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Chronic pain is highly prevalent in older adults and is associated with poor functional outcomes. Further, opioid analgesics are commonly utilized for the treatment of pain in older adults despite well-described adverse effects. Importantly, both chronic pain and opioid analgesics have been linked with impairments in cognitive function, though data are limited. In this manuscript we summarize the evidence and critical knowledge gaps regarding the relationships between pain, opioid analgesics, and cognition in older adults. Further, we provide a conceptual framework to guide future research in the development, implementation, and evaluation of strategies to optimize analgesic outcomes in older adults while minimizing deleterious effects on cognition.
Learn More >Headache disorders can produce recurrent, incapacitating pain. Migraine and cluster headache are notable for their ability to produce significant disability. The anatomy and physiology of headache disorders is fundamental to evolving treatment approaches and research priorities. Key concepts in headache mechanisms include activation and sensitization of trigeminovascular, brainstem, thalamic, and hypothalamic neurons; modulation of cortical brain regions; and activation of descending pain circuits. This review will examine the relevant anatomy of the trigeminal, brainstem, subcortical, and cortical brain regions and concepts related to the pathophysiology of migraine and cluster headache disorders.
Learn More >Endocannabinoids have an important role for the regulation of neuropathic pain. In our previous study, we observed that preventing the degradation of a endocannabinoid, 2-arachidonoylglycerol (2-AG), using an inhibitor of monoacylglycerol lipase (JZL184), attenuated neuropathic orofacial pain (NOP). The present study aimed to investigate mechanisms underlying JZL184-induced attenuation of NOP. We hypothesized that JZL184 may suppress microglial reactivity in the trigeminal spinal subnucleus caudalis (Vc) under NOP. The infraorbital nerve (ION) was hemisected to model NOP in mice, resulting in a significant reduction of mechanical head-withdrawal threshold (MHWT) on day 4 following the ION hemisection. Chronic systemic application of JZL184 at a concentration of 8 or 16 mg/kg/day for 4 days significantly attenuated the reduction of MHWT in mice exposed to NOP. Administering JZL184 at 4 mg/kg/day or its vehicle, however, did not attenuate the MHWT of mice with NOP. The reactivity of microglial cells in the Vc increased in mice with NOP compared to sham-operated controls. The application of JZL184 at 8 or 16 mg/kg/day for 4 days significantly reduced the increased microglial reactivity in the Vc. The changes of microglia under NOP were, by contrast, not reduced by application of the drug at 4 mg/kg/day or its vehicle. The results indicate that preventing 2-AG degradation may increase its accumulation in the Vc and normalize microglial reactivity under NOP, which may contribute to suppressing NOP.
Learn More >Central sensitisation contributes to patient variability when treating pain in endometriosis. Targeting this process may alleviate hyperalgesia and allodynia in women refractory to current treatments. Thus far, there has been no review of targeted treatments for central sensitisation in women with endometriosis. Therefore, this review aims to identify and summarise the findings of studies regarding the availability and efficacy of targeted treatments for central sensitisation in women with endometriosis.
Learn More >Posttraumatic headache (PTH) is the most common symptom following mild traumatic brain injury (mTBI) (also known as concussion). Migraine and PTH have similar phenotypes, and a migraine-like phenotype is common in PTH. The similarities between both headache types are intriguing and challenge a better understanding of the pathophysiological commonalities involved in migraine and PTH due to mTBI. Here, we review the PTH resting-state functional connectivity literature and compare it to migraine to assess overlap and differences in brain network function between both headache types. Migraine and PTH due to mTBI have overlapping and disease-specific widespread alterations of static and dynamic functional networks involved in pain processing as well as dysfunctional network connections between frontal regions and areas of pain modulation and pain inhibition. Although the PTH functional network literature is still limited, there is some evidence that dysregulation of the top-down pain control system underlies both migraine and PTH. However, disease-specific differences in the functional circuitry are observed as well, which may reflect unique differences in brain architecture and pathophysiology underlying both headache disorders.
Learn More >Opioid overdose rates continue to increase, and extant literature suggests that many individuals who use heroin were first introduced to opioids through a medical prescription.
Learn More >Bupivacaine hydrochloride (BVC) represents an option to produce long-lasting analgesia, and complexation in cyclodextrins has shown improvements in biopharmaceutical properties. This study aimed to characterize and test the cytotoxicity and antinociceptive effects of BVC complexed in sulfobutylether-β-cyclodextrin (SBEβCD). The kinetics and stoichiometry of complexation and BVC-SBEβCD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBEβCD complex formation was obtained from scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The cytotoxicity was evaluated in keratinocyte (HaCaT) and neuroblastoma (SH-SY5Y). Antinociceptive effects were registered via orofacial pain models: the formalin test, carrageenan-induced hyperalgesia, and postoperative pain (intraoral incision). The complex formation occurred at a 1:1 BVC-SBEβCD molar ratio, with a low association constant (13.2 M). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC values determined in SH-SY5Y were 216 µM and 149 µM for BVC and BVC-SBEβCD, respectively (p < 0.05). There was no difference in HaCaT IC. In orofacial pain model, BVC-SBEβCD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBEβCD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.
Learn More >The appropriate recognition and assessment of pain in animals is an essential tool that can be used by veterinary professionals, rehabilitators, household caregivers, and others to provide supportive care and analgesia to patients. Although the use of behavioral, postural, and facial changes to recognize pain have been studied in popular domestic species such as dogs (), cats (), and rabbits (), very little is known relative to avian species. The purpose of this article is to provide a literature review comprising structured searches on the topic of avian pain recognition. The emphasis of the searches were based on the behavioral and postural alterations that have thus far been explored. The literature review was performed in the months of August-September 2020 over 5 online databases: MEDLINE/ PubMed, CAB Direct, Biosis, Zoological Record, and Scopus. Additional "snowballing" was incorporated by looking at the references and articles that cited the 126 articles from the initial abstract and full-text screening. Of the 194 full-text articles reviewed, 132 sources of literature were included in the final analysis. From these 132 sources of literature, 31.8% were general review articles in which avian pain behaviors were described irrespective of species, with others being specific to a particular species (chickens 47.8%, turkeys 7.6%, parrots 3.8%, pigeons [] 3%, raptors 3%, and "other" 3%-2 on ducks, 1 on emus [], and 1 on Eurasian blue tits []). Pain stimulus varied depending on species, although the vast majority of the pain stimuli involved welfare issues such as beak trimming, limb abnormalities, and keel bone fractures in chickens. Although information regarding this topic remains limited for many avian species, this review provides a more thorough understanding of behavioral indicators of pain in species such as chickens, turkeys, psittacines, pigeons, raptors, and select others. It is the hope that this review will motivate further interest and future analgesia research for the improvement of avian welfare.
Learn More >The COVID-19 pandemic resulted in a novel challenge for healthcare delivery and implementation in the United States (US) in 2020 and beyond. Telemedicine arose as a significant and effective medium for safe and efficacious physician-patient interactions. Prior to the COVID-19 pandemic, telemedicine while available, had infrequently been utilized in pain medicine practices due to difficulties with reimbursement, the learning curve associated with new technology usage, and the need for new logistical systems in place to implement telemedicine effectively. Given the unique constraints on the healthcare system during the COVID-19 pandemic, the ubiquitous utilization of telemedicine among pain medicine physicians increased, giving insight into potential future roles for the technology beyond the pandemic.
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