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Tobacco smoking-related diseases are estimated to kill more than 8 million people/year and most smokers are willing to stop smoking. The pharmacological approach to aid smoking cessation comprises nicotine replacement therapy (NRT) and inhibitors of the nicotinic acetylcholine receptor, which is activated by nicotine. Common side effects of oral NRT products include hiccoughs, gastrointestinal disturbances and, most notably, irritation, burning and pain in the mouth and throat, which are the most common reasons for premature discontinuation of NRT and termination of cessation efforts. Attempts to reduce the unwanted sensory side effects are warranted, and research discovering the most optimal masking procedures is urgently needed. This requires a firm mechanistic understanding of the neurobiology behind the activation of sensory nerves and their receptors by nicotine. The sensory nerves in the oral cavity and throat express the so-called transient receptor potential (TRP) channels, which are responsible for mediating the nicotine-evoked irritation, burning and pain sensations. Targeting the TRP channels is one way to modulate the unwanted sensory side effects. A variety of natural (Generally Recognized As Safe [GRAS]) compounds interact with the TRP channels, thus making them interesting candidates as safe additives to oral NRT products. The present narrative review will discuss (1) current evidence on how nicotine contributes to irritation, burning and pain in the oral cavity and throat, and (2) options to modulate these unwanted side-effects with the purpose of increasing adherence to NRT. Nicotine provokes irritation, burning and pain in the oral cavity and throat. Managing these side effects will ensure better compliance to oral NRT products and hence increase the success of smoking cessation. A specific class of sensory receptors (TRP channels) are involved in mediating nicotine's sensory side effects, making them to potential treatment targets. Many natural (Generally Recognized As Safe [GRAS]) compounds are potentially beneficial modulators of TRP channels.

This study explored changes in pain-related parameters, occupational function, occupational balance, lifestyle factors, and self-perceived health status in adults with chronic high-impact pain participating in an occupational therapy lifestyle intervention.

Pain catastrophizing in the aging population has not been studied in great detail. Existing investigations have reported conflicting results on the effects of age on pain catastrophizing in relation to pain responses. This study investigated the relationship between pain catastrophizing, and its individual components (rumination, magnification, and helplessness), and the responses to standardized experimental pain stimuli in old and young, healthy adults.

This review aims to analyse the published data on preclinical and human experimental and clinical adenosine modulation for pain management. We summarise the translatability of the adenosine pathway for further drug development and aim to reveal subgroups of pain patients that could benefit from targeting the pathway.

One of theories explaining the development of long-lasting symptoms after an acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection include changes in the methylation pattern of the host. The current study aimed to investigate whether DNA methylation levels associated with the angiotensin-converting enzyme 2 (ACE2) promoter are different when comparing individuals previously hospitalized due to COVID-19 who then developed long-lasting post-COVID pain with those previously hospitalized due to COVID-19 who did not develop post-COVID-19 pain symptoms. Non-stimulated saliva samples were obtained from a cohort of 279 (mean age: 56.5, SD: 13.0 years old, 51.5% male) COVID-19 survivors who needed hospitalization. Clinical data were collected from hospital medical records. Participants were asked to disclose pain symptoms developed during the first three months after hospital admission due to COVID-19 and persisting at the time of the interview. Methylations of five CpG dinucleotides in the ACE2 promoter were quantified (as percentages). Participants were evaluated up to 17.8 (SD: 5.3) months after hospitalization. Thus, 39.1% of patients exhibited post-COVID-19 pain. Most patients (77.05%) in the cohort developed localized post-COVID-19 pain. Headache and pain in the lower extremity were experienced by 29.4% of the patients. Seven patients received a post-infection diagnosis of fibromyalgia based on the presence of widespread pain characteristics (11.6%) and other associated symptoms. No significant differences in methylation percentages at any CpG location of the ACE2 promoter were identified when comparing individuals with and without post-COVID-19 pain. The current study did not observe differences in methylation levels of the ACE2 promoter depending on the presence or absence of long-lasting post-COVID-19 pain symptoms in individuals who needed hospitalization due to COVID-19 during the first wave of the pandemic. [ABSTRACT FROM AUTHOR]

Mirror Visual Feedback (MVF)-induced illusion of hand movements produces beneficial effects in patients with chronic pain. However, neurophysiological mechanisms underlying these effects are poorly known. In this preliminary study, we test the novel hypothesis that such an MVF-induced movement illusion may exert its effects by changing the activity in midline cortical areas associated with pain processing. Electrical stimuli with individually fixed intensity were applied to the left hand of healthy adults to produce painful and non-painful sensations during unilateral right-hand movements with such an MVF illusion and right and bilateral hand movements without MVF. During these events, electroencephalographic (EEG) activity was recorded from 64 scalp electrodes. Event-related desynchronization (ERD) of EEG alpha rhythms (8–12 Hz) indexed the neurophysiological oscillatory mechanisms inducing cortical activation. Compared to the painful sensations, the non-painful sensations were specifically characterized by (1) lower alpha ERD estimated in the cortical midline, angular gyrus, and lateral parietal regions during the experimental condition with MVF and (2) higher alpha ERD estimated in the lateral prefrontal and parietal regions during the control conditions without MVF. These preliminary results suggest that the MVF-induced movement illusion may affect nociception and neurophysiological oscillatory mechanisms, reducing the activation in cortical limbic and default mode regions. [ABSTRACT FROM AUTHOR]

