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Worldwide, cancer pain management follows the WHO three step analgesic ladder. Using weak opioids (e.g. codeine) at step two is debatable with low dose strong opioids potentially better, particularly in low and middle-income countries where weak opioids are expensive. We wanted to assess the efficiency, safety and cost of omitting step two of the WHO ladder.
Learn More >Migraine is a complex neurovascular disorder characterized by recurrent attacks of pain and other associated symptoms. Emotional-affective aspects are important components of pain, but so far they have been little explored in animal models of migraine. In this study, we aimed to explore the correlation between trigeminal hyperalgesia and affective status or behavioral components in a migraine-specific animal model. Male Sprague-Dawley rats were treated with nitroglycerin (10 mg/kg, i.p.) or its vehicle. Four hours later, anxiety, motor/exploratory behavior and grooming (a nociception index) were evaluated with the open field test. Rats were then exposed to formalin in the orofacial region to evaluate trigeminal hyperalgesia. The data analysis shows an inverse correlation between trigeminal hyperalgesia and motor or exploratory behavior, and a positive association with anxiety-like behavior or self-grooming. These findings further expand on the translational value of the migraine-specific model based on nitroglycerin administration and prompt additional parameters that can be investigated to explore migraine disease in its complexity.
Learn More >This study explored the bidirectional relationship between fibromyalgia and migraine among probands with either of the two disorders and their unaffected siblings.
Learn More >Modern genetic approaches in animal models have unveiled novel itch-specific neural pathways, emboldening a paradigm in which drugs can be developed to selectively and potentially target itch in a variety of chronic pruritic conditions. In recent years, kappa-opioid receptors (KOR) and mu-opioid receptors (MOR) have been implicated in both the suppression and promotion of itch, respectively, by acting in both the peripheral and central nervous systems. The precise mechanisms by which agents that modulate these pathways to alleviate itch remains an active area of investigation. Notwithstanding this, a number of agents have demonstrated efficacy in clinical trials that influence both KOR and MOR signaling. Herein, we summarize a number of opioid receptor modulators in development and their promising efficacy across a number of chronic pruritic conditions, such as atopic dermatitis, uremic pruritus, and beyond.
Learn More >Co-occurring pain conditions that affect overlapping body regions are complicated by the distinction between primary versus secondary pain conditions. We investigate the occurrence of headache and painful temporomandibular disorder (TMD) in a community-based, cross-sectional study of U.S. adults in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA-II) study. A specific goal was to determine if headache attributed to TMD is separable from primary headache.Using DC/TMD and ICHD-3 criteria, three groups of individuals were created: a) headache without TMD; b) headache comorbid with TMD; and c) headache attributed to TMD. Regression models compared study groups according to demographic and comorbid characteristics, and post-hoc contrasts tested for differences. Descriptive statistics and Cohen's d effect size were computed, by group, for each predictor variable. Differences in continuous predictors were analyzed using one-way ANOVA.Nearly all demographic and comorbid variables distinguished the combined headache and TMD groups from the group with headache alone. Relative to the reference group with primary headache alone, markers related to headache, TMD, somatic pain processing, psychosocial, and health conditions were substantially greater in both headache comorbid with TMD and headache attributed to TMD, attesting to their qualitative similarities. However, effect sizes relative to the reference group were large for headache comorbid with TMD and larger again for headache attributed to TMD, attesting to their separability in quantitative terms.In summary, the presence of overlapping painful TMD and headache adds substantially to the biopsychosocial burden of headache and points to the importance of comprehensive assessment and differential management.
Learn More >Alterations of empathy for others' pain among patients with chronic pain remained inconsistent. Here, applying a capsaicin-based ongoing pain model on healthy participants, this study investigated how ongoing first-hand pain influences empathic reactions to vicarious pain stimuli. Healthy participants were randomly treated with topical capsaicin cream (capsaicin group) or hand cream (control group) on the left forearm. Video clips showing limbs in painful and non-painful situations were used to induce empathic responses. The capsaicin group showed greater empathic neural responses in the right primary somatosensory cortex (S1) than the control group but smaller responses in the left anterior insula (AI) accompanied with smaller empathic pain-intensity ratings. Notably, the intensity of ongoing pain negatively correlated with empathy-related neural responses in the left AI. Inter-subject phase synchronization analysis was used to assess stimulus-dependent dynamic functional connectivity within or between brain regions engaged in pain empathy. The capsaicin group showed greater empathy-related neural synchronization within S1 and between S1 and AI, but less synchronization within AI and between AI and MCC. Behaviorally, the differential inter-subject pain-intensity rating alignment between painful and non-painful videos was more positive for the capsaicin group than for the control group, and this effect was partially mediated by the inter-subject neural synchronization between S1 and AI. These results suggest that ongoing first-hand pain facilitates neural activation and synchronization within brain regions associated with empathy-related somatosensory resonance at the cost of inhibiting activation and synchronization within brain regions engaged in empathy-related affective sharing.
Learn More >Growing evidence indicates that transient receptor potential (TRP) channels contribute to different forms of pruritus. However, the endogenous mediators that cause itch via TRP channels signaling are poorly understood. Herein, we show that genetic deletion or pharmacological antagonism of TRP vanilloid 4 (TRPV4) attenuated itch in a mouse model of psoriasis induced by topical application of imiquimod. Human psoriatic lesions showed increased expression of several miRNAs, including the miR-203b-3p, which induced a Ca response in rodent dorsal root ganglion neurons and scratching behavior in mice via serotonin receptor 2B (5-HTR2B) activation and the protein kinase C-dependent phosphorylation of TRPV4. Computer simulation revealed that the miR-203b-3p core sequence (GUUAAGAA) that causes 5-HTR2B/TRPV4-dependent itch, targets the extracellular side of 5-HTR2B by interacting with a portion of the receptor pocket consistent with its activation. Overall, we reveal the unconventional pathophysiological role of an extracellular miRNA that can behave as an itch promoter via 5-HTR2B and TRPV4.
Learn More >Chemotherapy-induced peripheral neuropathy is a debilitating pain syndrome produced as a side effect of antineoplastic drugs like paclitaxel. Despite efforts, the currently available therapeutics suffer from serious drawbacks like unwanted side effects, poor efficacy and provide only symptomatic relief. Hence, there is a need to find new therapeutic alternatives for the treatment of Chemotherapy-induced peripheral neuropathy.
Learn More >The McGill Quality of Life Questionnaire-Revised (MQoL-R) is the gold standard for assessing QoL in end-of-life, chronic patients; however, an Italian standardization is lacking.
Learn More >Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng. Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. We found that various doses of Rh2 intrathecal injection dose-dependently attenuated SNI-induced mechanical allodynia and thermal hyperalgesia. Rh2 also inhibited microglia and astrocyte activation in the spinal cord of a murine SNI model. Rh2 treatment inhibited SNI-induced increase of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. Expression of miRNA-21, an endogenous ligand of Toll like receptor (TLR)8 was also decreased. Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.
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