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The antinociceptive effect of methadone in the morphine-resistant inflammatory pain state was described in the paw-withdrawal test using the complete Freund's adjuvant (CFA)-induced mouse inflammatory pain model. After intraplantar (i.pl.) injection of CFA, thermal hyperalgesia was observed in the ipsilateral paw. The antinociceptive effects of subcutaneous (s.c.) injection of morphine, fentanyl, and oxycodone against thermal hyperalgesia in the inflammatory pain state were reduced in the ipsilateral paw 7 days after CFA pretreatment. On the contrary, the antinociceptive effect of s.c. injection of methadone was maintained in the ipsilateral paw 7 days after CFA pretreatment. The suppressed morphine antinociception in the CFA model mice was bilaterally restored following s.c. treatment with methadone 20 min prior to or 3 days after CFA pretreatment. The suppressed morphine antinociception was also bilaterally restored by intraperitoneal treatment with MK-801 30 min prior to CFA pretreatment; however, the s.c. injection of morphine 30 min prior to CFA pretreatment failed to restore the suppressed morphine antinociception in the CFA model mice. The expression level of mRNA for µ-opioid receptors 7 days after i.pl. pretreatment was not significantly changed by i.pl. pretreatment with CFA or s.c. pretreatment with methadone. In conclusion, methadone is extremely effective against thermal hyperalgesia in the morphine-resistant inflammatory pain state, and restores suppressed morphine antinociception in the inflammatory pain state without altering the expression level of mRNA for µ-opioid receptors.
Learn More >The presence of a temporomandibular disorder is one of the most frequent causes of orofacial pain (OFP). When pain continues beyond tissue healing time, it becomes chronic and may be caused, among other factors, by the sensitization of higher-order neurons. The aim of this study is to describe psychological characteristics of patients with chronic OFP, their peripheral pain threshold, and electroencephalography (EEG) recording, looking for possible signs of central sensitization (CS). Twenty-four subjects with chronic OFP caused by temporomandibular disorder were evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders Axis I and Axis II. Pain intensity, catastrophizing, and presence of CS were assessed through self-reported questionnaires. Pressure pain threshold (PPT) was recorded in facial and peripheral sites; EEG activity was recorded during open and closed eyes resting state and also during the pain threshold assessment. Pain thresholds and EEG recordings were compared with a cohort of pain-free age- and sex-matched healthy subjects. Patients with chronic OFP showed a significant reduction in their pain threshold compared to healthy subjects in all sites assessed. Greater reduction in pain threshold was recorded in patients with more severe psychological symptoms. Decreased alpha and increased gamma activity was recorded in central and frontal regions of all subjects, although no significant differences were observed between groups. A general reduction in PPT was recorded in people who suffer from chronic OFP. This result may be explained by sensitization of the central nervous system due to chronic pain conditions. Abnormal EEG activity was recorded during painful stimulation compared to the relaxed condition in both chronic OFP subjects and healthy controls.
Learn More >Interdisciplinary multimodal pain therapy (IMPT) programs for chronic back pain are effective and recommended. The patient-centered and biopsychosocial nature of IMPT is grounded in contemporary understanding that chronic pain states reflect heightened sensitization of the nervous system rather than an issue in the tissue. Teaching patients about pain is part of IMPT programs, though a clinical guideline is lacking. This study aims to answer the following question: Does the addition of an evidence-based pain neuroscience education (PNE) lecture for patients, into an IMPT program, produce superior results than the IMPT program itself?
Learn More >Oliceridine, an investigational IV opioid, is a first-in-class G-protein selective agonist at the -opioid receptor. The G-protein selectivity results in potent analgesia with less recruitment of -arrestin, a signaling pathway associated with opioid-related adverse events (ORAEs). In randomized controlled studies in both hard and soft tissue models yielding surgical pain, oliceridine provided effective analgesia with a potential for an improved safety and tolerability profile at equianalgesic doses to morphine. The phase 3, open-label, single-arm, multicenter ATHENA trial demonstrated the safety, tolerability, and effectiveness of oliceridine in moderate to severe acute pain in a broad range of patients undergoing surgery or with painful medical conditions warranting use of an IV opioid. This retrospective, observational chart review study compared respiratory depression events associated with oliceridine administration as found in the ATHENA trial to a control cohort treated with conventional opioids.
Learn More >Scopus is a leading bibliometric database. It contains the largest number of articles cited in peer-reviewed publications The journals included in Scopus are periodically re-evaluated to ensure they meet indexing criteria and some journals might be discontinued for publication concerns. These journals remain indexed and can be cited. Their metrics have yet to be studied. This study aimed to evaluate the main features and metrics of journals discontinued from Scopus for publication concerns, before and after their discontinuation, and to determine the extent of predatory journals among the discontinued journals. We surveyed the list of discontinued journals from Scopus (July 2019). Data regarding metrics, citations and indexing were extracted from Scopus or other scientific databases, for the journals discontinued for publication concerns. A total of 317 journals were evaluated. Ninety-three percent of the journals (294/318) declared they published using an Open Access model. The subject areas with the greatest number of discontinued journals were (52/317; 16%), (34/317; 11%), and (31/317; 10%). The mean number of citations per year after discontinuation was significantly higher than before (median of difference 64 citations, p<0.0001), and so was the number of citations per document (median of difference 0.4 citations, p<0.0001). Twenty-two percent (72/317) were included in the Cabell's blacklist. The DOAJ currently included only 9 journals while 61 were previously included and discontinued, most for 'suspected editorial misconduct by the publisher'. The citation count of journals discontinued for publication concerns increases despite discontinuation and predatory behaviors seemed common. This paradoxical trend can inflate scholars' metrics prompting artificial career advancements, bonus systems and promotion. Countermeasures should be taken urgently to ensure the reliability of Scopus metrics both at the journal- and author-level for the purpose of scientific assessment of scholarly publishing.
