reference values for pain hyposensitivity. Gender, age and/or the interaction of age with gender were the only variables that consistently affected the pain measures. Women were more pain sensitive than men. However, the influence of gender decreased with increasing age. In conclusion, normative values of parameters related to pressure, heat and cold pain stimuli were determined. Reference values have to be stratified by body region, gender and age. The determination of these reference values will now allow the clinical application of the tests for detecting abnormal pain reactions in individual patients.

The role of central hypersensitivity in the determination of intradiscal mechanical hyperalgesia in discogenic pain

OBJECTIVE: The primary aim of the present study was to investigate whether there is a relationship between central hypersensitivity (assessed by pressure pain thresholds of uninjured tissues) and intradiscal pain threshold during discography. The secondary aim was to test the hypothesis that peripheral noxious stimulation dynamically modulates central hypersensitivity. PATIENTS: Twenty-four patients with positive provocation discography were tested for central hypersensitivity by pressure algometry before and after the intervention with assessments of pressure pain detection and tolerance thresholds. Intradiscal pain threshold was assessed by measuring intradiscal pressure at the moment of pain provocation during discography. Correlation analyses between intradiscal pain threshold and pressure algometry were made. For the secondary aim, pressure algometry data before and after discography were compared. RESULTS: Significant correlation with intradiscal pain threshold was found for pressure pain detection threshold at the toe (regression coefficient: 0.03, P = 0.05) and pressure pain tolerance thresholds at the nonpainful point at the back (0.02, P = 0.024). Tolerance threshold at the toe was a significant predictor for intradiscal pain threshold only in multiple linear regression (0.036, P = 0.027). Detection as well as tolerance thresholds significantly decreased after discography at the painful and the nonpainful point at the back, but not at the toe. CONCLUSIONS: Central hypersensitivity may influence intradiscal pain threshold, but with a modest quantitative impact. The diagnostic value of provocation discography is therefore not substantially impaired. Regional, but not generalized central hypersensitivity is dynamically modulated by ongoing peripheral nociceptive input.

The course of chronic and recurrent low back pain in the general population

Using latent class analysis (LCA), a previous study on patients attending primary care identified four courses of low back pain (LBP) over the subsequent 6 months. To date, no studies have used longitudinal pain recordings to examine the "natural" course of recurrent and chronic LBP in a population-based sample of individuals. This study examines the course of LBP in the general population and elaborates on the stability and criterion-related validity of the clusters derived. A random sample of 400 individuals reporting LBP in a population-based study was asked to complete a comprehensive questionnaire at the start and end of the year's survey, and 52 weekly pain diaries in between. The latter were analyzed using LCA. 305 individuals returned more than 50% of the diaries. Four clusters were identified (severe persistent, moderate persistent, mild persistent, and fluctuating). The clusters differed significantly with regards to pain and disability. Assessment of cluster stability showed that a considerable proportion of patients in the "fluctuating" group changed their classification over time. Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care. Due to the population-based design, this study achieves, for the first time, a close insight into the "natural" course of chronic and recurrent low back pain, including individuals that did not necessarily visit the general practitioner. The findings will help to understand better the nature of this pain in the general population.

Association of bone attrition with knee pain, stiffness and disability: a cross-sectional study

Bone pathologies as detected on MRI are associated with the presence of pain in knee osteoarthritis (OA). The authors examined whether bone attrition assessed on x-rays was associated with pain, stiffness and disability.

[Characteristics of patients suffering from chronic pain with depressive symptoms in three different treatment settings]

Only few studies considered demographic and medical characteristics of pain patients with depressive symptoms.

