Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease

The prevention of analgesic opioids abuse: expert opinion

Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship

An observational study on chronic pain biomarkers in fibromyalgia and osteoarthritis patients:.which role for mu opioid receptor’s expression on NK cells.

The evaluation of chronic pain is challenging because of the lack of specific biomarkers. We identified the Mu opioid receptor-positive (Mu+) B cell percentage of expression, named Mu-Lympho-Marker (MLM), as a candidate marker for chronic pain in fibromyalgia (FM) and osteoarthritis (OA) patients. Here, we investigate the role of MLM on natural killer (NK) cells in the same patients. Twenty-nine FM and twelve OA patients were analyzed, and twenty-three pain-free subjects were considered as the control group. Blood samples were collected to perform immunophenotyping and Western blot analysis. Biological and clinical data were statistically analyzed. The final results showed that the percentage of NK cells expressing Mu was statistically lower in FM and OA patients than in pain-free subjects, as already demonstrated for B cells. A Western blot analysis was performed in order to detect NK cells' functional status. Moreover, the correlation analysis of MLM expression with pharmacological therapy did not show any significant results. In conclusion, here, we confirm the role of MLM as a suitable marker for chronic pain and underline NK cells as a new possible immune cell type involved in the "Mu opioid receptor reserve theory"

Carbonaceous and siliceous Neoproterozoic vase-shaped microfossils (Urucum Formation, Brazil) and the question of early protistan biomineralization.

Vase-shaped microfossils (VSMs) occur in dolomitic extraclasts of indeterminate provenance within the basal diamictite of the Neoproterozoic Urucum Formation (Jacadigo Group) of west-central Brazil, having an age constrained between 889?44 Ma (K-Ar; basement rocks) and 587?7 Ma (40Ar/39Ar age of early metamorphic cryptomelane in overlying manganese ore). Early isopachous carbonate cement entombed these VSMs, preserving rare direct evidence of original wall composition that is carbonaceous (now kerogenous) in practically all specimens. Some tests are siliceous or composed of a quartz-kerogen mixture; secondary replacement explains some features of these tests, but original biomineralization seems more likely for others. This interpretation, coupled with test morphology, suggests affinity to arcellinid testate amoebae. Five VSM taxa are recognized in the deposit: Cycliocyrillium simplex Porter, Meisterfeld, and Knoll, 2003, and C. torquata Porter, Meisterfeld, and Knoll, 2003, originally described in the Chuar Group (USA), and three new monospecific genera?Palaeoamphora urucumense n. gen. n. sp., Limeta lageniformis n. gen. n. sp., and Taruma rata n. gen. n. sp. Most of the taxonomically important characteristics of these VSMs occur also in extant testate amoebae, but the combinations of some characters, such as organic-walled tests having exceptionally long necks that exhibit terminal apertures (L. lageniformis n. gen. n. sp.), are evidently novel additions to the known diversity of Neoproterozoic VSMs. Evidence of glacially influenced deposition in the conformably overlying Santa Cruz Formation may indicate that the Urucum Formation slightly preceded or was penecontemporaneous with a major Neoproterozoic glaciation, although the VSM-hosting extraclasts must be older, possibly rivaling the age of the testate amoebae of the Chichkan Formation (766?7 Ma) that are currently regarded as the oldest record of protists in the geological record

Pain assessment in animal models: do we need further studies?

In the last two decades, animal models have become important tools in understanding and treating pain, and in predicting analgesic efficacy. Although rodent models retain a dominant role in the study of pain mechanisms, large animal models may predict human biology and pharmacology in certain pain conditions more accurately. Taking into consideration the anatomical and physiological characteristics common to man and pigs (median body size, digestive apparatus, number, size, distribution and communication of vessels in dermal skin, epidermal–dermal junctions, the immunoreactivity of peptide nerve fibers, distribution of nociceptive and non-nociceptive fiber classes, and changes in axonal excitability), swines seem to provide the most suitable animal model for pain assessment. Locomotor function, clinical signs, and measurements (respiratory rate, heart rate, blood pressure, temperature, electromyography), behavior (bright/quiet, alert, responsive, depressed, unresponsive), plasma concentration of substance P and cortisol, vocalization, lameness, and axon reflex vasodilatation by laser Doppler imaging have been used to assess pain, but none of these evaluations have proved entirely satisfactory. It is necessary to identify new methods for evaluating pain in large animals (particularly pigs), because of their similarities to humans. This could lead to improved assessment of pain and improved analgesic treatment for both humans and laboratory animals

