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A growing pediatric and adult literature highlights the role of injustice appraisals in adjustment to pain. However, interpersonal injustice dynamics have remained largely unexplored. The present study investigated the factor structure and criterion validity of parentally-adjusted versions of the Injustice Experience Questionnaire, assessing child-oriented (IEQ-Pc) and self-oriented appraisals (IEQ-Ps) in the context of child pain. Participants were triads of healthy children (N=407, M=12) and both their parents and dyads of children with chronic pain (N=319, M=14) and one parent. In both samples, children completed measures of functional disability and quality of life (physical, emotional, social, academic); parents completed the IEQ-Pc, IEQ-Ps, and a measure of parental catastrophizing about child pain. Across samples, a confirmatory oblique two-factor model (Severity/Irreparability-Blame/Unfairness) provided a better fit to the data compared to a one-factor model; nevertheless, the two-factor solution was considered suboptimal. A post-hoc exploratory factor analysis consistently revealed one factor. In terms of criterion validity, the IEQ-Pc and IEQ-Ps demonstrated differential associations depending on the child's pain vs. healthy status, independent of parental catastrophizing. Further, findings in the healthy sample indicated that fathers' self-oriented injustice appraisals related to lower child social function. In the clinical sample, parental child-oriented injustice appraisals related to greater child functional disability and lower physical, emotional, social, and academic function. Current findings support the unique role of parental injustice appraisals, assessed by the IEQ-Pc and IEQ-Ps, in understanding child pain, but also suggest these may only partially capture the phenomenology of parental injustice appraisals in the context of child pain. PERSPECTIVE: This manuscript presents an examination of the construct and criterion validity of two parentally adjusted versions of the Injustice Experience Questionnaire. These measures could be valuable tools for clinicians in examining how parents respond to their child's pain as it impacts both the child's life as well as the parents'.
Learn More >Anecdotal evidence that cannabis preparations have medical benefits together with the discovery of the psychotropic plant cannabinoid Δ-tetrahydrocannabinol (THC) initiated efforts to develop cannabinoid-based therapeutics. These efforts have been marked by disappointment, especially in relation to the unwanted central effects that result from activation of cannabinoid receptor 1 (CB1), which have limited the therapeutic use of drugs that activate or inactivate this receptor. The discovery of CB2 and of endogenous cannabinoid receptor ligands (endocannabinoids) raised new possibilities for safe targeting of this endocannabinoid system. However, clinical success has been limited, complicated by the discovery of an expanded endocannabinoid system – known as the endocannabinoidome – that includes several mediators that are biochemically related to the endocannabinoids, and their receptors and metabolic enzymes. The approvals of nabiximols, a mixture of THC and the non-psychotropic cannabinoid cannabidiol, for the treatment of spasticity and neuropathic pain in multiple sclerosis, and of purified botanical cannabidiol for the treatment of otherwise untreatable forms of paediatric epilepsy, have brought the therapeutic use of cannabinoids and endocannabinoids in neurological diseases into the limelight. In this Review, we provide an overview of the endocannabinoid system and the endocannabinoidome before discussing their involvement in and clinical relevance to a variety of neurological disorders, including Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, stroke, epilepsy and glioblastoma.
Learn More >Voltage-dependent sodium and calcium channels in pain-initiating nociceptor neurons are attractive targets for new analgesics. We made a permanently charged cationic derivative of an N-type calcium channel-inhibitor. Unlike cationic derivatives of local anesthetic sodium channel blockers like QX-314, this cationic compound inhibited N-type calcium channels more effectively with extracellular than intracellular application. Surprisingly, the compound is also a highly effective sodium channel inhibitor when applied extracellularly, producing more potent inhibition than lidocaine or bupivacaine. The charged inhibitor produced potent and long-lasting analgesia in mouse models of incisional wound and inflammatory pain, inhibited release of the neuropeptide calcitonin gene-related peptide (CGRP) from dorsal root ganglion neurons, and reduced inflammation in a mouse model of allergic asthma, which has a strong neurogenic component. The results show that some cationic molecules applied extracellularly can powerfully inhibit both sodium channels and calcium channels, thereby blocking both nociceptor excitability and pro-inflammatory peptide release.
Learn More >Active research is being conducted on musculoskeletal pain, and recent concepts will help clinicians and researchers to develop better approaches: -the new pain taxonomy recently has been modified with a third descriptor with the concept of nociplastic pain. -the latest International Classification of Diseases (ICD-11) includes an IASP task force that developed a new classification system for pain. In this new classification, one can differentiate primary musculoskeletal pain including fibromyalgia and low back pain and secondary musculoskeletal pain related to specific etiologies. -the concept of central sensitization in inflammatory rheumatic diseases is increasingly discussed. In these conditions, even with very active biological treatment, almost a third of patients are still complaining of persisting pain. These persisting pain states under adequate treatment, without any sign of inflammation, led researchers to look for evidence of central sensitization states.
Learn More >Knee pain in osteoarthritis is complex and complicated by the fact that osteoarthritis is considered to be a disorder of multiple phenotypes. This complexity challenges our understanding as to why some people remain relatively symptom-free, while others progress to persistent pain. One approach to understanding the mechanisms underlying the transition to persistent pain is by identifying pain susceptibility phenotypes in people with or at risk of knee osteoarthritis. Using variables representative of the multidimensional nature of pain in people who were free of persistent pain, we identified four phenotypes characterised by low pressure pain thresholds and temporal summation and not psychosocial factors in those who developed persistent pain two years later. The group with the highest proportion of low pressure pain thresholds and a moderate proportion with facilitated temporal summation had twice the odds of developing persistent knee pain. This work provides preliminary insights into the critical importance of altered neurobiological mechanisms of pain signalling that contributes to development of chronic, persistent pain in knee osteoarthritis.
Learn More >Neural function depends on maintaining cellular membrane potentials as the basis for electrical signaling. Yet in mammals and insects, neuronal and glial membrane potentials can reversibly depolarize to zero, shutting down neural function by the process of spreading depolarization (SD) that collapses the ion gradients across membranes. SD is not evident in all metazoan taxa with centralized nervous systems. We consider the occurrence and similarities of SD in different animals and suggest that it is an emergent property of nervous systems that have evolved to control complex behaviours requiring energetically expensive, rapid information processing in a tightly regulated extracellular environment. Whether SD is beneficial or not in mammals remains an open question. However, in insects it is associated with the response to harsh environments and may provide an energetic advantage that improves the chances of survival. The remarkable similarity of SD in diverse taxa supports a model systems approach to understanding the mechanistic underpinning of human neuropathology associated with migraine, stroke and traumatic brain injury.
Learn More >Signaling mediated by soluble epoxide hydrolase (sEH) has been reported to play an important role in pain processing. Previous studies revealed that sEH activity is inhibited by specific binding of electrophiles to a redox-sensitive thiol (Cys521) adjacent to the catalytic center of the hydrolase. Here, we investigated if this redox-dependent modification of sEH is involved in pain processing using "redox-dead" knockin-mice (sEH-KI), in which the redox-sensitive cysteine is replaced by serine. However, behavioral characterization of sEH-KI mice in various animal models revealed that acute nociceptive, inflammatory, neuropathic, and visceral pain processing is not altered in sEH-KI mice. Thus, our results suggest that redox-dependent modifications of sEH are not critically involved in endogenous pain signaling in mice.
Learn More >Many patients use opioids chronically before surgery; it is unclear if surgery alters the likelihood of ongoing opioid consumption in these patients.
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