Accepted

The offset of a painful and unpleasant sensation can elicit pleasure. This phenomenon, namely pleasant pain relief (PPR), is attracting growing interest in research. While the cold pressor test (CPT) has been frequently used to study the inhibition of pain by the administration of another painful stimulation (inhibitory conditioned pain modulation; ICPM), a preliminary study from our research team has shown that CPT can also elicit a robust and long-lasting PPR. However, its effects on pain relief and inhibition vary greatly between subjects. Although substantial research has been carried out on inter-individual variability in the case of ICPM, the same cannot be said of PPR. Therefore, the current study sought to identify clusters of healthy volunteers with similar dynamic pain responses during the CPT, using a data-driven approach, and to investigate the inter-subject variability for PPR and ICPM.

Polymyalgia rheumatica (PMR) is an inflammatory disease affecting older adults characterized by aching pain and morning stiffness of the shoulder and pelvic girdles. Moreover, PMR can be associated with giant cell arteritis (GCA). Generally, PMR is highly responsive to steroids, reaching complete remission in the majority of cases. However, the possibility of occult diseases, including extra-cranial GCA, should be excluded. 18F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) is able to detect the presence of peri-/articular or vascular inflammation, which may be both present in PMR, thus representing a useful diagnostic tool, mainly in presence of extra-cranial GCA. We retrospectively evaluated all consecutive patients who received the diagnosis of PMR in our rheumatology clinic, classified according to the 2012 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria, in the period between April 2020 and May 2022. Among this case series, we selected the patients who underwent F-FDG-positron emission tomography (PET) because of the persistent increase of acute phase reactants (APR) besides the steroid therapy. Eighty patients were diagnosed with PMR. Nine out of them also presented arthritis of the wrists during the follow-up, whereas none showed signs of cranial GCA at the diagnosis. Seventeen out of eighty subjects (mean age 71.5 ± 7.5 years; M/F 2/15) presented persistent increase of erythrocyte sedimentation rate (mean ESR 44.2 ± 20.8 mm/h) and/or C-reactive protein (mean CRP 25.1 ± 17 mg/l), thus they underwent total body F-FDG-PET/CT. Large vessel F-FDG uptake indicating an occult GCA was found in 5/17 (29.4%) cases. Twelve out of seventeen (70.6%) patients showed persistence of peri-/articular inflammation, suggesting a scarce control of PMR or the presence of chronic arthritis. Finally, in 2 cases, other inflammatory disorders were found, namely an acute thyroiditis and a hip prosthesis occult infection. F-FDG-PET/CT in PMR patients with persistent increase of APR is a useful diagnostic technique in order to detect occult GCA, persistence of active PMR or other misdiagnosed inflammatory diseases.

The research and clinical applications of exercise therapy to the treatment of Parkinson's disease (PD) are increasing. Pain is among the important symptoms affecting the daily motor function and quality of life of PD patients. This paper reviewed the progress of research on different exercise therapies for the management of pain caused by PD and described the role and mechanism of exercise therapy for pain relief. Aerobic exercise, strength exercise, and mind-body exercise play an effective role in pain management in PD patients. The pain suffered by PD patients is divided into central neuropathic, peripheral neuropathic, and nociceptive pain. Different types of pain may coexist with different mechanistic backgrounds and treatments. The analgesic mechanisms of exercise intervention in PD-induced pain include altered cortical excitability and synaptic plasticity, the attenuation of neuronal apoptosis, and dopaminergic and non-dopaminergic analgesic pathways, as well as the inhibition of oxidative stress. Current studies related to exercise interventions for PD-induced pain suffer from small sample sizes and inadequate research of analgesic mechanisms. The neurophysiological effects of exercise, such as neuroplasticity, attenuation of neuronal apoptosis, and dopaminergic analgesic pathway provide a sound biological mechanism for using exercise in pain management. However, large, well-designed randomized controlled trials with improved methods and reporting are needed to evaluate the long-term efficacy and cost-effectiveness of exercise therapy for PD pain.

Non-specific low back pain affects people of all ages and is a leading contributor to disease burden worldwide. Chronic low back pain (LBP) reduces working hours, increases comorbidities, and increases rehabilitation needs. The aim of this study was to evaluate whether there were differences in pain, dysfunction, and psychological factors between two groups. The supplementary demonstrated the relationship between these influencing factors and anxiety. A cross-sectional study was designed to analyze the differences in pain, disability, and psychological function in non-specific LBP patients with and without anxiety. In total, 60 subjects were divided into two groups based on self-rated anxiety scores: 30 patients with SAS score ≥50 were in the low back pain with anxiety group, and 30 for the LBP without anxiety group with SAS score <50. The pain intensity was assessed using the Visual Analog Scale; psychological function, using the Pain Anxiety Symptoms Scale, the Tampa Scale for Kinesiophobia, and the Fear Avoidance Beliefs Questionnaire; functional disability, using the Oswestry Disability Index and the Roland-Morris Disability Questionnaire; quality of life using 36-Item Short-Form Health Survey questionnaire; and the quality of sleep using Pittsburgh Sleep Quality Index, and the relationships between variables and anxiety scores were estimated using Spearman correlation analysis. A total of 60 participants were enrolled after self-rated anxiety was assessed and the full investigation was finished. The analyses showed significant differences of pain intensity ( = 0.034, disability (ODI, = 0.007; RMDQ, = 0.012) and psychological function (TSK, = 0.000; PASS, = 0.009; FABQ, = 0.000; SF-36, = 0.000; and PSQI, = 0.000) between the two groups. Spearman correlation analysis showed that the anxiety score had significant positive correlations with functional disability (ODI, = 0.004 and 95% CI = 0.112-0.573; RMDQ, = 0.003, 95% CI = 0.135-0.586) and psychological function (TSK, = 0.001, 95% CI = 0.174-0.612), excellent positive correlation with quality of sleep (PASS, = 0.025, 95% CI = 0.031-0.512), and strongly negative correlations with the quality of life (SF-36, = 0.000, 95% CI = 0.761-0.433). We recognized that anxiety in low back pain patients was mainly due to interaction with the intensity of pain, disability level, and a mass of psychological function. The future research direction could be to alleviate the anxiety on the comprehensive efficacy of patients with low back pain.

Minimizing acute postsurgical pain (APSP) remains a challenge, despite extensive research about it. This study comprehensively analyzed the literature on APSP to assess how the field has developed and where it may go in the future.

Millions of people suffer from arthritis worldwide, consistently struggling with daily activities due to debilitating pain evoked by this disease. Perhaps the most intensively investigated type of inflammatory arthritis is rheumatoid arthritis (RA), where, despite considerable advances in research and clinical management, gaps regarding the neuroimmune interactions that guide inflammation and chronic pain in this disease remain to be clarified. The pain and inflammation associated with arthritis are not isolated to the joints, and inflammatory mechanisms induced by different immune and glial cells in other tissues may affect the development of chronic pain that results from the disease. This review aims to provide an overview of the state-of-the-art research on the roles that innate immune, and glial cells play in the onset and maintenance of arthritis-associated pain, reviewing nociceptive pathways from the joint through the dorsal root ganglion, spinal circuits, and different structures in the brain. We will focus on the cellular mechanisms related to neuroinflammation and pain, and treatments targeting these mechanisms from the periphery and the CNS. A comprehensive understanding of the role these cells play in peripheral inflammation and initiation of pain and the central pathways in the spinal cord and brain will facilitate identifying new targets and pathways to aide in developing therapeutic strategies to treat joint pain associated with RA.

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.