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Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat.
Learn More >To use daily data collected via a smartphone app for characterisation of patient-reported and "symptom-based" (using an a priori definition) flares in an adult idiopathic inflammatory myopathy (IIM) cohort.
Learn More >The concept of "invalidation" refers to the patient's perception that the social environment does not recognize their medical condition. This study explores and describes invalidation experiences among Swedish patients with chronic widespread pain with regard to sociodemographic and pain characteristics, impact of pain, self-reported health, and symptoms of anxiety and depressive. Methods: A cross-sectional design using questionnaires, including sociodemographic and pain variables, the Illness Invalidation Inventory (Likert scale items regarding 5 sources), the Hospital Anxiety and Depression Scale, and the Short-Form General Health Survey. Descriptive and univariate analyses were applied. Results: Of the 152 respondents, 91% were women. Swedish patients with chronic widespread pain experienced invalidation to a large extent from all sources. The highest scores for invalidation were reported from contacts with social services (68%), and the lowest from spouses (30%). Being younger (p < 0.006), having periodic pain (p = 0.011), and having had more frequent visits to a doctor in the previous year (p = 0.007) were characteristics associated with higher invalidation scores. Experiences of invalidation were associated with worse self-reported mental health scores (r = -0.29 to -0.46). Conclusion: Since patients with chronic widespread pain frequently experience invalidation from the social environment, this further challenge in daily life must be taken into consideration in pain management within multimodal pain rehabilitation.
Learn More >To explore the associations between habitual self-reported physical activity, pain sensitivity and patient-reported outcomes (including pain intensity) in patients with chronic pain. Design: Cross-sectional, experimental study. Subjects: Patients (n = 78), age range 18-65 years, with different chronic pain conditions (> 3 months) were compared with age- and gender-matched healthy controls (n = 98). Methods: Multivariate correlations between self-reported physical activity, pressure pain thresholds, and patient-reported outcome measures were assessed. Results: Lower perceived health status (p < 0.001, Cohen's d = 2.34), higher levels of depression (p < 0.001, Cohen's d = 1.77), and lower pressure pain tolerance threshold (p < 0.001, Cohen's d = 1.66) were the most prominent variables discriminating patients from controls. In patients, bivariate and multivariate analyses showed that higher pressure pain tolerance was associated with male gender, lower pain intensity and fewer painful regions, higher self-efficacy and more self-reported physical activity, but not with lower levels of anxiety and depression. Conclusion: Pressure pain tolerance thresholds, as well as degree of depression and perceived health status discriminated between patients and controls, and there was an association between pain tolerance and level of self-reported physical activity in patients. This study highlights the importance of further research into how increased physical activity may improve pain sensitivity in patients with chronic pain.
Learn More >Fibromyalgia syndrome (sFM) is one of the most common causes of chronic pain. This study aimed to assess the presence of small and large fiber impairment in fibromyalgic patients by applying validated scores used in the screening for diabetic neuropathy. The endpoints for the study were the assessment of neuropathy prevalence in sFM patients using the NerveCheck Master (NCM), the Michigan Neuropathy Screening Instrument (MNSI), the Diabetic Neuropathy Symptom (DNS) and the Douleur Neuropathique 4 Questions (DN4). The sample was composed of 46 subjects: subjects with sFM ( = 23) and healthy controls (HC) ( = 23). The positivity rates in each group for DN4 were significantly different ( < 0.001), with a prevalence in symptomatic subjects of 56.3% ( = 9) among sFM individuals. A similar difference was also observed with the DNS total score ( < 0.001). NCM and MNSI did not disclose significant differences between the two groups. This finding seems to confirm the data regarding the prevalence of a neuropathic pain in sFM patients.
Learn More >Recently, a growing body of evidence has emerged regarding the interplay between microbiota and the nervous system. This relationship has been associated with several pathological conditions and also with the onset and regulation of pain. Dysregulation of the axis leads to a huge variety of diseases such as visceral hypersensitivity, stress-induced hyperalgesia, allodynia, inflammatory pain and functional disorders. In pain management, probiotics have shown promising results. This narrative review describes the peripheral and central mechanisms underlying pain processing and regulation, highlighting the role of the gut-brain axis in the modulation of pain. We summarized the main findings in regard to the stress impact on microbiota's composition and its influence on pain perception. We also focused on the relationship between gut microbiota and both visceral and inflammatory pain and we provided a summary of the main evidence regarding the mechanistic effects and probiotics use.
Learn More >Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are promising targets for neuropathic pain and other CNS disorders. Based on our previous lead compound SIH 3, we designed and synthesized a series of 4-methylsulfonylphenyl semicarbazones and evaluated for FAAH and MAGL inhibition properties. Most of the compounds showed potency towards both enzymes with leading FAAH selectivity. Compound (Z)-2-(2,6-dichlorobenzylidene)-N-(4-(methylsulfonyl)phenyl)hydrazine-1-carboxamide emerged as the lead inhibitor against both FAAH (IC = 11 nM) and MAGL (IC = 36 nM). The lead inhibitor inhibited FAAH by non-competitive mode, but showed a mixed-type inhibition against MAGL. Molecular docking study unveiled that the docked ligands bind favorably to the active sites of FAAH and MAGL. The lead inhibitor interacted with FAAH and MAGL via π-π stacking via phenyl ring and hydrogen bonding through sulfonyl oxygen atoms or amide NH. Moreover, the stability of docked complexes was rationalized by molecular simulation studies. PAMPA assay revealed that the lead compound is suitable for blood-brain penetration. The lead compound showed better cell viability in lipopolysaccharide-induced neurotoxicity assay in SH-SY5Y cell lines. Further, in-vivo experiments unveiled that dual inhibitor was safe up to 2000 mg/kg with no hepatotoxicity. The dual FAAH-MAGL inhibitor produced significant anti-nociceptive effect in the CCI model of neuropathic pain without altering locomotion activity. Lastly, the lead compound exhibited promising ex-vivo FAAH/MAGL inhibition activity at the dose of 10 mg/kg and 20 mg/kg. Thus, these findings suggest that the semicarbazone-based lead compound can be a potential template for the development of agents for neuropathic pain.
Learn More >Casitas B-lineage lymphoma b (Cbl-b) is one of the E3 ubiquitin ligases that ubiquitinate Tropomyosin-related kinase A (TrkA), a key nerve growth factor receptor involved in the pathological pain. Here we found that Cbl-b was abundant in dorsal root ganglion (DRG) neurons of mice and co-localized with TrkA. Ubiquitination of TrkA by Cbl-b exerted a tonic negative control over the protein level of TrkA. Knockdown of Cbl-b caused TrkA accumulation in DRGs and evoked mechanical and heat hypersensitivity in intact mice. Our data showed that knee osteoarthritis induced by destabilization of the medial meniscus (DMM) led to the dissociation of Cbl-b with TrkA in DRG neurons, which impaired the ability of Cbl-b to ubiquitinate TrkA and served as an important mechanism to cause TrkA-dependent pain sensitization. Viral expression of constitutively active Cbl-b in DRGs of osteoarthritic mice effectively repressed TrkA protein level and more importantly, alleviated mechanical allodynia and heat hyperalgesia. Viral delivery of Cbl-b through intra-articular route generated a similar analgesic action. These data suggested that ubiquitination of TrkA by Cbl-b might represent an effective way to treat the osteoarthritic pain.
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