It is known that SARS-CoV-2 can translocate via membrane ACE2 exopeptidase into the host cells, and thus hypomethylation of ACE2 possibly upregulates its expression, enhancing the risk of SARS-CoV-2 infection. This study investigated if DNA methylation levels of the ACE2 promoter are associated with the development of post-COVID-19 symptomatology in a cohort of COVID-19 survivors who had been previously hospitalized. Non-stimulated saliva samples were obtained from 279 (51.5 male, mean age: 56.5 ± 13.0 years old) COVID-19 survivors who were hospitalized during the first wave of the pandemic. A face-to-face interview in which patients described the presence of post-COVID-19 symptoms (defined as a symptom that started no later than three months after SARS-CoV-2 infection) that they suffered from to an experienced healthcare trainer was conducted. Methylation of five CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. The percentage of methylation (%) was associated with the presence of the following reported post-COVID-19 symptoms: fatigue, dyspnea at rest, dyspnea at exertion, brain fog, memory loss, concentration loss, or gastrointestinal problems. Participants were assessed a mean of 17.8 (SD: 5.3) months after hospitalization. At that time, 88.1% of the patients experienced at least one post-COVID-19 symptom (mean number for each patient: 3.0; SD: 1.9 post-COVID-19 symptoms). Dyspnea at exertion (67.3%), fatigue (62.3%), and memory loss (31.2%) were the most frequent post-COVID-19 symptoms in the sample. Overall, the analysis did not reveal any difference in the methylation of the ACE2 promoter in any of the CpG locations according to the presence or absence of fatigue, dyspnea at rest, dyspnea at exertion, memory loss, brain fog, concentration loss, and gastrointestinal problems. This study did not find an association between methylation of ACE2 promoter and the presence of post-COVID-19 fatigue, dyspnea, cognitive or gastrointestinal problems in previously hospitalized COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Background: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. Methods: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. Discussion: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of administrating Remdesivir at the acute COVID-19 phase on developing post-COVID symptoms in previously hospitalized COVID-19 survivors by controlling factors such as age, sex, body mass index, and vaccination status. A case-control study was performed. Hospitalized COVID-19 survivors who had received intravenous Remdesivir during the acute phase (n = 216) were matched by age, sex, body mass index, and vaccination status with survivors who did not receive antiviral treatment (n = 216). Participants were asked to self-report the presence of any post-COVID symptom (defined as a symptom that started no later than three months after infection) and whether the symptom persisted at the time of study (mean: 18.4, SD: 0.8 months). Anxiety levels (HADS-A), depressive symptoms (HADS-D), sleep quality (PSQI), and severity/disability (FIC) were also compared. The multivariate analysis revealed that administration of Remdesivir at the acute COVID-19 phase was a protective factor for long-term COVID development (OR0.401, 95%CI 0.256–0.628) and specifically for the following post-COVID symptoms: fatigue (OR0.399, 95%CI 0.270–0.590), pain (OR0.368, 95% CI 0.248–0.548), dyspnea at rest (OR0.580, 95%CI 0.361–0.933), concentration loss (OR0.368, 95%CI 0.151–0.901), memory loss (OR0.399, 95%CI 0.270–0.590), hair loss (OR0.103, 95%CI 0.052–0.207), and skin rashes (OR0.037, 95%CI 0.005–0.278). This study supports the potential protective role of intravenous administration of Remdesivir during the COVID-19 acute phase for long-lasting post-COVID symptoms in previously hospitalized COVID-19 survivors. [ABSTRACT FROM AUTHOR]

ObjectivePain sensitization is associated with pain severity in knee osteoarthritis (OA), but its cause in humans is not well understood. We examined whether inflammation, assessed as synovitis and effusion on magnetic resonance imaging (MRI), or mechanical load, assessed as bone marrow lesions (BMLs), was associated with sensitization in knee OA.MethodsSubjects in the Multicenter Osteoarthritis Study, a National Institutes of Health-funded cohort of persons with or at risk of knee OA, underwent radiography and MRI of the knee, and standardized quantitative sensory testing (temporal summation and pressure pain threshold [PPT]) of the wrist and patellae at baseline and 2 years later. We examined the relation of synovitis, effusion, and BMLs to temporal summation and PPT cross-sectionally and longitudinally.ResultsThere were 1,111 subjects in the study sample (mean age 67 years, mean body mass index 30 kg/m(2) , 62% female). Synovitis was associated with a significant decrease in PPT at the patella (i.e., more sensitized) over 2 years (adjusted β -0.30 [95% confidence interval (95% CI) -0.52, -0.08]). Effusion was similarly associated with a decrease in PPT at the wrist (adjusted β -0.24 [95% CI -0.41, -0.08]) and with risk of incident temporal summation at the patella (adjusted OR 1.54 [95% CI 1.01, 2.36]). BMLs were not associated with either quantitative sensory testing measure.ConclusionInflammation, as evidenced by synovitis or effusion, is associated with pain sensitization in knee OA. In contrast, BMLs do not appear to contribute to sensitization in knee OA. Early targeting of inflammation is a reasonable strategy to test for prevention of sensitization and through this, reduction of pain severity, in knee OA.

