23 research outputs found
Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation
BACKGROUND:
It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams.
OBJECTIVES:
To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases.
METHODS:
A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions.
RESULTS:
The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache.
CONCLUSIONS:
Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape
What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation
Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy
glo-3, a Novel Caenorhabditis elegans Gene, Is Required for Lysosome-Related Organelle Biogenesis
Gut granules are specialized lysosome-related organelles that act as sites of fat storage in Caenorhabditis elegans intestinal cells. We identified mutations in a gene, glo-3, that functions in the formation of embryonic gut granules. Some glo-3(−) alleles displayed a complete loss of embryonic gut granules, while other glo-3(−) alleles had reduced numbers of gut granules. A subset of glo-3 alleles led to mislocalization of gut granule contents into the intestinal lumen, consistent with a defect in intracellular trafficking. glo-3(−) embryos lacking gut granules developed into adults containing gut granules, indicating that glo-3(+) function may be differentially required during development. We find that glo-3(+) acts in parallel with or downstream of the AP-3 complex and the PGP-2 ABC transporter in gut granule biogenesis. glo-3 encodes a predicted membrane-associated protein that lacks obvious sequence homologs outside of nematodes. glo-3 expression initiates in embryonic intestinal precursors and persists almost exclusively in intestinal cells through adulthood. GLO-3∷GFP localizes to the gut granule membrane, suggesting it could play a direct role in the trafficking events at the gut granule. smg-1(−) suppression of glo-3(−) nonsense alleles indicates that the C-terminal half of GLO-3, predicted to be present in the cytoplasm, is not necessary for gut granule formation. Our studies identify GLO-3 as a novel player in the formation of lysosome-related organelles
Self-encapsulating Poly(lactic-<i>co</i>-glycolic acid) (PLGA) Microspheres for Intranasal Vaccine Delivery
Herein
we describe a formulation of self-encapsulating polyÂ(lactic-<i>co</i>-glycolic acid) (PLGA) microspheres for vaccine delivery.
Self-healing encapsulation is a novel encapsulation method developed
by our group that enables the aqueous loading of large molecules into
premade PLGA microspheres. Calcium phosphate (CaHPO<sub>4</sub>) adjuvant
gel was incorporated into the microspheres as a protein-trapping agent
for improved encapsulation of antigen. Microspheres were found to
have a median size of 7.05 ± 0.31 μm, with a w/w loading
of 0.60 ± 0.05% of ovalbumin (OVA) model antigen. The formulation
demonstrated continuous release of OVA over a 49-day period. Released
OVA maintained its antigenicity over the measured period of >21
days
of release. C57BL/6 mice were immunized via the intranasal route with
prime and booster doses of OVA (10 μg) loaded into microspheres
or coadministered with cholera toxin B (CTB), the gold standard of
mucosal adjuvants. Microspheres generated a Th2-type response in both
serum and local mucosa, with IgG antibody responses approaching those
generated by CTB. The results suggest that this formulation of self-encapsulating
microspheres shows promise for further study as a vaccine delivery
system
Formulation and Characterization of Nanoemulsion Intranasal Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity
The development of effective intranasal
vaccines is of great interest
due to their potential to induce both mucosal and systemic immunity.
Here we produced oil-in-water nanoemulsion (NE) formulations containing
various cationic and nonionic surfactants for use as adjuvants for
the intranasal delivery of vaccine antigens. NE induced immunogenicity
and antigen delivery are believed to be facilitated through initial
contact interactions between the NE droplet and mucosal surfaces which
promote prolonged residence of the vaccine at the site of application,
and thus cellular uptake. However, the details of this mechanism have
yet to be fully characterized experimentally. We have studied the
physicochemical properties of the NE droplet surfactant components
and demonstrate that properties such as charge and polar headgroup
geometry influence the association of the adjuvant with the mucus
protein, mucin. Association of NE droplets with mucin <i>in vitro</i> was characterized by various biophysical and imaging methods including
dynamic light scattering (DLS), zeta potential (ZP), and surface plasmon
resonance (SPR) measurements as well as transmission electron microscopy
(TEM). Emulsion surfactant compositions were varied in a systematic
manner to evaluate the effects of hydrophobicity and polar group charge/size
on the NE–mucin interaction. Several cationic NE formulations
were found to facilitate cellular uptake of the model antigen, ovalbumin
(OVA), in a nasal epithelial cell line. Furthermore, fluorescent images
of tissue sections from mice intranasally immunized with the same
NEs containing green fluorescent protein (GFP) antigen demonstrated
that these NEs also enhanced mucosal layer penetration and cellular
uptake of antigen <i>in vivo</i>. NE–mucin interactions
observed through biophysical measurements corresponded with the ability
of the NE to enhance cellular uptake. Formulations that enhanced antigen
uptake <i>in vitro</i> and <i>in vivo</i> also
led to the induction of a more consistent antigen specific immune
response in mice immunized with NEs containing OVA, linking NE-facilitated
mucosal layer penetration and cellular uptake to enhancement of the
immune response. These findings suggest that biophysical measurement
of the mucoadhesive properties of emulsion based vaccines constitutes
an effective <i>in vitro</i> strategy for selecting NE candidates
for further evaluation <i>in vivo</i> as mucosal adjuvants
Nanoemulsion is an effective antimicrobial for methicillin-resistant Staphylococcus aureus
Formulation, high throughput in vitro screening and in vivo functional characterization of nanoemulsion-based intranasal vaccine adjuvants.
Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity) and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17) could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications