Le neuroscienze e la libertà del volere

In the last 30 years, neurosciences, with their mechanistic approach, have dealt with the study of freedom of the will, a field that is considered typical of philosophy or psychology. The studies in neurosciences have been paradoxically appreciated more by philosophers and psychologists than by the scientists themselves, who have straightened the methodological limits. From the considerations of those limits, coming precisely from the neurosciences themselves, rises an interpretation of the freedom of the will that throws a bridge towards positions that are considered typical of philosophical and psychological theories

Differential morphine tolerance development in the modulation of macrophage cytokine production in mice

Morphine has been shown to affect cell-mediated and humoral immune parameters. In this study, we investigated the capacity of in vivo acute and chronic morphine treatment to modulate interleukin (IL)-10 and IL-12 production by LPS and interferon-\u3b3-stimulated resident and thioglycollate-elicited murine peritoneal macrophages and the development of tolerance to these effects. One hour after the acute administration of 5, 10, and 20 mg/Kg morphine, a dose-related decrease of IL-10 and IL-12 levels was present. The pretreatment with naltrexone at doses up to 20 mg/Kg did not prevent the decrease of IL-10 and IL-12 induced by morphine. When the drug was administered chronically, a differential development of tolerance to the immune effects was observed. After 3 days of treatment, the effect of the acute challenge with 20 mg/Kg morphine on IL-12 was lost. In contrast, morphine-induced inhibition of IL-10 disappeared between 10 and 12 days of treatment, in parallel with tolerance to the antinociceptive effect. These results suggest that morphine treatment affects macrophage cytokine production and that tolerance affects this modulation differently

Oppioidi, MDMA, marijuana e l’immunosoppressione : quale rilevanza clinica?

Obiettivi: Lo scopo di questa breve rassegna \ue8 di riassumere i dati disponibili in letteratura sulle interazioni tra alcune sostanze d\u2019abuso, quali le amfetamine e i loro derivati, la marijuana e gli oppioidi, e la funzione immune. L\u2019 importanza di questi aspetti nella medicina dell\u2019addiction non \ue8 ancora chiara. Metodi: Sono state prese in considerazioni le pubblicazioni pi\uf9 significative presenti in Medline, identificate con opportune parole chiave e scelte secondo l\u2019esperienza degli autori sull\u2019argomento. Risultati: Gli effetti sul sistema immune possono essere indiretti, attraverso l\u2019interazioni dei farmaci con recettori o trasportatori presenti nel sistema nervoso centrale o attraverso l\u2019attivazione di recettori espressi dalle cellule immuni. In particolare per la marijuana e gli oppioidi sono stati chiaramente identificati i recettori specifici su tutte le popolazioni di cellule immuni. Un aspetto comune della immunomodulazione di tutte le sostanze d\u2019abuso sembra essere quello di perturbare l\u2019equilibrio omeostatico tra i linfociti Thelper1, pro infiammatori, in favore dei Thelper 2, di tipo antinfiammatori. Esiste quindi oggi un\u2019ampia letteratura che dimostra come le sostanze d\u2019abuso alterino la funzione immune nell\u2019animale da esperimento e in vitro anche in cellule umane. Nell\u2019animale da esperimento inoltre \ue8 sempre pi\uf9 chiara l\u2019esistenza di una correlazione tra l\u2019effetto immunosoppressivo e l\u2019incidenza di infezioni. L\u2019elevata incidenza di patologie infettive nei soggetti che abusano di sostanze \ue8 ben nota, ma molto pochi sono ancora gli studi nell\u2019uomo che cercano di correlare gli effetti immunosoppressivi con la maggior suscettibilit\ue0 alle infezioni. Conclusione: L\u2019effetto immunosoppressivo dei farmaci d \u2018abuso \ue8 stato ben documentato. Nell\u2019uomo per\uf2 non \ue8 possibile al momento dimostrare l\u2019esistenza di una relazione di causa effetto tra questi effetti ed un aumentato rischio di infezioni. Ulteriori studi saranno necessari per meglio comprendere questo aspetto

Preliminary study on the effect of size of individual stall on the behavioural and immune reactions of dairy calves

Ten Italian Friesian female calves were housed in individual stalls of two different dimensions (0.73 m x 1.21 m vs 1.00 m x 1.50 m) during the Ist month of life in order to evaluate the effect of space on the welfare of dairy calves. Behavioural observations were made on d 2 to 3 (period 1) and on d 28 to 29 (period 2) during daylight using a time-lapse video recording system. At 10, 20, and 30 d, blood samples were taken and analysed with phytohemagglutinin stimulation to determine lymphocyte proliferation. During the second period, the calves in large stall spent more time lying (P<0.05) and grooming (P<0.001), and the calves in small stalls exhibited more time searching for feed (P<0.001). Lymphocyte proliferation was statistically lower in calves housed in smaller stalls (P<0.01). Moreover, lymphocyte proliferation was negatively correlated with time spent searching for feed (P<0.01)

