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This systematic review synthesized evidence about the relationship between childhood bullying victimization and chronic pain, with a focus on the temporal nature of the relationship and moderating factors, such as the type and intensity of victimization.
Learn More >Pain management for cats with degenerative joint disease (DJD) remains a critical unmet need. Recent work has shown promise for a feline-specific anti-nerve growth factor monoclonal antibody (frunevetmab) to deliver safe and effective pain management. Our objectives were to evaluate the efficacy and safety of frunevetmab administered twice using two administration routes (subcutaneous and intravenous) compared to placebo. This was a randomized placebo-controlled, double-masked study. After a week-long pain and activity baseline, 126 cats were randomized to receive injections of frunevetmab (IV then SC; = 42 or SC then SC; = 43) or placebo (IV then SC; = 41) on Days 0 and 28. Owners completed questionnaires on Days 14, 28, 42, and 56. Accelerometry data were collected continuously throughout. Owner questionnaire results showed significant improvement in frunevetmab-treated cats [compared to placebo; ( < 0.05)] at Days 42 and 56; no difference was found between routes of administration for frunevetmab. All groups had decreased objectively measured weekly activity from baseline; frunevetmab-treated cats had a mean decrease of 0.9%, while placebo-treated cats had a mean decrease of 9.3%. Treatments were generally well-tolerated. The majority of adverse events included dermatitis/alopecia related to activity-monitor collars; these occurred in a higher percentage of frunevetmab, compared to placebo, treated cats. Treatment with frunevetmab provided improvements in owner ratings of mobility over treatment with placebo; these results were supported by objectively measured accelerometry. Frunevetmab has the potential to address a critical gap in the treatment of chronic pain in cats.
Learn More >Temporomandibular disorders (TMD) are a group of diseases in the oral and maxillofacial region that can manifest as acute or chronic persistent pain, affecting millions of people worldwide. Although hundreds of studies have explored mechanisms and treatments underlying TMD, multiple pathogenic factors and diverse clinical manifestations make it still poorly managed. Appropriate animal models are helpful to study the pathogenesis of TMD and explore effective treatment measures. At present, due to the high cost of obtaining large animals, rodents and rabbits are often used to prepare TMD animal models. Over the past decade, various animal models have been intensively developed to understand neurobiological and molecular mechanisms of TMD, and seek effective treatments. Although these models cannot carry out all clinical features, they are valuable in revealing the mechanisms of TMD and creating curative access. Currently, there are multitudinous animal models of TMD research. They can be constructed in different means and summarized into four ways according to the various causes and symptoms, including chemical induction (intra-articular injection of ovalbumin, collagenase, formalin, vascular endothelial growth factor, intramuscular injection of complete Freund's adjuvant, etc.), mechanical stress stimulation (passive mouth opening, change of chewing load), surgical operation (partial disc resection, joint disc perforation) and psychological stress induction. Here, we summarize and discuss different approaches of animal models for determining neurophysiological and mechanical mechanisms of TMD and assess their advantages and limitations, respectively.
Learn More >Early life surgery produces peripheral nociceptive activation, inflammation, and stress. Early life nociceptive input and inflammation have been shown to produce long-term processing changes that are not restricted to the dermatome of injury. Additionally stress has shown long-term effects on anxiety, depression, learning, and maladaptive behaviors including substance abuse disorder and we hypothesized that early life surgery would have long-term effects on theses complex behaviors in later life. In this study surgery in the rat hindpaw was performed to determine if there are long-term effects on anxiety, depression, audiovisual attention, and opioid reward behaviors. Male animals received paw incision surgery and anesthesia or anesthesia alone (sham) at postnatal day 6. At 10 weeks after surgery, open field center zone entries were decreased, a measure of anxiety ( = 20) ( = 0.03) (effect size, Cohen's = 0.80). No difference was found in the tail suspension test as a measure of depression. At 16-20 weeks, attentional performance in an operant task was similar between groups at baseline and decreased with audiovisual distraction in both groups ( < 0.001) (effect size, η = 0.25), but distraction revealed a persistent impairment in performance in the surgery group ( = 8) ( = 0.04) (effect size, η = 0.13). Opioid reward was measured using heroin self-administration at 16-24 weeks. Heroin intake increased over time in both groups during 24-h free access ( < 0.001), but was greater in the surgery group ( = 0.045), with a significant interaction between time and treatment ( < 0.001) (effect size, Cohen = 0.36). These results demonstrate long-term disruptions in complex behaviors from surgical incision under anesthesia. Future studies to explore sex differences in early life surgery and the attendant peripheral neuronal input, stress, and inflammation will be valuable to understand emerging learning deficits, anxiety, attentional dysfunction, and opioid reward and their mechanisms. This will be valuable to develop optimal approaches to mitigate the long-term effects of surgery in early life.
