Nervous system delivery of antilysophosphatidic acid antibody by nasal application attenuates mechanical allodynia after traumatic brain injury in rats

Abstract AbstractLysophosphatidic acid (LPA) is a bioactive lipid that impacts neurological outcomes after neurotrauma by inhibiting neuroregeneration, promoting inflammation, and contributing to behavioral deficits. Blocking LPA signaling with a novel anti-LPA monoclonal antibody (mAb) is neuroprotective after traumatic brain injury (TBI) if given to injured animals whose blood–brain barrier (BBB) has been compromised. It is hypothesized that the anti-LPA mAb could improve chronic pain initiated by TBI. However, poor brain penetration after systemic application of the antibody makes access to the central nervous system (CNS) problematic in situations where the BBB is intact. Our experiments investigated whether intranasal delivery of the anti-LPA mAb could bypass the BBB, allowing for direct entry of the antibody to certain areas of the CNS. When the humanized anti-LPA mAb, LT3114, was intranasally applied to injured rats within 30 minutes after mild TBI using the central lateral percussion model, enzyme-linked immunospecific assay and immunohistochemistry demonstrated antibody uptake to several areas in the CNS, including the area of cortical injury, the corpus callosum, cerebellum, and the subventricular region. Compared with control rats that received LT3114 but no TBI, TBI rats demonstrated significantly higher concentrations of intranasally administered LT3114 antibody in some tissues. In behavioral studies, a significant attenuation of mechanical allodynia after ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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CONCLUSION: SO remains a threatening clinical diagnosis that poses diagnostic and therapeutic challenges. It can be triggered post-traumatic, but also any intraocular surgery. This should be taken into account when assessing the indication for intraocular eye surgery, especially in eyes with reduced visual outcome. PMID: 32967030 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
CONCLUSIONS: Our study showed that Cernilen-flogo® treatment after PVP is effective and minimize patient's pelvic discomfort showed by lower VAS level resulting in better postoperatively patient's quality of life (QOL). PMID: 32965002 [PubMed - as supplied by publisher]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
AbstractChronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunologic...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Diseases and disorders such as Parkinson disease, schizophrenia, and chronic pain are characterized by altered mesolimbic dopaminergic neurotransmission. Dopamine release in the nucleus accumbens influences behavior through both tonic and phasic signaling. Tonic dopamine levels are hypothesized to inversely regulate phasic signals through dopamine D2 receptor feedback inhibition. We tested this hypothesis directly in the context of ongoing pain. Tonic and phasic dopamine signals were measured using fast-scan controlled-adsorption voltammetry and fast-scan cyclic voltammetry, respectively, in the nucleus accumbens shell of ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Chronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive, and emotional information and in conditioned pain modulation. We previously reported widespread epigenetic reprogramming in the PFC many months after nerve injury in rodents. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation at the onset of acute pain or how it progresses as pain transitions ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
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Source: Pain - Category: Anesthesiology Tags: Commentary Source Type: research
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Source: Pain - Category: Anesthesiology Tags: Topical Review Source Type: research
This study used eye-gaze tracking to examine attentional biases to pain-related stimuli in a clinical sample of youth with chronic pain and pain-free controls. The moderating role of attentional control was also examined. Youth with chronic pain (n = 102) and pain-free controls (n = 53) viewed images of children depicting varying levels of pain expressiveness paired with neutral faces while their eye gaze was recorded. Attentional control was assessed using both a questionnaire and a behavioural task. Both groups were more likely to first fixate on high pain faces but showed no such orienting bias for moderate or low pain ...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Classical Ehlers–Danlos syndrome (cEDS) is a connective tissue disorder caused by heterozygous mutations in one of the type V collagen-encoding genes, COL5A1 or COL5A2. cEDS is characterized by generalized joint hypermobility and instability, hyperextensible, fragile skin, and delayed wound healing. Chronic pain is a major problem in cEDS patients, but the underlying mechanisms are largely unknown, and studies in animal models are lacking. Therefore, we assessed pain-related behaviors in haploinsufficient Col5a1+/− mice, which clinically mimic human cEDS. Compared to wild-type (WT) littermates, 15 to 20-week-ol...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
This study evaluated the relative efficacy of 4 treatment sessions each of 4 nonpharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive 4 sessions of 1 of the 4 treatments. Primary (pain intensity) and secondary outcome measures were administered by assessors unaware of treatment allocation at pretreatment, posttreatment, and 3-, 6-, and 12-month follow-up. Treatment effects were evaluated u...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
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