ObjectivesIt is not clear whether heightened pain sensitivity in knee osteoarthritis (OA) is related to sensitisation induced by nociceptive input from OA pathology ('state') versus other confounding factors. Conversely, some individuals may be predisposed to sensitisation irrespective of OA ('trait').MethodsThe Multicenter Osteoarthritis Study is a longitudinal cohort of persons with or at risk of knee OA. We obtained knee X-rays, pain questionnaires and comprehensive assessment of factors that can influence pain sensitivity. We examined the relation of sensitisation and sensitivity assessed by mechanical temporal summation (TS) and pressure pain thresholds (PPTs) to knee OA and knee pain severity. To test whether sensitisation and sensitivity is a 'state' induced by OA pathology, we examined the relation of PPT and TS to knee OA duration and severity.ResultsIn 2126 subjects (mean age 68, mean body mass index (BMI) 31, 61% female), PPT and TS were not associated with radiographic OA (ORs 0.9-1.0 for PPT and TS; p>0.05). However, PPT and TS were associated with pain severity (ORs: 1.7-2.0 for PPT; 1.3-1.6 for TS; p

The COVID-19 pandemic has affected millions of individuals worldwide. Pain has emerged as a significant post-COVID-19 symptom. This study investigated the incidence, characteristics, and risk factors of post-COVID chronic pain (PCCP) in Thailand. A cross-sectional study was conducted in participants who had been infected, including those hospitalized and monitored at home by SARS-CoV-2 from August to September 2021. Data were collected for screening from medical records, and phone interviews were done between 3 to 6 months post-infection. Participants were classified into 1) no-pain, 2) PCCP, 3) chronic pain that has been aggravated by COVID-19, or 4) chronic pain that has not been aggravated by COVID-19. Pain interference and quality of life were evaluated with the Brief Pain Inventory and EuroQol Five Dimensions Five Levels Questionnaire. From 1,019 participants, 90% of the participants had mild infection, assessed by WHO progression scale. The overall incidence of PCCP was 3.2% (95% CI 2.3–4.5), with 2.8% (95% CI 2.0–4.1) in mild infection, 5.2% (95% CI 1.2–14.1) in moderate infection and 8.5% (95% CI 3.4–19.9) in severe infection. Most participants (83.3%) reported pain in the back and lower extremities and were classified as musculoskeletal pain and headache (8.3%). Risk factors associated with PCCP, included female sex (relative risk [RR] 2.2, 95% CI 1.0–4.9) and greater COVID-19 severity (RR 3.5, 95% CI 1.1–11.7). Participants with COVID-19-related exacerbated chronic pain displayed higher pain interferences and lower utility scores than other groups. In conclusion, this study highlights the incidence, features, and risk factors of post-COVID chronic pain (PCCP) in Thailand. It emphasizes the need to monitor and address PCCP, especially in severe cases, among females, and individuals with a history of chronic pain to improve their quality of life in the context of the ongoing COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

This review aims to analyse the published data on preclinical and human experimental and clinical adenosine modulation for pain management. We summarise the translatability of the adenosine pathway for further drug development and aim to reveal subgroups of pain patients that could benefit from targeting the pathway. Chronic pain patients suffer from inadequate treatment options and drug development is generally impaired by the low translatability of preclinical pain models. Therefore, validating the predictability of drug targets is of high importance. Modulation of the endogenous neurotransmitter adenosine gained significant traction in the early 2000s but the drug development efforts were later abandoned. With the emergence of new drug modalities, there is a renewed interest in adenosine modulation in pain management. In both preclinical, human experimental and clinical research, enhancing adenosine signalling through the adenosine receptors, has shown therapeutic promise. A special focus has been on the A1 and A3 receptors both of which have shown great promise and predictive validity in neuropathic pain conditions. Adenosine modulation shows predictive validity across preclinical, human experimental and clinical investigations. The most compelling evidence is in the field of neuropathic pain, where adenosine has been found to alleviate hyperexcitability and has the potential to be disease-modifying. Adenosine modulation show therapeutic potential in neuropathic pain if selective and safe drugs can be developed. New drug modalities such as RNA therapeutics and cell therapies may provide new options. [ABSTRACT FROM AUTHOR]