The Prokineticin System in Inflammatory Bowel Diseases: A Clinical and Preclinical Overview.

Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC), which are characterized by chronic inflammation of the gastrointestinal (GI) tract. IBDs clinical manifestations are heterogeneous and characterized by a chronic relapsing-remitting course. Typical gastrointestinal signs and symptoms include diarrhea, GI bleeding, weight loss, and abdominal pain.

Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine.

Rationale: Asteoarthritis (OA) is a leading cause of chronic pain in the elderly population and is often associated with emotional comorbidities such as anxiety and depression. Despite age is a risk factor for both OA and mood disorders, preclinical studies are mainly conducted in young adult animals.

Objectives: Here, using young adult (11-week-old) and older adult (20-month-old) mice, we evaluate in a monosodium-iodoacetate-(MIA)-induced OA model the development of anxio-depressive-like behaviors and whether brain neuroinflammation may underlie the observed changes.

Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results.

Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important mediators of inflammation and pain. This observational study examined the potential involvement of PK2 in degenerative or traumatic knee disease.

Characterization of prokineticin system in Crohn's disease pathophysiology and pain, and its modulation by alcohol abuse: A preclinical study.

Background: Crohn's disease-(CD) pathogenesis is still unknown and chronic pain is a frequent symptom in CD-patients. Identifying novel therapeutic targets and predisposing factors is a primary goal. In this regard, prokineticin system-(PKS) appears a promising target.

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking.

Frailty and pain, human studies and animal models.

The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms.

Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy.

Chemotherapy-induced neuropathy (CIN) is a major adverse effect associated with many chemotherapeutics, including bortezomib (BTZ). Several mechanisms are involved in CIN, and recently a role has been proposed for prokineticins (PKs), a chemokine family that induces proinflammatory/pro-algogen mediator release and drives the epigenetic control of genes involved in cellular differentiation. The present study evaluated the relationships between epigenetic mechanisms and PKs in a mice model of BTZ-induced painful neuropathy.

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations.

The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation.

Resolvin E1 and Cytokines Environment in Skeletally Immature and Adult ACL Tears.

The intra-articular synovial fluid environment in skeletally immature patients following an ACL tear is complex and remains undefined. Levels of inflammatory and anti-inflammatory cytokines change significantly in response to trauma and collectively define the inflammatory environment. Of these factors the resolvins, with their inherent anti-inflammatory, reparative, and analgesic properties, have become prominent.

Secretome of human adipose-derived mesenchymal stem cell relieves pain and neuroinflammation independently of the route of administration in experimental osteoarthritis.

Objective: Treatment of pain associated with osteoarthritis (OA) is unsatisfactory and innovative approaches are needed. The secretome from human adipose-derived mesenchymal stem cells (hASC-Conditioned Medium, CM) has been successfully used to relieve painful symptoms in models of chronic pain. The aim of this study was to explore the efficacy of the hASC-CM to control pain and neuroinflammation in an animal model of OA.

Pain in Women: A Perspective Review on a Relevant Clinical Issue that Deserves Prioritization.

Introduction: Gender equity and gender medicine are opportunities not to be missed, and this Expert Group Opinion Paper on pain in women aims to review the treatment of pain conditions mainly affecting women, as well as the fundamental aspects of the different clinical response to drug treatment between the genders, and what can be done for gender-specific rehabilitation.

Methods: Perspective review.

Results: Genotypic and phenotypic differences in pain between the sexes are conditioned by anatomical, physiological, neural, hormonal, psychological, social, and cultural factors, such as the response to pharmacological treatment to control pain.

Characterization of Synovial Cytokine Patterns in Bucket-Handle and Posterior Horn Meniscal Tears.

The specific etiology of meniscal tears, including the mechanism of lesion, location, and orientation, is considered for its contribution to subsequent joint cytokine responsiveness, healing outcomes, and by extension, appropriate lesion-specific surgical remediation. Meniscal repair is desirable to reduce the probability of development of posttraumatic osteoarthritis (PTOA) which is strongly influenced by the coordinate generation of pro- and anti-inflammatory cytokines by the injured cartilage. We now present biochemical data on variation in cytokine levels arising from two particular meniscal tears: bucket-handle (BH) and posterior horn (PH) isolated meniscal tears.

Prokineticin Receptor Inhibition With PC1 Protects Mouse Primary Sensory Neurons From Neurotoxic Effects of Chemotherapeutic Drugs .

