Early transplantation of mesenchymal stem cells after spinal cord injury relieves pain hypersensitivity through suppression of pain-related signaling cascades and reduced inflammatory cell recruitment

Bone marrow-derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC-based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)-positive bone marrow-chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post-SCI improved motor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C-γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (p-ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double-positive hematogenous macrophages without decreasing the CD11b-positive and GFP-negative activated spinal-microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood-spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor-α, interleukin-6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte-macrophage colony-stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal-resident microglia and the activity and recruitment of hematogenous macrophages.

Electric shock causes physiological stress responses in shore crabs, consistent with prediction of pain

Animal pain is defined by a series of expectations or criteria, one of which is that there should be a physiological stress response associated with noxious stimuli. While crustacean stress responses have been demonstrated they are typically preceded by escape behaviour and thus the physiological change might be attributed to the behaviour rather than a pain experience. We found higher levels of stress as measured by lactate in shore crabs exposed to brief electric shock than non-shocked controls. However, shocked crabs showed more vigorous behaviour than controls. We then matched crabs with the same level of behaviour and still found that shocked crabs had stronger stress response compared with controls. The finding of the stress response, coupled with previous findings of long-Term motivational change and avoidance learning, fulfils the criteria expected of a pain experience.

Nurses' experiences of pain management for people with advanced dementia approaching the end of life: a qualitative study

AIMS AND OBJECTIVES: To explore hospice, acute care and nursing home nurses' experiences of pain management for people with advanced dementia in the final month of life. To identify the challenges, facilitators and practice areas requiring further support.

BACKGROUND: Pain management in end-stage dementia is a fundamental aspect of end of life care; however, it is unclear what challenges and facilitators nurses experience in practice, whether these differ across care settings, and whether training needs to be tailored to the context of care.

DESIGN: A qualitative study using semi-structured interviews and thematic analysis to examine data.

METHODS: 24 registered nurses caring for people dying with advanced dementia were recruited from ten nursing homes, three hospices, and two acute hospitals across a region of the United Kingdom. Interviews were conducted between June 2014 and September 2015.

RESULTS: Three core themes were identified: challenges administering analgesia, the nurse-physician relationship, and interactive learning and practice development. Patient-related challenges to pain management were universal across care settings; nurse- and organisation-related barriers differed between settings. A need for interactive learning and practice development, particularly in pharmacology, was identified.

CONCLUSIONS: Achieving pain management in practice was highly challenging. A number of barriers were identified; however, the manner and extent to which these impacted on nurses differed across hospice, nursing home and acute care settings. Needs-based training to support and promote practice development in pain management in end-stage dementia is required.

RELEVANCE TO CLINICAL PRACTICE: Nurses considered pain management fundamental to end of life care provision; however, nurses working in acute care and nursing home settings may be under-supported and under-resourced to adequately manage pain in people dying with advanced dementia. Nurse-to-nurse mentoring and ongoing needs-assessed interactive case-based learning could help promote practice development in this area. Nurses require continuing professional development in pharmacology. This article is protected by copyright. All rights reserved.

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area.

The Effects of Instrumental Touching on Infant Pain Perception and the Effects of Eutectic Mixture of Local Anesthetics (EMLA) on the Reduction of Pain

Background: Premature infants, who have to spend the first week of their lives in neonatal intensive care units (NICUs), experience pain and stress in numerous cases, and they are exposed to many invasive interventions. The studies have shown that uncontrolled pain experienced during early life has negative and long-term side effects, such as distress, and such experiences negatively affect the development of the central nervous system Objectives: The purpose of the study was to examine the effects of touching on infant pain perception and the effects of eutectic mixture of local anesthetic (EMLA) on the reduction of pain. Patients and Methods: Data for the study were collected between March and August 2012 from the neonatal clinic of a university hospital located in eastern Turkey. The population of the study consisted of premature infants who were undergoing treatment, completed the first month and who were approved for Hepatitis B vaccine. The study consisted of two experimental groups and one control group. Information forms, intervention follow-up forms, and Premature Infant Pain Profile (PIPP) were used to collect the data. EMLA cream was applied on the vastus lateralis muscles of the first experimental group before the vaccination. The second experimental group was vaccinated by imitation (placebo), without a needle tip or medicine. Vaccination was carried out using instrumental touch in this group. A routine vaccination was applied in the control group. Results: Mean pain scores of the group to which EMLA was applied were lower in a statistically significant way (P < 0.05) compared to the pain scores of the other groups. Moreover, it was determined that even though invasive intervention was not applied to the newborns, the touching caused them to feel pain just as in the placebo group (P < 0.005). Conclusions: The results demonstrated that EMLA was an effective method for reducing pain in premature newborns, and the use of instrumental touch for invasive intervention stimulated the pain perception in the newborns.