The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients

There has been growing interest in determining the possible immune consequences of opioid administration for the management of postoperative pain. We studied the effects of morphine and tramadol on pain and immune function during the postoperative period in 30 patients undergoing abdominal surgery for uterine carcinoma. Phytohemoagglutinin-induced T lymphocyte proliferation and natural killer cell activity were evaluated immediately before and after surgery, and 2 h after the acute administration of either 10 mg of morphine IM or 100 mg tramadol IM for pain. In all patients, phytohemagglutinin-induced lymphoproliferation was significantly depressed by surgical stress. However, in the morphine-treated group, proliferative values remained lower than basal levels for 2 h after treatment, whereas in tramadol-administered patients proliferative values returned to basal levels. Natural killer cell activity was not significantly affected by surgery nor by morphine administration, whereas tramadol significantly enhanced the activity of natural killer cells. Both drugs produced a comparable reduction in postoperative pain. We conclude that, as previously observed in the experimental animal, tramadol and morphine, when administered in analgesic doses, induce different immune effects

Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy

Over the last decade it has been proved that Mesenchymal Stem Cells (MSCs) elicit anti-inflammatory effects. Mesenchymal Stem Cells from adipose tissue (hASCs) differentiate into cells of mesodermal lineage and trans-differentiate into ectodermal origin cells. Though there are various etiologies to chronic pain, one common feature is that painful states are associated with increased inflammation. We believe in hASCs as an therapeutic tool also in pathologies involving neuro-inflammation and neuronal-tissue damage. We have investigated the effect of hASCs injected in a model of neuropathic pain (mouse sciatic nerve Chronic Constriction Injury-CCI). hASCs from 5 donors were characterized, and no major differences were depicted. hASCs were cryopreserved and grown on demand. 1x106, 3x106 and 6x106 hASCs were intravenously injected into normal immunocompetent mice. No mouse died and no macroscopic toxicity or behavioral changes were observed, confirming the safety of hASCs. hASCs, i.v. injected into C57BL/6 mice, when the neuropathic pain was already established, induced a significant reduction in mechanical allodynia and a complete reversion of thermal hyperalgesia in a dose response fashion, already 1 day after administration. Moreover, the hASCs effect can be boosted by repeated administrations, allowing a prolonged therapeutic effect. Treatment decreased the level of the CCI-induced pro-inflammatory cytokine IL-1\u3b2 and activated the anti-inflammatory cytokine IL-10 in the lesioned nerve. hASC treatment also restored normal inducible Nitric Oxide Synthase (iNOS) expression in the CCI animals spinal cord. Our data suggest that hASCs are worthy further studies as anti-inflammatory therapy in the treatment of neuropathic pain or chronic inflammatory diseases

Pain emotion and homeostasis

Pain has always been considered as part of a defensive strategy, whose specific role is to signal an immediate, active danger. This definition partially fits acute pain, but certainly not chronic pain, that is maintained also in the absence of an active noxa or danger and that nowadays is considered a disease by itself. Moreover, acute pain is not only an automatic alerting system, but its severity and characteristics can change depending on the surrounding environment. The affective, emotional components of pain have been and are the object of extensive attention and research by psychologists, philosophers, physiologists and also pharmacologists. Pain itself can be considered to share the same genesis as emotions and as a specific emotion in contributing to the maintenance of the homeostasis of each unique subject. Interestingly, this role of pain reaches its maximal development in the human; some even argue that it is specific for the human primate

Pain stress and headache

The association between pain and stress is an old one, but still it is not really clear who comes first. Pain induces stress, and stress induces pain. Pain is part of our homeostatic system and in this way is an emotion, i.e., it tells us that something is out-of-order (control), and emotion drives our behavior and one behavior is stress response. Stress comes from ourselves: the imagination we have or would like to have of us, from the image others give of us, from the goals we assume it is necessary to reach for our well-being or the goals others want us to fulfill. Stress comes from our social condition and the condition we would like, stress comes from dangerous situations we cannot control. Headache easily fits in the picture

Is migraine a disorder of the central nervous system?

The chicken and the egg problem is how, in Italian or in English, some time ago one would have referred to a question as the one to be approached here: "Is migraine a disorder of the central nervous system?" or of the peripheral nervous system? Till some time ago, even an honest basic scientist or clinician could almost equally sustain one or the other origin and find data that substantiate her/his opinion. Nowadays, however, our improved knowledge is pushing in the direction of the central nervous system, although many mechanisms remain unclear. The confusion originates from the important role played by multiple and important bidirectional interactions between the peripheral and the central nervous systems, i.e., the trigeminovascular system and the cerebral cortex. The problems are: Who starts first? Who is not working properly? It appears now that the answer to the question has to be probably searched in the delicate balance present in the central nervous system between excitatory and inhibitory circuits, their adaptation to chronic stimuli and, within these circuits, the balance of neurotransmitters, neuromodulators, transporters and ion channels that keeps them well functioning