Du symptôme douleur à la maladie douleur

Le terme « douleur » est depuis toujours synonyme de « symptôme », conviction profondément enracinée chez les médecins et le personnel soignant, les malades et dans l’opinion publique. Mais la douleur considérée comme un symptôme est le fruit d’une lecture simpliste du phénomène : il y a en fait des situations où la douleur ne peut pas être considérée comme un symptôme mais comme une véritable Maladie liée à deux différentes conditions, c’est-à-dire une de « douleur idiopathique essential » et une de « douleur chronique causée par un trouble post-causal » et où, dans les deux cas, la pathogenèse n’est pas liée à d'autres causes. Il faut encore travailler pour étayer scientifiquement et précisément l’hypothèse selon laquelle la douleur, dans certaines conditions, est une pathologie avec un statut de maladie à part entière. Pour soutenir ce postulat, je crois par ailleurs qu’il est nécessaire de réorganiser une discipline scientifique qui renferme de nombreuses faces cachées qu’elle ne veut pas voir, mais qui apparaissent pourtant de manière évidente à travers l’histoire clinique de nombreuses personnes. Il est temps que l’univers douleur revendique son identité nosologique.The term “pain” has always been synonymous of "symptom" and this belief is deeply rooted in the professional medical class, in the nursing care, in the public opinion and in the patients. But considering pain as a simple symptom is the result of a simplistic interpretation of the phenomenon: there are situations where pain can not be considered as a symptom but as a real, concrete state of illness that can be related to two different conditions, namely the “idiopathic essential pain” and “chronic pain caused by a post-causal dysfunction”. In both cases the pathogenesis is not related to any other causes. It is still necessary to work and study in order to document in a scientifically precise manner the hypothesis that pain is, in certain conditions, a pathology with its own disease status. In support of this postulate I believe that medical science, which doesn’t take into account some crucial points that are, on the contrary, crearly presents in the patients’ clinical histories, must be reorganized. It is time for the universe of pain to reclaim its own nosological identity

La percezione del dolore cronico quale problema sanitario in due popolazioni con e senza esperienza di dolore cronico - Perception of chronic pain as a healthcare issue in two populations with and without chronic pain esperience

Chronic pain is recognized today as a major healthcare issue. Notwithstanding the extent of the data available, public information concerning the treatment options for this condition remains unsatisfactory in Italy as in the rest of the world. During the seventh edition held in 2015 of the international Day “Hundred Cities against Pain” organized by Fondazione ISAL, a questionnaire has been distributed in order to investigate the perceptions and perspectives of people towards chronic pain prevention and treatment. In this work, the results of the survey are reported with the aim of shedding light on some issues related to the needs and perceptions of the citizens in relation to the disease of chronic pain and the access to treatment sanctioned by Italian law 38/2010

Long-term intrathecal morphine influence on major compounds of the endocrine system in elderly population

Abstract Background The influence of long-term opioid administration on hormonal levels is not well characterized in the literature. We previously showed that intrathecal opioid therapy significantly influences the homeostasis of immune and endocrine systems. Other authors confirmed that exogenous and endogenous opioids induce this effect. They have a cytokine-like behavior and may function as neurotransmitters, neuromodulators or hormones, as concerning their synthesis, storage and release. Aims To assess the effects of morphine long-term intrathecal administration on serum levels of Gonadal, Thyroidal and Adrenal axis hormones in an elderly population affected by chronic pain; to assess the correlation between hormone levels and morphine dosage. Methods Patients suffering from chronic non-cancer pain with or without intrathecal drug delivery system were studied and hormonal levels were monitored, using an immunoradiometric assay kit. Results The long-term administration of intrathecal morphine influenced part of the endocrine system, in particular, there was a reduction of FSH and LH and an increment of GH serum levels; this effect was morphine dose dependent. Conclusion Long-term intrathecal opioid administration influenced FSH, LH and GH serum levels. Data on this issue are inadequately described in the literature. The finding of endocrine effects of opioid therapy, nonetheless, cannot be ignored, as it may have clinical relevance in both elderly and young population. We believe that during long intrathecal pain treatments with morphine, clinicians should be aware of both immediate and later opioids side effects, and in particular, they should monitor immune and endocrine changes