Learn More >Molecular and cellular interactions among spinal dorsal horn neurons and microglia, the resident macrophages of the central nervous system, contribute to the induction and maintenance of neuropathic pain after peripheral nerve injury. Emerging evidence also demonstrates that reciprocal interactions between macrophages and nociceptive sensory neurons in the dorsal root ganglion contribute to the initiation and persistence of nerve injury-induced mechanical hypersensitivity (allodynia). We previously reported that sensory neuron-derived colony-stimulating factor 1 (CSF1), by engaging the CSF1 receptor (CSF1R) that is expressed by both microglia and macrophages, triggers the nerve injury-induced expansion of both resident microglia in the spinal cord and macrophages in the dorsal root ganglion and induces their respective contributions to the neuropathic pain phenotype. Here, we review recent research and discuss unanswered questions regarding CSF1/CSF1R-mediated microglial and macrophage signaling in the generation of neuropathic pain.
Learn More >The α7 neuronal nicotinic acetylcholine receptors (α7nAChRs) are essential for anti-inflammatory responses. The human-specific CHRFAM7A gene and its 2bp deletion polymorphism (Δ2bp variant) encodes a structurally-deficient α7nAChRs that may impact the anti-inflammatory function. We studied 45 spinal cord injury (SCI) patients for up to six weeks post SCI to investigate the role of the Δ2bp variant on multiple circulating inflammatory mediators and two outcome measures (neuropathic pain and risk of pressure ulcers). The patient's SCI were classified as either severe or mild. Missing values were imputed. Overall genetic effect was conducted with independent sample t-test and corrected with false discovery rate (FDR). Univariate analysis and regression analysis were applied to evaluate the Δ2bp effects on temporal variation of inflammatory mediators post SCI and their interaction with outcome measures. In severe SCI, the Δ2bp carriers showed higher levels of circulating inflammatory mediators than the Δ2bp non-carriers in TNF-α (FDR = 9.6×10-4), IFN-γ (FDR = 1.3×10-3), IL-13 (FDR = 1.6×10-3), CCL11 (FDR = 2.1×10-3), IL-12p70 (FDR = 2.2×10-3), IL-8 (FDR = 2.2×10-3), CXCL10 (FDR = 3.1×10-3), CCL4 (FDR = 5.7×10-3), IL-12p40 (FDR = 7.1×10-3), IL-1b (FDR = 0.014), IL-15 (FDR = 0.024), and IL-2 (FDR = 0.037). IL-8 and CCL2 were negatively associated with days post injury (DPI) for the Δ2bp carriers (P = 2×10-7 and P = 2×10-8, respectively) and IL-5 was positively associated with DPI for the Δ2bp non-carriers (P = 0.015). Neuropathic pain was marginally positively associated with IL-13 for the Δ2bp carriers (P = 0.056). In mild SCI, the Δ2bp carriers had lower circulating levels of IL-15 (FDR = 0.04) than the Δ2bp non-carriers. Temporal variation of inflammatory mediators post SCI was not associated with the Δ2bp variant. For the mild SCI Δ2bp carriers, risk of pressure ulcers was positively associated with circulating levels of IFN-γ, CXCL10, and CCL4 and negatively associated with circulating levels of IL-12p70. These findings support an important role for the human-specific CHRFAM7A Δ2bp gene variant in modifying anti-inflammatory function of α7nAChRs following SCI.
Learn More >The majority of previous research that has examined the validity of pain intensity rating scales has been conducted in western and developed countries. Research to evaluate the generalizability of previous findings in non-developed countries is necessary for identifying the scales that are most appropriate for use in international research.
Learn More >Identifying pain-related response patterns and understanding functional mechanisms of symptom formation and recovery are important for improving treatment.
Learn More >Nonsteroidal anti-inflammatory drugs are widely used for migraine, but gastrointestinal tolerability limits use. We previously reported results from the first treatment period of this 2-period, randomized, controlled study comparing DFN-15-an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib-with placebo for the acute treatment of a moderate-severe migraine attack. Herein, we report the effects of treatment for the second treatment period.
Learn More >Fibromyalgia (FM) is a debilitating chronic pain condition with few treatment options. Central sensitization and neuroinflammation have been forwarded as models of FM pathophysiology, both of which indicate dextromethorphan (DXM) as a potential treatment. DXM is an NMDA-receptor antagonist and microglial modulator with anti-neuroinflammatory properties at low doses. It is available for clinical use but has not been tested as a treatment for FM at low dosages. This study evaluated the effectiveness of DXM in treating FM-associated symptoms.
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