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High-resolution structures of TRPV channels: unveiling a functionally diverse group of ion channels.
Transient receptor potential vanilloid (TRPV) channels are part of the superfamily of TRP ion channels and play important roles in widespread physiological processes including both neuronal and non-neuronal pathways. Various diseases such as skeletal abnormalities, chronic pain, and cancer are associated with dysfunction of a TRPV channel. In order to obtain full understanding of disease pathogenesis and create opportunities for therapeutic intervention, it is essential to unravel how these channels function at a molecular level. In the past decade, incredible progress has been made in biochemical sample preparation of large membrane proteins and structural biology techniques, including cryo-electron microscopy. This has resulted in high resolution structures of all TRPV channels, which has provided novel insights into the molecular mechanisms of channel gating and regulation that will be summarized in this review. This article is protected by copyright. All rights reserved.
Learn More >Despite evidence of the analgesic benefits of cannabis, there remains a relative scarcity of research on the short- and long-term effects of cannabis use in individuals with chronic pain.
Learn More >Chronic musculoskeletal pain disorders (CMPDs) are among the leading causes of disabilities across populations, resulting in high social and financial burden. This persistent pain condition may include the central sensitization (CS) phenomenon, which implies a wide range of symptoms and that may be taken into account in CMPD treatment. CS symptoms can be measured by the Central Sensitization Inventory (CSI). The aims of the study were to describe CS symptoms in patients suffering from several CMPDs and to analyze differences due to gender, age, and body mass index (BMI).
Learn More >To compare physical, sensory, and psychosocial factors between individuals with greater trochanteric pain syndrome and controls and to explore factors associated with pain and disability.
Learn More >Cytokines such as tumor necrosis factor (TNF) contribute to the transition from acute to persistent pain. Despite increasing incidence of obesity and its linkage with chronic pain and inflammation, cytokines predominantly produced by adipose tissue (adipokines) have received little attention. Here we aimed to explore the longitudinal trajectory of adipokines from the onset of acute low back pain (LBP) and identify combinations of adipokines and/or other features that predict outcome.
Learn More >Despite the association between chronic pain and post-traumatic stress disorder (PTSD), little is known about the longitudinal course of pain and PTSD during cancer treatment. We examined the prevalence of PTSD and chronic pain at three time periods in veterans with a diagnosis of cancer, and the relationship between the experience of pain and PTSD. Participants ( = 123) with oral-digestive cancers were recruited from the Veterans Healthcare System (age = 65.31 and SD = 9.13; 98.4% male) and completed face to face interviews at 6, 12, and 18 months post-diagnosis. Measures included the Post-traumatic Stress Disorder Checklist-Stressor-Specific version (PCL-S), Primary care PTSD (PC-PTSD), and the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Impact Scale. About one-third (26.8%) of the sample had chronic pain, defined as elevated pain at two time periods. About one-fifth (20.3%) endorsed symptoms of combat-related PTSD at 6 months, and 22.8% endorsed symptoms of cancer-related PTSD, exceeding a clinical cutoff for older adults (12 months = 21.1%, 18 months = 23.1%). Changes over time were observed for cancer-related PTSD symptom clusters of hyperarousal ( = 3.85 and = 0.023) and emotional numbing ( = 4.06 and = 0.018) with a statistically significant quadratic function increasing at 18 months. In logistic regression, individuals with both combat and cancer-related PTSD symptoms at six months had 8.49 times higher odds of experiencing chronic pain (χ = 25.91 and < 0.001; = 0.28). Persisting pain may be a concern in veterans with cancer. Individuals who have experienced traumatic events with persisting PTSD symptoms may be at elevated risk for chronic pain. Veterans with PTSD symptoms from both cancer and combat are at the highest risk to experience chronic pain.
Learn More >Central sensitization, including dysfunction of descending inhibitory pain pathways, may contribute to multisite pain in patients with chronic musculoskeletal conditions. Duloxetine is a centrally acting analgesic that effectively reduces pain in patients with knee osteoarthritis. Here we assessed the efficacy of duloxetine (60 mg/day) in Japanese patients (N = 353) with pain due to knee osteoarthritis based on the number of painful body sites, determined using the Michigan Body Map.
Learn More >Several investigations have indicated emotional processing impairment in migraineurs, while no report is available considering the automatic processing of emotional information. In this study, we aimed to characterize the pre-attentive processing of facial expressions in migraine sufferers by recording and analyzing expression-related visual mismatch negativity (EMMN).
Learn More >Neuropathic pain caused by a peripheral nerve injury constitutes a great challenge in clinical treatments due to the unsatisfactory efficacy of the current strategy. Microglial activation-mediated neuroinflammation is a major characteristic of neuropathic pain. Oleanolic acid is a natural triterpenoid in food and medical plants, and fulfills pleiotropic functions in inflammatory diseases. Nevertheless, its role in neuropathic pain remains poorly elucidated. In the current study, oleanolic acid dose-dependently suppressed LPS-evoked IBA-1 expression (a microglial marker) without cytotoxicity to microglia, suggesting the inhibitory efficacy of oleanolic acid in microglial activation. Moreover, oleanolic acid incubation offset LPS-induced increases in the iNOS transcript and NO releases from microglia, concomitant with the decreases in pro-inflammatory cytokine transcripts and production including IL-6, IL-1β, and TNF-α. Simultaneously, oleanolic acid shifted the microglial polarization from the M1 phenotype to the M2 phenotype upon LPS conditions by suppressing LPS-induced M1 marker CD16, CD86 transcripts, and enhancing the M2 marker Arg-1 mRNA and anti-inflammatory IL-10 levels. In addition, the LPS-induced activation of TLR4-NF-κB signaling was suppressed in the microglia after the oleanolic acid treatment. Restoring this signaling by the TLR4 plasmid transfection overturned the suppressive effects of oleanolic acid on microglial polarization-evoked inflammation. , oleanolic acid injection alleviated allodynia and hyperalgesia in SNL-induced neuropathic pain mice. Concomitantly, oleanolic acid facilitated microglial polarization to M2, accompanied by inhibition in inflammatory cytokine levels and activation of TLR4-NF-κB signaling. Collectively, these findings confirm that oleanolic acid may ameliorate neuropathic pain by promoting microglial polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype the TLR4-NF-κB pathway, thereby indicating its usefulness as therapeutic intervention in neuropathic pain.
Learn More >We evaluated the mechanisms underlying the spinal cord stimulation (SCS)-induced analgesic effect on neuropathic pain following spared nerve injury (SNI). On day 3 after SNI, SCS was performed for 6 h by using electrodes paraspinally placed on the L4-S1 spinal cord. The effects of SCS and intraperitoneal minocycline administration on plantar mechanical sensitivity, microglial activation, and neuronal excitability in the L4 dorsal horn were assessed on day 3 after SNI. The somatosensory cortical responses to electrical stimulation of the hind paw on day 3 following SNI were examined by using in vivo optical imaging with a voltage-sensitive dye. On day 3 after SNI, plantar mechanical hypersensitivity and enhanced microglial activation were suppressed by minocycline or SCS, and L4 dorsal horn nociceptive neuronal hyperexcitability was suppressed by SCS. In vivo optical imaging also revealed that electrical stimulation of the hind paw-activated areas in the somatosensory cortex was decreased by SCS. The present findings suggest that SCS could suppress plantar SNI-induced neuropathic pain via inhibition of microglial activation in the L4 dorsal horn, which is involved in spinal neuronal hyperexcitability. SCS is likely to be a potential alternative and complementary medicine therapy to alleviate neuropathic pain following nerve injury.
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