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The combination of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) has been commonly used for inflammation and chronic articular pain in the clinic. Nonetheless, the long-term administration of both medications might result in osteonecrosis of the knee due to repeated injections of steroids and side effects in the gastrointestinal and cardiovascular systems. To overcome these unmet medical needs, we designed a microsphere-microcrystal-gel delivery system for intra-articular injection. Dexamethasone (DEX)-loaded microspheres (DMs) were optimized by Plackett-Burman and Taguchi orthogonal designs to extend their retention time in the knee joint. Celecoxib (CLX) microcrystals (CMs) were manufactured using an ultrasonic method to improve solubility and bioavailability. Moreover, a green solvent-free method was employed to crosslink and synthesize a novel poloxamer 407/Gantrez® S97-based gel system (GZF), which can undergo the sol-gel transition at lower concentrations. Then, DM and CM were loaded by GZF to form intra-articular injectable gels (DM/CM/Gel). The in vitro release of DEX and CLX showed a fast phase in 24 h followed by a controlled release of ∼8 d. Both blank microspheres and GZF gels displayed great biocompatibility against RAW264.7 macrophages. The most suitable dosages of 5 nM DEX and 125 nM CLX in the formulation were chosen because of their significant effects against macrophage inflammation with a lower administrative amount. An In vivo animal evaluation showed that DM/CM/Gel suppressed the release of inflammatory cytokines (TNF-α and IL-6) after 21 d of treatment. In addition, a histological evaluation revealed that DM/CM/Gel interrupted the progression of cartilage surface denudation and matrix loss. Therefore, DM/CM/Gel provides a prospective strategy for reforming traditional therapy for chronic articular disease.
Learn More >Second-order spinal cord excitatory neurons play a key role in spinal processing and transmission of pain signals to the brain. Exogenously-induced change in developmentally-imprinted excitatory neurotransmitter phenotype of these neurons to inhibitory has not yet been achieved. Here we use a subpial dorsal horn-targeted delivery of AAV (adeno-associated virus) vector(s) encoding GABA (gamma-Aminobutyric acid,) synthesizing-releasing inhibitory machinery in mice with neuropathic pain. Treated animals showed a progressive and complete reversal of neuropathic pain (tactile and brush-evoked pain behavior) which persisted for minimum 2.5 months post-treatment. The mechanism of this treatment effect results from the switch of excitatory to preferential inhibitory neurotransmitter phenotype in dorsal horn nociceptive neurons and a resulting increase in inhibitory activity in regional spinal circuitry after peripheral nociceptive stimulation. No detectable side effects (such as sedation, motor weakness or loss of normal sensation) were seen between 2-13 months post-treatment in naive adult mice, pigs and non-human primates. The use of this treatment approach may represent a potent and safe treatment modality in patients suffering from spinal cord- or peripheral nerve-injury induced neuropathic pain.
Learn More >Central neuropathic pain is caused by a disease or lesion of the brain or spinal cord. It is difficult to predict which patients will develop central pain syndromes after a central nervous system injury, but depending on the etiology, lifetime prevalence may be greater than 50%. The resulting pain is often highly distressing and difficult to treat, with no specific treatment guidelines currently available. This narrative review discusses mechanisms contributing to central neuropathic pain, and focuses on pharmacological approaches for managing common central neuropathic pain conditions such as central post-stroke pain, spinal cord injury-related pain, and multiple sclerosis-related neuropathic pain. Tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids have some evidence for efficacy in central neuropathic pain. Medications from other pharmacologic classes may also provide pain relief, but current evidence is limited. Certain non-pharmacologic approaches, neuromodulation in particular, may be helpful in refractory cases. Emerging data suggest that modulating the primary afferent input may open new horizons for the treatment of central neuropathic pain. For most patients, effective treatment will likely require a multimodal therapy approach.
Learn More >Chronic pain of various origin is known to be associated with selective cognitive impairment. Osteoarthritis (OA) of the hip is one of the leading causes of chronic pain in the adult population, but its association with cognitive performance has not been evaluated. Here, we investigate the effect of chronic pain due to unilateral OA of one hip and no further source of chronic pain on cognitive performance.
Learn More >This post-hoc analysis estimated annual indirect cost savings with galcanezumab (GMB) treatment in patients with episodic migraine (EM) or chronic migraine (CM).
Learn More >Heterogeneity among reported outcomes from enhanced recovery after cesarean delivery impact studies is high. This study aimed to develop a standardized enhanced recovery core outcome set for use in future enhanced recovery after cesarean delivery studies.
Learn More >Spasticity and chronic neuropathic pain are common and serious symptoms in people with multiple sclerosis (MS). These symptoms increase with disease progression and lead to worsening disability, impaired activities of daily living and quality of life. Anti-spasticity medications and analgesics are of limited benefit or poorly tolerated. Cannabinoids may reduce spasticity and pain in people with MS. Demand for symptomatic treatment with cannabinoids is high. A thorough understanding of the current body of evidence regarding benefits and harms of these drugs is required.
Learn More >Fibromyalgia (FM) is a chronic pain syndrome associated with fatigue, insomnia, dyscognition, and emotional distress. Critical illness mechanisms include central sensitization to nociceptive and non-nociceptive stimuli often resulting in hypersensitivity to all sensory input.
Learn More >The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA).
Learn More >The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009-2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3-6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain – a type of pain where the risk-benefit ratio of opioids is controversial.
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