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Emerging research has revealed that the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasomes contribute to the development of inflammatory and neuropathic pains. In addition, microglia are involved in the central nervous system (CNS) pain conduction. However, the relationship between NLRP3 inflammasome and dental inflammatory pain conduction is yet to be established. Therefore, this study aimed to investigate the roles of P2X7 and NLRP3/Caspase-1 (CASP1) in the inflammatory pain caused by pulpitis using a rat experimental pulpitis model. We discovered that the decreased pain threshold was inversely correlated with the increased expression of NLRP3, Caspase-1, P2X7, interleukin-1β (IL-1β), and IL-18 in the trigeminal ganglion and dorsal horn of the medulla after dental pulp exposure. Furthermore, the pain threshold of rats caused by pulpitis was increased by intraperitoneal injection of Brilliant Blue G (BBG), a P2X7 inhibitor, and the expression levels of NLRP3 and related inflammatory factors IL-1β and IL-18 were decreased. Moreover, treatment with 130nM KCl, a P2X7 inhibitor, significantly reduced the expression of NLRP3, IL-1β, IL-18, Caspase-1, and P2X7 in microglia after lipopolysaccharide(LPS) stimulation. In conclusion, our findings suggest that NLRP3/ CASP1 plays a vital role in the conduction of dental pain; the P2X7regulates NLRP3 pathway in the context of dental inflammatory pain conduction, and inhibiting P2X7 may be a potential strategy for dental inflammatory pain relief.
Learn More >Preventive treatment for refractory chronic cluster headache (rCCH) is challenging and many therapies have been tried.
Learn More >The Fibromyalgia Rapid Screening Tool (FiRST) was developed to screen people with chronic pain for Fibromyalgia (FM), especially in primary health care settings. This study aimed to translate the FiRST into Brazilian Portuguese and evaluate its measurement properties for an online application.
Learn More >Relying on anthropomorphism research, Illness Personification Theory (ILL-PERF) posits that individuals living with a chronic illness ascribe human-like characteristics to their illness. Herein we examine the personification of chronic pain using a new measure: the Ben-Gurion University Illness Personification Scale (BGU-IPS). Three samples of chronic pain patients (Sample 1 and 2 are distinct samples sharing similar characteristics, collected in the context of a cross-sectional design, Ns = 259, 263; Sample 3: a 2-waves longitudinal, N =163) completed the 12-item BGU-IPS, and measures of pain and related factors. An orthogonal, two-factor structure was revealed for the BGU-IPS pertaining to negative vs. positive personifications. Negative personification was associated with pain intensity and illness-related distress (e.g., depression and low adjustment to pain). Positive personification was correlated with hope, pain-related sense of control, and low depression. However, positive personification also augmented the associations between negative personification and several risk factors. : Pain personification, particularly as assessed via the BGU-IPS, plays a major role in (mal)adaptation to chronic pain.
Learn More >Non-specific low back pain (LBP) is a major global disease burden and childhood adversity predisposes to its development. The mechanisms are largely unknown. Here, we investigated if adversity in young rats augments mechanical hyperalgesia and how spinal cord microglia contribute to this. Adolescent rats underwent restraint stress, control animals were handled. In adulthood, all rats received two intramuscular injections of NGF/saline or both into the lumbar multifidus muscle. Stress induced in rats at adolescence lowered low back pressure pain threshold (PPT; p = 0.0001) and paw withdrawal threshold (PWT; p = 0.0007). The lowered muscle PPT persisted throughout adulthood (p = 0.012). A subsequent NGF in adulthood lowered only PPT (d = 0.87). Immunohistochemistry revealed changes in microglia morphology: stress followed by NGF induced a significant increase in ameboid state (p < 0.05). Repeated NGF injections without stress showed significantly increased cell size in surveilling and bushy states (p < 0.05). Thus, stress in adolescence induced persistent muscle hyperalgesia that can be enhanced by a mild-nociceptive input. The accompanying morphological changes in microglia differ between priming by adolescent stress and by nociceptive inputs. This novel rodent model shows that adolescent stress is a risk factor for the development of LBP in adulthood and that morphological changes in microglia are signs of spinal mechanisms involved.
Learn More >Chronic pain is one of the most frequent clinical problems after inguinal hernia surgery. Despite more than two decades of research and numerous publications, no evidence exists to allow for chronic postoperative inguinal pain (CPIP) specific treatment algorithms.
Learn More >Osteoarthritis (OA) is a complex chronic inflammatory disease characterized by articular degeneration and pain. Recent studies have identified interleukin 6 (IL-6) as a potential mediator leading to OA, but the therapeutic effects of inhibiting IL-6 signaling in intreating OA need to be further clarified. Here, we identified the intracellular signal transduction induced by recombinant IL-6 and focused on the impact of tyrphostin AG490 (a JAK2 inhibitor) on cartilage degeneration and OA pain. We found that IL-6 increased the inflammatory cytokines production and hypertrophic markers expression of primary mouse chondrocytes by activating JAK2/STAT3. Meanwhile, tyrphostin AG490 significantly attenuated articular degeneration and osteophyte formation in experimental mice with anterior cruciate ligament transection (ACLT) surgery. In vivo electrophysiological experiments showed that articular stimulation of IL-6 induced spinal hyperexcitability, which was prevented by coinjection of tyrphostin AG490. Specifically, compared with DMSO-treated ACLT mice, tyrphostin AG490 improved ambulate activity of mice and abolished the enhancement of serum bradykinin induced by IL-6. Together, we suggest that tyrphostin AG490 protected against progression of OA and improved OA prognosis by reducing cartilage degeneration and arthritis pain. Our findings provide further evidence for targeting IL-6 signaling in the treatment of OA.
Learn More >Acute burn pain is difficult to manage, and poorly managed pain can lead to deleterious consequences such as post-traumatic stress disorder, prolonged recovery, chronic pain and long-term dependence on opioids. Understanding the role of nursing in promoting self-efficacy and minimizing opioid use is valuable. It is unknown whether strategic efforts aimed at enhancing patient self-efficacy will improve pain managment and lessen opioid requirements in the adult burn population.
Learn More >People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI.
Learn More >Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway.
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