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The "nociplastic pain," a recently proposed novel mechanistic pain descriptor, is defined as pain occurring through altered nociception without nociceptor activation and nerve injury. Nociplastic pain is often characterized by widespread pain sensitization (WSP) in multiple body regions (Fitzcharles et al., 2021). As many patients with primary chronic pain would have nociplastic backgrounds, developing appropriate methods to evaluate drug effects against nociplastic pain in animal model is in great demand. Using two rat models with the WSP involving central amygdala (CeA) activation by orofacial inflammation or direct chemogenetic activation (Sugimoto et al., 2021), we examined whether widely used analgesics, acetaminophen (AcAph), pregabalin (PGB), and duloxetine (DLX) could attenuate the WSP. AcAph (100 or 200 mg/kg, i.p.) significantly elevated 50%-paw withdrawal threshold (PWT), which had been lowered significantly by upper lip injection of formalin, or systemic injection of clozapine-N-oxide in the rats with excitatory designer receptors (hM3Dq) expressed in the right CeA. This effect lasted for > ∼4 h. PGB (30 mg/kg, i.p.) also significantly counteracted the lowered PWT in rats with orofacial formalin injection for >∼6 h. DLX was ineffective on the WSP. Based on these results, we propose that these preclinical models could be used to evaluate drug effects for primary chronic pain. We conclude that the widely used pain killers, AcAph and PGB, also relieve nociplastic widespread sensitization in the absence of ongoing nociceptor activation and nerve injury.
Learn More >Botulinum toxin type A (BTX-A) is a recently developed treatment for the management of peripheral neuropathic pain. The objective of this study was to provide a synthesis of the evidence concerning the efficacy and safety of subcutaneous botulinum toxin type A injections.
Learn More >Axial Spondyloarthritis is a rheumatic condition affecting young patients with social and occupational consequences. Diagnosis delay is associated with functional impairment and impact on quality of life, requiring a multidisciplinary approach.
Learn More >Bladder pain syndrome/interstitial cystitis (BPS/IC) is a refractory disease accompanied by bladder-related pain and hyperactivity. Studies have shown that the translocator protein (TSPO) modulates neuroinflammation and central sensitisation associated with pain. Moreover, we previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates neuroinflammation and mechanical allodynia in cyclophosphamide (CYP)-induced cystitis through activation of glial cells. Here, we aimed to explore whether activation of TSPO attenuates mechanical allodynia and bladder dysfunction by regulating BDNF induced neuroinflammation in a CYP-induced cystitis model.
Learn More >Chronic non-cancer pain in children and adolescents can be impairing and results in substantial health care costs. Intensive Interdisciplinary Pain Treatment (IIPT), an inpatient or day hospital treatment delivered by a team of three or more health professionals, may be an effective intervention for these children and adolescents. Based on previous reviews and meta-analyses, we updated the findings regarding the description of available treatments and estimated the effectiveness of IIPT, overcoming methodological shortcomings of previous work by requesting and analyzing individual participant data. On June 26, 2021, we searched five literature databases (PubMed, PsycINFO, Web of Science, Cochrane Library, and PubPsych) for studies examining the effectiveness of IIPT. Included studies employed a pre-post design, assessed patients under the age of 22 years, and presented their results in English, German, French, or Spanish. We used standard methodological procedures expected by Cochrane to pool treatment effects and assess risk of bias. We identified 13 different treatment sites with similar treatment inclusion criteria and treatment components, but the descriptions of those treatments varied widely. Regarding treatment effectiveness, IIPT may result in large improvements in mean pain intensity (g=-1.28), disability (g=-1.91), and number of missed school days at 12-month follow-up (g=-0.99), as well as moderate improvements in anxiety (g=-0.77) and depression (g=-0.76). The certainty of the evidence, however, was graded very low to low. We recommend future researchers employ more scientific rigor to increase the certainty of the evidence for IIPT and to standardize treatment outcomes for children and adolescents with chronic pain.
Learn More >Neuropathic pain is an unbearable condition caused by nervous system damage. As distinct acute pain, neuropathic pain is chronic, and it severely influences quality of life. N,N-Dimethyl-d-erythro-sphingosine (DMS), a neuropathic pain inducer, is metabolited de novo from sphingosine. In a recent study, metabolomics showed an increased concentration level of DMS in the spinal cord in mice with neuropathic pain. Nerve growth factor (NGF) is one of the peripheral nervous system targeted pain factors that interact with tropomyosin receptor kinase A (trkA). On the basis of this information, we were interested in the possibility that DMS may induce neuropathic pain-like behavior through an increase of NGF activity. In this study, we showed that DMS can enhance the binding of NGF to trkA, followed by neurite outgrowth of epidermal nerve fibers and phosphorylation of trkA. In addition, a stereoisomer, N,N-dimethyl-l-erythro-sphingosine, did not any show such biological activities. The results suggest that DMS can enhance the binding of NGF to trkA and that its stereochemistry is an essential factor for exhibiting its activity.
Learn More >Interventions to reduce harms related to prescription opioids are needed in primary care settings.
Learn More >Implanted and transcutaneous nerve stimulators have shown promise as novel non-pharmacologic treatment for episodic and chronic migraines. The purpose of this study was to summarize the reported efficacy of transcutaneous single nerve stimulators in management of migraine frequency and severity.
Learn More >Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that is characterized by abdominal pain and an altered defecation pattern. It affects between 5 and 20% of the general population and can seriously impact quality of life. The pathophysiology of IBS is rather complex and multifactorial including, for example, altered signalling by the gut-brain axis, dysbiosis, abnormal visceral pain signalling and intestinal immune activation. The latter has gained particular interest in recent years, with growing insight into the bidirectional communication between the nervous system and the immune system. In this Review, we detail the current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS and discuss the potential mechanisms involved. Moreover, we describe how immune mediators, particularly those released by mast cells, can directly activate or sensitize pain-transmitting nerves, leading to increased pain signalling and abdominal pain. Finally, we discuss the potential of interventions targeting immune activation as a new therapeutic strategy for patients suffering from IBS.
Learn More >The onset of both chronic pain and insomnia is high during adolescence. Although a bidirectional relationship between pain and insomnia has support, how pain and sleep co-develop throughout adolescence remains unknown. Sleep-wake patterns, pre-sleep behavior and pre-sleep arousal may influence the co-development of pain and insomnia. Four waves of longitudinal self-report data were used (N = 2767, Age M = 13.65 years, SD = 0.65). Multidimensional growth mixture modeling was used to identify four subgroups of adolescents with different concurrent trajectories of pain and insomnia. The trajectories followed each other across time in all classes: one class of consistently low pain and insomnia (68.7%), one class with persistent high symptoms (4.9%), as well as one class of increasing (13.9%), and one of decreasing (12.5%), trajectories. Later sleep-wake patterns and more pre-sleep cognitive-emotional arousal predicted both increasing and decreasing trajectories of concurrent pain and insomnia. The current study showed that developmental trajectories of pain and insomnia follow each other within adolescents and across adolescence. Both sleep-phase focused interventions as well as psychological interventions that focus on pre-sleep cognitive-emotional arousal may prove beneficial for adolescents with comorbid pain and insomnia.
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