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Although recent studies have shown that botulinum toxin-A (BTX-A) has a good analgesic effect on trigeminal neuralgia (TN) and peripheral neuropathic pain (PNP), the quality of evidence is low due to limited data. This meta-analysis is used to synthesize existing evidence for the treatment of these conditions with BTX-A.
Learn More >We have recently demonstrated that the neurosteroid-metabolizing enzyme, cytochrome P450c17 is increased in spinal astrocytes contributing to the development of mechanical allodynia in chronic constriction injury (CCI)-induced neuropathic mice. However, the mechanisms by which spinal P450c17 modulates pathological changes in astrocytes remain unclear. In this study we investigated whether P450c17 modulates astrocyte activation and whether this process is mediated by spinal p38 mitogen-activated protein kinase phosphorylation ultimately leading to the development of mechanical allodynia in CCI mice. Sciatic nerve injury induced a significant increase in glial fibrillary acidic protein (GFAP) expression in the superficial dorsal horn (SDH, laminae I-II) and nucleus proprius (NP, laminae III-IV) regions of the spinal cord dorsal horn. Repeated daily (from days 0-3 post-surgery) intrathecal administration of the P450c17 inhibitor, ketoconazole (10 nmol) significantly inhibited the CCI-induced increase in GFAP-immunoreactivity, but had no effect on the CCI-induced increase in Iba-1-immunoreactivity. In addition, intrathecal administration of ketoconazole significantly inhibited the CCI-induced increase in p38 phosphorylation, while the levels of ERK and JNK phosphorylation remained unchanged. The CCI-induced development of mechanical allodynia was attenuated by administration of either ketoconazole (10 nmol) or the p38 MAPK inhibitor, SB203580 (5 nmol). Administration of a sub-effective dose of SB203580 (0.5 nmol) potentiated the pharmacological effect of ketoconazole (1 nmol) on spinal GFAP-immunostaining, as well as, the development of mechanical allodynia following CCI. Collectively these data suggest that spinal P450c17 activates astrocytes via p38 phosphorylation, ultimately leading to the development of mechanical allodynia in a model of peripheral neuropathy.
Learn More >Gabapentinoid use has increased substantially in the past several years after initial promising data with regard to acute perioperative pain control. The purpose of this review is to critically appraise the evidence for the use of gabapentinoids for acute pain management and its impact on the development of chronic pain after surgery.
Learn More >Over half of youth with chronic pain report sleep deficiency including difficulties falling asleep, maintaining sleep, feeling unrested, and experiencing short sleep duration. Sleep deficiency has been shown to play a causal role in the development or worsening of chronic pain, and is associated with a variety of negative consequences for youth with chronic pain. The purpose of this review is to provide a summary of the literature on the interrelationship of sleep and chronic pain in adolescents. We review the impact and prevalence of sleep disturbances, conceptual models of the interrelationship of sleep and pain, biobehavioral mechanisms and risk factors, sleep assessment, and treatment of sleep deficiency and chronic pain in adolescents. Our recommendations for future research include understanding biobehavioral mechanisms that underlie the link between chronic pain and sleep deficiency to help guide development and testing of treatments for co-occurring pain and sleep disturbance in adolescents.
Learn More >Recent research has suggested that the magnitudes of analgesic treatment effects estimated in clinical trials have decreased over time. Implications of these findings for future sample size calculations and clinical trial research designs have not been addressed. In this article, we examine the standardized effect size (SES) for average pain intensity (API) and worst pain intensity (WPI) outcomes from randomized clinical trials (RCTs) of analgesic treatments shown to be efficacious for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia that were published between 1980 and 2016. API and WPI SESs have declined over time and are approximately 0.30 in the most recent trials. This is similar to the mean SESs found in recent RCTs of efficacious antidepressant medications for the treatment of depression. We propose that in many circumstances this value should be considered when conducting sample size determinations for phase 2 and 3 analgesic RCTs. Other methods to address the challenge of modest treatment effects by increasing trial efficiency and assay sensitivity are also briefly discussed. PERSPECTIVE: This article examines continuous pain intensity data obtained from analgesic treatment trials for chronic low back pain, fibromyalgia, osteoarthritis pain, painful diabetic peripheral neuropathy, and postherpetic neuralgia. Numerical declines in standardized effect sizes (SESs) were observed, with SESs being approximately 0.30 in the most recent trials.
Learn More >Itch was defined as "an unpleasant cutaneous sensation that provokes a desire to scratch" by Rothman in 1941. In mouse models, scratch bouts are typically counted to evaluate itch induced by pruritogens. However, previous reports have shown that algesic substances also induce scratching behaviors in a mouse neck injection model, which is the most common test used for scratching behaviors. This finding makes it difficult to study itch in mice. In contrast, capsaicin, a common algogen, reduced scratching behaviors in some neck injection experiments. Therefore, the effect of pain on scratching behaviors remains unclear. It is thus necessary to develop a method to concurrently investigate itch and pain sensation using behavioral tests. Here, a cheek injection model is introduced which can be used to simultaneously measure pain- and itch-related behaviors. In this model, pruritogens induce scratching behaviors while algesic substances induce wiping behaviors. Using this model, lysophosphatidic acid (LPA), an itch mediator found in cholestatic patients with itch, is shown to exclusively induce itch but not pain. However, in mouse models, LPA has been reported to be both a pruritogen and an algogen. Investigation into the effects of LPA in a mouse cheek injection model showed that LPA only induced scratching, but not wiping behaviors. This indicates that LPA acts as a pruritogen similarly in mice and humans, and demonstrates the utility of a cheek injection model for itch research.
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