Pharmacological modulation of beta-endorphin in rat peritoneal macrophages.

The neuropeptide beta-endorphin is present in cells of the immune system, i.e., lymphocytes and monocytes, and its expression can be induced by immunological stimuli. In the present study, we showed that the increase of the serotoninergic availability induces an increase of beta-endorphin concentrations in rat peritoneal macrophages that is blunted by the administration of serotonin receptor antagonists. A significant increase of beta-endorphin concentrations is also evident after blocking the dopaminergic receptors, whereas a dopaminergic agonist decreases the concentrations of the peptide. Our data are consistent with a similar modulation of beta-endorphin concentrations in central nervous system and in immune cells, e.g., rat peritoneal macrophages

The prokineticin system : an interface between neural inflammation and pain

Prokineticins (PK) 1 and 2 belong to a new family of chemokines capable to interact with two different G coupled receptors: Prokineticin receptor (PKR)1 and 2. Both prokineticins and their receptors are widely distributed in different tissues and regulate several biological functions. In particular, a role of the PK system in inflammation and nociception has been established. PKRs are expressed in regions of the nervous system associated with pain and in primary sensitive neurons they colocalize with transient potential receptor vanilloid-TRPV1 providing an anatomical interaction in nociceptor sensitization. Moreover, PKs are strongly upregulated in immune and glial cells and sustain a proinflammatory loop in inflamed tissues. Recent evidences indicate that the block of the PK system represents a promising strategy to contrast inflammation and pain

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

Microscale Modeling of High-Temperature Heat Transfer in Anisotropic Porous Materials

No abstract availabl

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)

Immune function after major surgical interventions : the effect of postoperative pain treatment

Introduction: Impaired immune function during the perioperative period may be associated with worse short- and long-term outcomes. Morphine is considered a major contributor to immune modulation. Patients and methods: We performed a pilot study to investigate postoperative immune function by analyzing peripheral blood mononuclear cells' functionality and cytokine production in 16 patients undergoing major abdominal surgery. All patients were treated with intravenous (i.v.) patient-controlled analgesia with morphine and continuous wound infusion with ropivacaine+methylprednisolone for 24 hours. After 24 hours, patients were randomized into two groups, one continuing intrawound infusion and the other receiving only i.v. analgesia. We evaluated lymphoproliferation and cytokine production by peripheral blood mononuclear cells at the end of surgery and at 24 and 48 hours postoperatively. Results: A significant reduction in TNF-\u3b1, IL-2, IFN-\u3b3 and lymphoproliferation was observed immediately after surgery, indicating impaired cell-mediated immunity. TNF-\u3b1 and IFN-\u3b3 remained suppressed up to 48 hours after surgery, while a trend to normalization was observed for IL-2 and lymphoproliferation, irrespective of the treatment group. A significant inverse correlation was present between age and morphine and between age and lymphoproliferation. No negative correlation was present between morphine and cytokine production. We did not find any differences within the two groups between 24 and 48 hours in terms of morphine consumption and immune responses. Conclusion: A relevant depression of cell-mediated immunity is associated with major surgery and persists despite optimal analgesia. Even though morphine may participate in immunosuppression, we did not retrieve any dose-related effect

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

Adult stem cell as new advanced therapy for experimental neuropathic pain treatmen

Neuropathic pain (NP) is a highly invalidating disease resulting as consequence of a lesion or disease affecting the somatosensory system. All the pharmacological treatments today in use give a long lasting pain relief only in a limited percentage of patients before pain reappears making NP an incurable disease. New approaches are therefore needed and research is testing stem cell usage. Several papers have been written on experimental neuropathic pain treatment using stem cells of different origin and species to treat experimental NP. The original idea was based on the capacity of stem cell to offer a totipotent cellular source for replacing injured neural cells and for delivering trophic factors to lesion site; soon the researchers agreed that the capacity of stem cells to contrast NP was not dependent upon their regenerative effect but was mostly linked to a bidirectional interaction between the stem cell and damaged microenvironment resident cells. In this paper we review the preclinical studies produced in the last years assessing the effects induced by several stem cells in different models of neuropathic pain. The overall positive results obtained on pain remission by using stem cells that are safe, of easy isolation, and which may allow an autologous transplant in patients may be encouraging for moving from bench to bedside, although there are several issues that still need to be solved

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