Neurotoxicity is a common side effect of chemotherapeutics that often leads to the development of chemotherapy-induced peripheral neuropathy (CIPN). The peptide Prokineticin 2 (PK2) has a key role in experimental models of CIPN and can be considered an insult-inducible endangering mediator. Since primary afferent sensory neurons are highly sensitive to anticancer drugs, giving rise to dysesthesias, the aim of our study was to evaluate the alterations induced by vincristine (VCR) and bortezomib (BTZ) exposure in sensory neuron cultures and the possible preventive effect of blocking PK2 signaling.

Measurement of Macrophage Toll-Like Receptor 4 Expression After Morphine Treatment.

The immune system is a complex and finely orchestrated system, and many soluble molecules and receptors contribute to its regulation.Recent studies have suggested that many of the modulatory effects induced by morphine on innate immunity, and in particular the effects on macrophage activation and function, can be due to the modulation of an important macrophage surface receptor, the toll-like receptor (TLR), that is primarily involved in early regulatory steps. In this chapter we describe a RT-real-time PCR method for assessing TLR expression in macrophage after in vivo morphine treatment.

Evaluation of Murine Macrophage Cytokine Production After In Vivo Morphine Treatment.

The discovery of opioid receptor expression on immune cells has originated a large research activity on the possible modulation by opioid drugs of immune system responses. In this chapter we describe an easy methodology useful to obtain information about the potential immunomodulatory activity of opioid drugs. An in vivo treatment schedule is used, and macrophages are studied for their ability to release different cytokines.

Topical treatment of radiation-induced dermatitis: current issues and potential solutions.

Approximately 95% of patients receiving radiotherapy (RT) will ultimately develop radiation-induced dermatitis (RID) during or after the course of treatment, with major consequences on quality of life and treatment outcomes. This paper reviews the pathophysiology of RID and currently used topical products for the prevention and treatment of RID. Although there is no consensus on the appropriate management, recent evidence suggests that the use of topical products supports to protect and promote tissue repair in patients with RID.

Do All Opioid Drugs Share the Same Immunomodulatory Properties? A Review From Animal and Human Studies.

Suppression of the immune system has been constantly reported in the last years as a classical side effect of opioid drugs. Most of the studies on the immunological properties of opioids refer to morphine. Although morphine remains the "reference molecule," other semisynthetic and synthetic opioids are frequently used in the clinical practice.

Prokineticin 2 promotes and sustains neuroinflammation in vincristine treated mice: Focus on pain and emotional like behavior.

Vincristine (VCR) treatment is often associated to painful neuropathy. Its development is independent from antitumoral mechanism and involves neuroinflammation. We investigated the role of the chemokine prokineticin (PK)2 in a mouse model of VCR induced neuropathy using a PK-receptors (PK-R) antagonist to counteract its development.

Layer- and subregion-specific electrophysiological and morphological changes of the medial prefrontal cortex in a mouse model of neuropathic pain.

Chronic neuropathic pain constitutes a serious public health problem, but the disease mechanisms are only partially understood. The involvement of different brain regions like the medial prefrontal cortex has already been established, but the comparison of the role of different subregions and layers is still inconclusive. In the current study, we performed patch-clamp recordings followed by anatomical reconstruction of pyramidal cells from different layers of the prelimbic and infralimbic subregions of the medial prefrontal cortex in neuropathic (spared nerve injury, SNI) and control mice.

Targeting prokineticin system counteracts hypersensitivity, neuroinflammation, and tissue damage in a mouse model of bortezomib-induced peripheral neuropathy.

Background: Neuropathy is a dose-limiting side effect of many chemotherapeutics, including bortezomib. The mechanisms underlying this condition are not fully elucidated even if a contribution of neuroinflammation was suggested. Here, we investigated the role of a chemokine family, the prokineticins (PKs), in the development of bortezomib-induced peripheral neuropathy (BIPN), and we used a PK receptor antagonist to counteract the development and progression of the pathology.

Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview.

Unlike fever, which is often over-treated especially in children, pain is underestimated and under-treated in pediatric age. The pharmacological agents approved for treating pain in these patients are few, also considering the recent limitation for codeine in children younger than 12 years. Paracetamol and the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen are the most used at this purpose.

Intra-Articular Cytokine Levels in Adolescent Patients after Anterior Cruciate Ligament Tear.

The treatment of anterior cruciate ligament (ACL) injuries in children and adolescents is challenging. Preclinical and clinical studies investigated ACL repairing techniques in skeletally immature subjects. However, intra-articular bioenvironment following ACL tear has not yet been defined in skeletally immature patients.

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.