Learn More >Altered Gut Microbiota Composition Is Associated With Back Pain in Overweight and Obese Individuals.
Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with ( = 14) or without ( = 22) back pain. Individuals with back pain had a higher abundance of the genera ( = 0.0008; FDR = 0.027) ( = 0.0098; FDR = 0.17), and ( = 0.02; FDR = 0.27) than those without back pain. abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. was positively correlated with BMI (rho = 0.35, = 0.03), serum adipsin (rho = 0.33, = 0.047), and serum leptin (rho = 0.38, = 0.02). Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering abundance to treat back pain.
Learn More >The G protein-gated inwardly rectifying K+ (GIRK) channels play important signaling roles in the central and peripheral nervous systems. However, the role of GIRK channel activation in pain signaling remains unknown mainly due to the lack of potent and selective GIRK channel activators until recently. The present study was designed to determine the effects and mechanisms of ML297, a selective GIRK1/2 activator, on nociception in the spinal cord by using behavioral studies and whole-cell patch-clamp recordings from substantia gelatinosa (SG) neurons. Rats were prepared for chronic lumber catheterization and intrathecal administration of ML297. The nociceptive flexion reflex was tested using an analgesy-meter, and the influence on motor performance was assessed using an accelerating rotarod. We also investigated pre- and post-synaptic actions of ML297 in spinal cord preparations by whole-cell patch-clamp recordings. Intrathecal administration of ML297 increased the mechanical nociceptive threshold without impairing motor function. In voltage-clamp mode of patch-clamp recordings, bath application of ML297 induced outward currents in a dose-dependent manner. The ML297-induced currents demonstrated specific equilibrium potential like other families of potassium channels. At high concentration, ML297 depressed miniature excitatory postsynaptic currents (mEPSCs) but not their amplitude. The ML297-induced outward currents and suppression of mEPSCs were not inhibited by naloxone, a μ-opioid receptor antagonist. These results demonstrated that intrathecal ML297 showed the antinociceptive effect, which was mediated through direct activation of pre- and post-synaptic GIRK channels. Selective GIRK channel activation is a promising strategy for the development of new agents against chronic pain and opioid tolerance.
Learn More >Although the evidence for attentional bias to pain-related information among individuals with chronic pain has been well established, there are a number of inconsistencies in the research that have been observed due to sample characteristics. Therefore, the present study expanded upon previous studies by including patients with a variety of chronic pain conditions and compared a chronic pain patient sample with healthy community sample. We also investigated how pain catastrophizing and other psychological factors in chronic pain patients affected attentional patterns to pain-related information. Forty chronic pain patients from the departments of neurology and rheumatology of an academic medical center hospital and 40 participants without chronic pain from a university that is located in Seoul, South Korea were recruited for the present study. Patients observed pictures of faces displaying pain that were presented simultaneously with faces with neutral expressions, while their eye movements were measured using an eye-tracking system. Independent -tests were conducted to investigate attentional preferences to pain stimuli between the chronic pain and control groups. No significant attentional differences in pain-neutral pairs were found for both chronic pain and control group. A one-way MANOVA was conducted to examine the role of pain catastrophizing on psychological factors and attentional engagement to pain stimuli. No significant results for the attentional bias to pain stimuli among chronic pain patients may indicate that chronic pain patients who have suffered from chronic pain for a long time and have been treated for their chronic pain in the hospital may interpret pain-related information not as threatening. Clinical implications related to use in pain treatment and future research suggestions are discussed.
Learn More >Current recommendations controversially discuss local infiltration techniques as specific treatment for refractory pain syndromes. Evidence of effectiveness remains inconclusive and local infiltration series are discussed as a therapeutic option in patients not responding to standard therapy. The aim of this study was to investigate the effectiveness of infiltration series with techniques such as sphenopalatine ganglion (SPG) block and ganglionic local opioid analgesia (GLOA) for the treatment of neuropathic pain in the head and neck area in a selected patient group.
Learn More >The involvement of calcitonin gene-related peptide in migraine and cluster headache has led to the recent development of new therapies. Galcanezumab, a novel monoclonal antibody targeting the calcitonin gene-related peptide, is approved for the migraine prevention and has recently been tested for the prevention of cluster headache. Two clinical trials have been conducted to investigate the efficacy and safety of galcanezumab in episodic cluster headache and chronic cluster headache. While efficacy endpoints were not met in the chronic subtype, galcanezumab reduced the weekly frequency of attacks in patients with episodic cluster headaches. In both studies, the antibody was well tolerated. This review summarizes and critically reviews the available data regarding the rationale behind targeting the calcitonin gene-related peptide with galcanezumab for the prevention of cluster headache.
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