[Pathophysiology of abdominal pain]

Abdominal pain can be induced by stimulation of visceral nociceptors. Activation of nociceptors usually requires previous sensitization by pathological events, such as inflammation, ischemia or acidosis. Although abdominal pain can obviously be caused by pathology of a visceral structure, clinicians frequently observe that such a pathology explains only part of the pain complaints. Occasionally, there is lack of objective signs of visceral lesions. There is clear evidence that pain states are associated with profound changes of the central processing of the sensory input. The main consequences of such alterations for patients are twofold: 1) a central sensitization, i.e. an increased excitability of the central nervous system; 2) an alteration of the endogenous pain modulation, which under normal conditions inhibits the processing of nociceptive signals in the central nervous system. Both phenomena lead to a spread of pain to other body regions and an amplification of the pain perception. The interactions between visceral pathology and alterations of the central pain processes represent an at least partial explanation for the discrepancy between objective signs of peripheral lesions and severity of the symptoms. Today, both central hypersensitivity and alteration in endogenous pain modulation can be measured in clinical practice. This information can be used to provide the patients with an explanatory model for their pain. Furthermore, first data suggest that alterations in central pain processing may represent negative prognostic factors. A better understanding of the individual pathophysiology may allow in the future the development of individual therapeutic strategies.

Factors determining the success of radiofrequency denervation in lumbar facet joint pain: a prospective study

Background and aims Radiofrequency denervation (RF) of the lumbar facet joints has been shown to be effective in well-selected patients. However, long-term success varies between studies. We evaluated the influence of selected psychosocial and constitutional factors on the outcome of RF, expressed as the duration of pain relief. Methods This prospective observational study included 44 patients who received RF denervations at the University Hospital of Berne. Success was defined as at least 50% pain reduction 7–21 days, 6 months and 1 year after RF therapy. The Cox-regression analysis was performed to evaluate the influence of the following factors on the duration of success: age, sex, depression, work inability and previous surgery. Results Complete follow-up was available for 41 patients. The success rate 7–21 days after the denervation was 76%. It decreased to 32% at 6 months and to 22% at 1 year. The median success duration was 17 weeks (95% CI 10–26). The Cox-regression analysis showed a significant shorter duration of success for patients with depression (hazard ratio [HR] 2.97, 95% CI 1.32–6.65), previous surgery (HR 2.39, 95% CI 1.10–5.21) and number of treated joints (HR 1.95 for each increase in the number of joints, 95% CI 1.14–3.33). In bivariate analyses, only depression was kept to be significant. Conclusions Depression seems to be related with a short duration of success. Based on these findings, a comprehensive study is warranted to evaluate whether psychosocial factors have to be considered when recruiting patients for radiofrequency denervation.

Factor analysis of responses to thermal, electrical, and mechanical painful stimuli supports the importance of multi-modal pain assessment

During the last decade, a multi-modal approach has been established in human experimental pain research for assessing pain thresholds and responses to various experimental pain modalities. Studies have concluded that differences in responses to pain stimuli are mainly related to variation between individuals rather than variation in response to different stimulus modalities. In a factor analysis of 272 consecutive volunteers (137 men and 135 women) who underwent tests with different experimental pain modalities, it was determined whether responses to different pain modalities represent distinct individual uncorrelated dimensions of pain perception. Volunteers underwent single painful electrical stimulation, repeated painful electrical stimulation (temporal summation), test for reflex receptive field, pressure pain stimulation, heat pain stimulation, cold pain stimulation, and a cold pressor test (ice water test). Five distinct factors were found representing responses to 5 distinct experimental pain modalities: pressure, heat, cold, electrical stimulation, and reflex-receptive fields. Each of the factors explained approximately 8% to 35% of the observed variance, and the 5 factors cumulatively explained 94% of the variance. The correlation between the 5 factors was near null (median ρ=0.00, range -0.03 to 0.05), with 95% confidence intervals for pairwise correlations between 2 factors excluding any relevant correlation. Results were almost similar for analyses stratified according to gender and age. Responses to different experimental pain modalities represent different specific dimensions and should be assessed in combination in future pharmacological and clinical studies to represent the complexity of nociception and pain experience.

Local pain and spreading hyperalgesia induced by intramuscular injection of nerve growth factor are not reduced by local anesthesia of the muscle

Injections with local anesthesia for therapeutic and diagnostic purposes are common clinical practice. This double-blind placebo controlled study explores the rational of local anesthetic blocks for the detection of muscle pain as the primary generator in spreading hyperalgesic conditions.