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This longitudinal case-control study aims to 1) compare symptoms and functioning in otherwise healthy adolescents with versus without a parent with chronic pain (Parent CP+/Parent CP-) 2) test adolescent sex as a moderator of the relation between parent CP group and child functioning, and 3) determine changes in adolescent pain over one year. Adolescents (n=140; ages 11-15) completed tests of pain responsivity and physical function, as well as self-report measures assessing pain characteristics, somatic symptoms, and physical and psychosocial functioning. Self-reported pain and somatic symptoms were re-assessed one year later. Adolescents in the Parent CP+ group reported greater pain, somatic symptoms, and worse physical health than Parent CP- youth. Parent CP+ youth performed worse on all tests of physical function. Some observed effects were stronger for girls than boys. There were no differences between groups on pain responsivity. Both groups reported increased pain and somatic symptoms from baseline to one-year follow-up, with the Parent CP+ group reporting the highest level of symptoms at both time points. This study highlights the potential impact of parental pain status on children, particularly daughters, and is the first to document objective physical functioning differences in youth at risk for developing chronic pain. Perspective: Adolescents who have a parent with chronic pain demonstrate higher pain and lower physical function than adolescents who have a parent without chronic pain. Group differences in pain and somatic symptoms persist over one year. Family based interventions are needed for comprehensive pain prevention and treatment.
Learn More >Cisplatin is a widely used platinum-derived antineoplastic agent that frequently results in peripheral neuropathy. Therapeutic strategies for neuropathic pain are limited and characterized by variable efficacy and severe adverse effects. Clinical translation of novel analgesics has proven difficult with many agents demonstrating preclinical efficacy failing in clinical trials. Preclinical studies frequently assess pain behaviors in the hind paws, however the front paws have a greater degree of the fine sensorimotor functions characteristically damaged by chemotherapy-induced neuropathy. This is the first study to assess pain responses in the front paws. Here we test the hypothesis that mouse front paws exhibit pain-related alterations in mechanical and thermal (cold) sensitivity in a murine model of cisplatin-induced neuropathy, and that pharmacological treatment with amitriptyline, gabapentin, ibuprofen and URB937 normalize pain behaviors in the front and hind paws. Cold (acetone withdrawal latencies) and mechanical (von Frey withdrawal thresholds) sensitivity were significantly decreased and increased respectively in both the front and the hind paws following initiation of weekly systemic (intraperitoneal) cisplatin injections (5 mg/kg). For the hind paws, systemic administration of amitriptyline (30 mg/kg), gabapentin (100 mg/kg), ibuprofen (0 -10 mg/kg) or URB937 (0 -10 mg/kg) resulted in a decrease in acetone withdrawal latencies and increase in von Frey withdrawal thresholds with return to normal values at the highest doses tested. For the front paws, return to baseline values for the highest doses was found for cold allodynia but not mechanical allodynia, where the highest doses failed to return to baseline values. These results indicate that mouse front paws exhibit pain-related changes in cisplatin-induced neuropathy and that drug effects can vary based on testing stimulus and location. This suggests that front paw responses across multiple modalities provide reliable and accurate information about pain-related drug effects. Future studies should be aimed at elucidating the mechanisms underlying these differential effects.
Learn More >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.
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