Pannexin-1 (Panx1) is a large-pore membrane channel involved in the release of ATP and other signaling mediators. Little is known about the expression and functional role of Panx1 in the dorsal root ganglion (DRG) in the development of chronic neuropathic pain. In this study, we determined the epigenetic mechanism involved in increased Panx1 expression in the DRG after nerve injury. Spinal nerve ligation in rats significantly increased the mRNA and protein levels of Panx1 in the DRG but not in the spinal cord. Immunocytochemical labeling showed that Panx1 was primarily expressed in a subset of medium and large DRG neurons in control rats and that nerve injury markedly increased the number of Panx1-immunoreactive DRG neurons. Nerve injury significantly increased the enrichment of two activating histone marks (H3K4me2 and H3K9ac) and decreased the occupancy of two repressive histone marks (H3K9me2 and H3K27me3) around the promoter region of Panx1 in the DRG. However, nerve injury had no effect on the DNA methylation level around the Panx1 promoter in the DRG. Furthermore, intrathecal injection of the Panx1 blockers or Panx1-specific siRNA significantly reduced pain hypersensitivity induced by nerve injury. In addition, siRNA knockdown of Panx1 expression in a DRG cell line significantly reduced caspase-1 release induced by neuronal depolarization. Our findings suggest that nerve injury increases Panx1 expression levels in the DRG through altered histone modifications. Panx1 up-regulation contributes to the development of neuropathic pain and stimulation of inflammasome signaling. 相似文献
Visceral leishmaniasis (VL) or kala-azar mainly affects children in endemic areas. This study was conducted to determine the seroprevalence of VL using direct agglutination test (DAT) in children living in rural districts of Alborz Province located 30 km from Tehran capital city of Iran. Multi-stage cluster random sampling was applied. Blood samples were randomly collected from 1,007 children under 10 years of age in the clusters. A total of 37 (3.7%) of the studied population showed anti-Leishmania infantum antibodies with titers of ≥1:800. There was a significant association between positive sera and various parts of the rural areas of Alborz Province (P<0.002). Two children with anti-Leishmania infantum antibodies titers of ≥1:3,200 indicated kala-azar clinical features and treated with anti-leishmaniasis drugs in pediatric hospital. The findings of this study indicated that Leishmania infection is prevalent in rural areas of Alborz Province. Therefore, it is necessary to increase the awareness and alertness among physicians and public health managers, particularly in high-risk rural areas of the province in Iran. 相似文献
The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5 Hz to stimulate preferentially Aβ, Aδ, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5 Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD. 相似文献
The aim of this study is to investigate the role of the purinergic receptor P2X3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague–Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n = 8); (2) the model group (MG, n = 8); and (3) the model + electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han’s acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X3 receptor in the inter-colonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X3 receptor and ease the sensitivity to visceral pain. The P2X3 receptor plays an important role in IBS visceral pain. The different levels of P2X3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS. 相似文献
This study investigated the effects of age on upper erector spinae (UES), lower erector spinae (LES) and lower body (gluteus maximus; biceps femoris; and vastus lateralis) muscle activity during a repetitive lifting task. Twenty-four participants were assigned to two age groups: ‘younger’ (n = 12; mean age ± SD = 24.6 ± 3.6 yrs) and ‘older’ (n = 12; mean age = 46.5 ± 3.0 yrs). Participants lifted and lowered a box (13 kg) repetitively at a frequency of 10 lifts per minute for a maximum of 20 min. EMG signals were collected every minute and normalised to a maximum voluntary isometric contraction. A submaximal endurance test of UES and LES was used to assess fatigue. Older participants showed higher levels of UES and LES muscle activity (approximately 12–13%) throughout the task, but less fatigue compared to the younger group post-task completion. When lifting, lower-limb muscle activity was generally higher in older adults, although temporal changes were similar. While increased paraspinal muscle activity may increase the risk of back injury in older workers when repetitive lifting, younger workers may be more susceptible to fatigue-related effects. Education and training in manual materials handling should consider age-related differences when developing training programmes. 相似文献
Diabetic neuropathic pain (DNP) is a troublesome diabetes complication all over the world. P2X3 receptor (P2X3R), a purinergic receptor from dorsal root ganglion (DRG), has important roles in neuropathic pain pathology and nociceptive sensations. Here, we investigated the involvement of DRG P2X3R and the effect of 2 Hz electroacupuncture (EA) on DNP. We monitored the rats’ body weight, fasting blood glucose level, paw withdrawal thresholds, and paw withdrawal latency, and evaluated P2X3R expression in DRG. We found that P2X3R expression is upregulated on DNP, while 2 Hz EA is analgesic against DNP and suppresses P2X3R expression in DRG. To evaluate P2X3R involvement in pain modulation, we then treated the animals with A317491, a P2X3R specific antagonist, or α β-me ATP, a P2X3R agonist. We found that A317491 alleviates hyperalgesia, while α β-me ATP blocks EA’s analgesic effects. Our findings indicated that 2 Hz EA alleviates DNP, possibly by suppressing P2X3R upregulation in DRG.
Cryotherapy, or more commonly known as cold therapy, is the use of low temperatures in medical treatment. The most prominent use of cryotherapy is for cryosurgery where application of very low temperatures is used to ablate diseased tissue (e.g., most commonly in dermatology). Recent research, however, shows that low temperature may modulate collagen fibers beyond the already known effects of extreme cooling on joint pain relieve and inflammation. The goal of this brief review is to outline the known effects of extreme cooling on molecular, fiber and cell physiology and to leverage these properties in various potential medical applications. Specially, we will discuss potential cryotherapies for treatment of osteoarthritis and destruction of fat cells (i.e., cryolipolysis) for treatment of diabetes. Osteoarthritis (OA) is a degenerative disease, where joint pain and stiffness worsen over time. One of the most effective ways to relief joint pain is cooling the joint. Indeed, when evaluating different strategies to externally cool affected joints, it was found that reducing the internal joint temperature by ~ 10°C has beneficial effects in terms of pain reduction and regression in local inflammation. Moreover, collagen, whose deterioration is a major part of OA pathophysiology, regains elasticity after several freeze-thaw cycle. Finally, cartilage cells response to cold by increasing collagen formation and reducing matrix enzyme production, and adipose tissue within the joint that promote OA by supporting inflammation is susceptible to cold temperatures. Obesity is also a devastating disease that contributes to OA. Reduction of the temperature within the joint results in reduced inflammation, renewed collagen synthesis and reduced pain. Similarly, induction of extreme low temperatures in adipose tissue results in adipocytes loss without damage to surrounding tissues. Hence, cryotherapy has applications to modulation of collagen and fat cells for various therapies. 相似文献