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In dementia, neuropathological changes alter the perception and expression of pain. For clinicians and family members, this knowledge gap leads to difficulties in recognizing and assessing chronic pain, which may consequently result in persons with dementia receiving lower levels of pain medication compared to those without cognitive impairment. Although this situation seems to have improved in recent years, considerable geographical variation persists. Over the last decade, opioid use has received global attention as a result of overuse and the risk of addiction, while the literature on older persons with dementia actually suggests undertreatment. This review stresses the importance of reliable assessment and the regular evaluation and monitoring of symptoms in persons with dementia. Based on current evidence, we concluded that chronic pain is still undertreated in dementia.
Learn More >Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.
Learn More >7β-(3-Ethyl–crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro–notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.
Learn More >Endometriosis is a chronic gynecological disorder characterized by the growth of endometrial glands and stroma outside the endometrial cavity producing inflammation and pain. Previously we demonstrated that modulation of the hypothalamic pituitary adrenal (HPA) axis exacerbates the development and severity of this condition. A physically active lifestyle has been shown to confer health benefits in many chronic conditions by potentially acting as a stress buffer, thus we hypothesized that voluntary physical exercise can 'realign/reset' the HPA axis resulting in reduced endometriosis symptoms in an animal model.
Learn More >Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses.
Learn More >Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed a systems pharmacology model of intracellular signaling in peripheral neurons to identify novel drug targets for preventing peripheral neuropathy associated with proteasome inhibitors. Model predictions suggested the combinatorial inhibition of TNFα, NMDA receptors, and reactive oxygen species should prevent proteasome inhibitor-induced neuronal apoptosis. Dexanabinol, an inhibitor of all three targets, partially restored bortezomib-induced reduction of proximal action potential amplitude and distal nerve conduction velocity and prevented bortezomib-induced mechanical allodynia and thermal hyperalgesia in rats, including a partial recovery of intraepidermal nerve fiber density. Dexanabinol failed to restore bortezomib-induced decreases in electrophysiological endpoints in rats, and it did not compromise bortezomib anti-cancer effects in U266 multiple myeloma cells and a murine xenograft model. Owing to its favorable safety profile in humans and preclinical efficacy, dexanabinol might represent a treatment option for bortezomib-induced neuropathic pain.
Learn More >Sedentariness is a substantial risk for many chronic diseases. We aimed to investigate the correlation of sedentary behavior and its indicators with low back pain (LBP) among adults and children. Original articles published up to April 28, 2020, using PubMed, Embase, Web of Science and Scopus were evaluated. Odds ratio (OR, 95% CI) was considered the overall effect size for desired associations. We reviewed 49 English articles with analytical observational study design, of which, 27 studies with cross sectional/survey design were retained in the meta-analysis. Among adults, sedentary lifestyle was a considerable risk factor for LBP (OR=1.24, 1.02-1.5); prolonged sitting time (OR=1.42, 1.09-1.85) and driving time (OR=2.03, 1.22-3.36) were the significant risk factors. Sedentary behavior was associated with LBP in office workers (OR=1.23). Moreover, excess weight (OR=1.35, 1.14-1.59) and smoking (OR=1.28, 1.03-1.60) were associated with LBP. Among children, sedentary lifestyle was a remarkable risk factor for LBP (OR=1.41, 1.24- 1.60); prolonged TV watching (OR=1.23, 1.08-1.41) and computer/mobile using and console playing time (OR=1.63, 1.36-1.95) were significant risk factors for LBP. Consumption of coffee, however, has yield conflicting results to be considered as a risk factor. Moreover, the researches on the correlation between sedentariness and high-intensity LBP are scarce and inconclusive. Sedentary behavior, whether in work or leisure time, associates with a moderate increase in the risk of LBP in adults, children and adolescents.
Learn More >Neuropathic pain, which is accompanied by an unpleasant sensation, affects the patient's quality of life severely. Considering the complexity of the neuropathic pain, there are huge unmet medical needs for it while current effective therapeutics remain far from satisfactory. Accordingly, exploration of mechanisms of neuropathic pain could provide new therapeutic insights. While numerous researches have pointed out the contribution of sensory neuron-immune cell interactions, other mechanisms of action, such as long non-coding RNAs (lncRNAs), also could contribute to the neuropathic pain observed in vivo. LncRNAs have more than 200 nucleotides and were originally considered as transcriptional byproducts. However, recent studies have suggested that lncRNAs played a significant role in gene regulation and disease pathogenesis. A substantial number of long non-coding RNAs were expressed differentially in neuropathic pain models. Besides, therapies targeting specific lncRNAs can significantly ameliorate the development of neuropathic pain, which reveals the contribution of lncRNAs in the generation and maintenance of neuropathic pain and provides a new therapeutic strategy. The primary purpose of this review is to introduce recent studies of lncRNAs on different neuropathic pain models.
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