Angústia de morte sentida pelos profissionais de saúde, face aos doentes em fase terminal

O presente trabalho aborda as dificuldades sentidas pelos profissionais de saúde perante os doentes em fase terminal. É importante percebermos como é que os profissionais de saúde se preparam psicologicamente para tratar dos pacientes com o profissionalismo que lhes é pedido. O trabalho recai, na tentativa de verificar, a forma como conseguem “escapar” a esta ligação directa com a morte. Participaram neste estudo do tipo exploratório, 4 enfermeiras e 1 médica da Unidade da Dor do Hospital Garcia de Orta, que através de entrevistas semi-directivas, descreviam as suas experiências. Abordámos o percurso profissional, as dificuldades no dia-a-dia, as situações mais gratificantes, a função da equipa e o processo de luto. Nos resultados obtidos, utilizámos como método a análise de conteúdo. Os resultados destacaram a identificação, como a maior dificuldade, lembrando desta forma que os profissionais de saúde, também sofrem com a perda dos doentes, como se de alguém próximo se tratasse, complicando a relação profissional e levando a que normalmente se usem mecanismos do evitamento. Concluímos que é indispensável o apoio da equipa multidisciplinar, de forma a acolher todos os acontecimentos que provocam desconforto e angústia em relação à morte, por mais mecanismos utilizados é impossível dissociar a relação profissional da pessoal.

Mastication Movements And Sleep Quality Of Patients With Myofascial Pain: Occlusal Device Therapy Improvements.

Patients with myofascial pain experience impaired mastication, which might also interfere with their sleep quality. The purpose of this study was to evaluate the jaw motion and sleep quality of patients with myofascial pain and the impact of a stabilization device therapy on both parameters. Fifty women diagnosed with myofascial pain by the Research Diagnostic Criteria were enrolled. Pain levels (visual analog scale), jaw movements (kinesiography), and sleep quality (Epworth Sleepiness Scale; Pittsburgh Sleep Quality Index) were evaluated before (control) and after stabilization device use. Range of motion (maximum opening, right and left excursions, and protrusion) and masticatory movements during Optosil mastication (opening, closing, and total cycle time; opening and closing angles; and maximum velocity) also were evaluated. Repeated-measures analysis of variance in a generalized linear mixed models procedure was used for statistical analysis (α=.05). At baseline, participants with myofascial pain showed a reduced range of jaw motion and poorer sleep quality. Treatment with a stabilization device reduced pain (P<.001) and increased both mouth opening (P<.001) and anteroposterior movement (P=.01). Also, after treatment, the maximum opening (P<.001) and closing (P=.04) velocities during mastication increased, and improvements in sleep scores for the Pittsburgh Sleep Quality Index (P<.001) and Epworth Sleepiness Scale (P=.04) were found. Myofascial pain impairs jaw motion and quality of sleep; the reduction of pain after the use of a stabilization device improves the range of motion and sleep parameters.

Two-dimensional Ultrasound And Ultrasound Elastography Imaging Of Trigger Points In Women With Myofascial Pain Syndrome Treated By Acupuncture And Electroacupuncture: A Double-blinded Randomized Controlled Pilot Study.

Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects.

Reduction Of Blood Nitric Oxide Levels Is Associated With Clinical Improvement Of The Chronic Pelvic Pain Related To Endometriosis.

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

The contribution of self-efficacy and depression to disability and work status in chronic pain patients: A comparison between Australian and Brazilian samples

There is evidence that cognitions (beliefs) and mood contribute to physical disability and work status in people with chronic pain. However, most of the current evidence comes from North America and Europe. This study examined the contribution of demographic, pain and psychosocial factors to disability and work status in chronic pain patients in two matched samples from quite different countries (Australia and Brazil). Data were collected from 311 chronic pain patients in each country. The results suggest that although demographic and pain variables (especially pain levels) contribute disability, self-efficacy beliefs made a significant contribution to disability in both samples. Age and educational level also contributed to unemployment in both samples. But there were some differences, with self-efficacy and physical disability contributing to work status only in the Brazilian sample. In contrast, depression was the only psychological risk factor for unemployment in the Australian sample. Catastrophising and pain acceptance did not contribute to disability or unemployment in either sample. These findings confirm key aspects of biopsychosocial models of pain in two culturally and linguistically different chronic pain samples from different countries. They suggest that different chronic pain populations may share more similarities than differences. (C) 2008 European Federation of Chapters of the International Association for the Study of Pain. Published

Understanding Pain and Quality of Life for Patients With Chronic Venous Ulcers

Aim. To identify the impact of pain on quality of life (QOL) of patients with chronic venous ulcers. Methods. A cross-sectional study was performed on 40 outpatients with chronic venous ulcers who were recruited at one outpatient care center in Sao Paulo, Brazil. WHOQOL-Bref was used to assess QOL, the McGill Pain Questionnarie-Short Form (MPQ) to identify pain characteristics, and an 11-point numerical pain rating scale to measure pain intensity. Kruskall-Wallis or ANOVA test, with post-hoc correction (Tukey test) was applied to compare groups. Multiple linear regression models were used. Results. The mean age of the patients was 67 +/- 11 years (range, 39-95 years), and 26 (65%) were women. The prevalence of pain was 90%, with worst pain mean intensity of 6.2 +/- 3.5. Severe pain was the most prevalent (21 patients, 52.5%). Pain most frequently reported was sensory-discriminative and evaluate in quality. Pain was significantly and negatively correlated with physical (PY), environmental (EV), and overall QOL. Compared to a no-pain group, those with pain had lower overall QOL. On multiple analyses, pain remained as a predictor of overall QOL (beta = -0.73, P = 0.03) and was also predictive of social QOL, whereas pain did not have any impact on physical, emotional, or social relationships QOL (beta = -3.85, P = 0.00) when adjusted for age, number, duration and frequency of wounds, pain dimension (MPQ), partnership, and economic status. Conclusion. To improve QOL of out-patients with chronic venous ulcers, the qualities and the intensity of pain must be considered differently.

Identification and Validation of Brazilian Chronic Pain Descriptors

Appropriate pain assessment is very important for managing chronic pain. Given the cultural differences in verbally expressing pain and in psychosocial problems, specific tools are needed. The goal of this study was to identify and validate Brazilian pain descriptors. A purposive sample of health professionals and chronic pain patients was recruited. Four studies were conducted using direct and indirect psychophysical methods: category estimation, magnitude estimation, and magnitude estimation and tine-length. Results showed the descriptors which best describe chronic pain in Brazilian culture and demonstrated that there is not a significant correlation between patients and health professionals and that the psychophysical scale of judgment of pain descriptors is valid, stable, and consistent. Results reinforced that the translations of word descriptors and research tools into another language may be inappropriate, owing to differences in perception and communication and the inadequacy of exact translations to reflect the intended meaning. Given the complexity of the chronic pain, personal suffering involved, and the need for accurate assessment of chronic pain using descriptors stemming from Brazilian culture and language, it is essential to investigate the most adequate words to describe chronic pain. Although it requires more refinement, the Brazilian chronic pain descriptors can be used further to develop a multidimensional pain assessment tool that is culturally sensitive. (C) 2009 by the American Society for Pain Management Nursing