缓激肽对背根节神经元钠通道电流的作用

目的：观察缓激肽(bradykinin,BK)对大鼠背根节神经元电压依赖性钠通道电流的作用。方法：采用全细胞膜片钳技术,记录钠通道电流。结果：缓激肽剂量依赖性(0．01～10μmol／L)增高小细胞背根节神经元诱发放电频率;缓激肽剂量依赖性(O．01～10μmol／L)增加小细胞背根节神经元的河豚毒素不敏感(TTX—resistant,TTX—R)钠电流,对TTX敏感(TTX—sensitive,TTX-S)钠电流无明显影响。结论：缓激肽引起炎性痛的机制可能与TTX-R钠通道电流有关。     

Theory and rationale for surface EMG-assisted stretching as an adjunct to chronic musculoskeletal pain rehabilitation

A clinical protocol is reviewed, which utilizes supportive intervention, education, and surface EMG biofeedback to facilitate movement and to maximize effective stretching with chronic musculoskeletal pain patients. Support for this clinical protocol is provided with an overview of the physiological basis of stretching, surface EMG patterns associated with stretching, and the effects of pain and emotional factors on stretching and movement inhibition.     

The Use of Thermal Biofeedback in the Treatment of Pain Associated with Endometriosis: Preliminary Findings

Endometriosis is a common gynecological disease that causes marked physical and emotional distress in lives of women, resulting in dysmenorrhea, pain, or both throughout the menstrual cycle in over 96% of cases. A multiple case study design (N = 5) was employed to investigate the use of thermal biofeedback in the treatment of pain associated with endometriosis. The majority of participants (4 out of 5) were able to demonstrate mastery over hand temperature through thermal biofeedback. Of those participants, significant reductions in various aspects of pain were observed by the end of the study; one had a significant increase in Life Control; two had reductions in Pain Severity; three had a decrease in Affective Distress; and all 4 demonstrated reduction in Life Interference, as measured by the West Haven-Yale Multidimensional Pain Inventory. This is a preliminary study with a small sample size and without a control sample; hence, the results are considered only as suggestive of the potential use of biofeedback therapy in alleviating pain and associated symptomatology related to endometriosis. Further research is warranted.     

Tetraploid embryos rescue the early defects of tw5/tw5 mouse embryos

tclw5 is a t-complex recessive lethal mutation of the tw5-haplotype. Since tw5/tw5 embryos die soon after implantation, the tclw5 gene is thought to play an important role in early embryogenesis. Previous histological studies have demonstrated that tw5 homozygotes do not survive past the gastrulation stage due to extensive death of the embryonic ectoderm, whereas the extraembryonic tissues were less affected. In the present study, we demonstrate that tw5/tw5 embryos may be distinguished from wildtype littermates at embryonic (E) day 5.5. At this stage, the visceral endoderm of tw5/tw5 embryos appeared to be different, possessing smaller and fewer vacuoles compared to normal littermates. This led us to hypothesize that the visceral endoderm may be affected by tclw5. Confirmation was provided by the rescue of tw5/tw5 embryos following aggregation with tetraploid embryos. However, rescued embryos did not survive past E9.0 and displayed an underdeveloped posterior region. This would indicate that the actions of tclw5 extend beyond the midgestation stage.     

Estrous changes in vaginal nociception in a rat model of endometriosis

A rat model of endometriosis, in which pieces of uterine horn (versus fat in controls) are autotransplanted into the abdomen where they form cysts, reduces fecundity and produces vaginal hyperalgesia. The cysts gradually enlarge over a 2-month period postsurgically and then plateau. Cysts regress with low estrogen levels and reappear when they rise. Based on the hypothesis that the vaginal hyperalgesia depends upon the cysts, this study tested two predictions: that (1) the hyperalgesia would develop postsurgically in parallel with the cysts, and (2) the hyperalgesia would vary with estrous, being greatest when estrogen levels are high (proestrus) and least when low (estrus). In rats trained to escape vaginal distention, percentage escape responses to different distention volumes were measured across the rat's 4-day estrous cycle for 2.5 months before and up to 4 months after autotransplantation of uterus (n=9) or fat (n=6) in abdominal sites. Vaginal pressures were also measured. In rats with uterine but not fat autotransplants, escape percentages increased postsurgically over a 2-month period and then plateaued. The increase was greatest in proestrus and failed to occur in estrus. Vaginal pressures were unchanged in all groups. These results strongly support the hypothesis that the vaginal hyperalgesia depends upon the cysts. Because the cysts were located in sites remote from the vagina, the hyperalgesia involves viscero-visceral interactions and is likely centrally mediated, whereas the estrous modulation could involve hormonal actions either on the cysts or, more likely, on vaginal afferent fibers, and/or on central neurons.     

Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein

Morphine-6-glucuronide (M6G) is a substrate of P-glycoprotein (P-gp), which forms an outward transporter at the blood-brain barrier. Inhibition of P-gp may therefore be expected to cause increased CNS uptake of M6G. We directly assessed the spinal concentrations of M6G and its antinociceptive effects in rats following pharmacological inhibition of P-gp. Spinal cord tissue concentrations of M6G were assessed by microdialysis with probes transversally implanted through the dorsal horns of the spinal cord at level L4. Ten rats received M6G intravenously (0.018 mg/kg loading dose plus 0.00115 mg/kg/min for an 8-h infusion), five of them together with PSC833 to inhibit P-gp (32-h infusion, starting 24 h before the addition of M6G). Antinociceptive effects were explored by means of formalin tests. After having obtained evidence for enhanced CNS uptake and antinociception of M6G in the presence of PSC833, additional behavioural experiments were performed in another 32 rats to assess the dose dependency of the antinociceptive effects of M6G either with or without PSC833 in comparison with both PSC833 alone and placebo. Inhibition of P-gp increased the M6G concentrations in the spinal cord approximately three-fold whereas the plasma concentrations were increased only by a factor of 1.4, which resulted in a more than doubled spinal cord/plasma concentration ratio (from 0.08 +/- 0.03 for M6G alone to 0.17 +/- 0.08 for M6G plus PSC833). Antinociceptive effects of M6G were significantly enhanced by inhibition of P-gp. Inhibition of P-gp alters the transport of M6G across the blood-brain barrier, resulting in enhanced spinal cord uptake and enhanced antinociception.     

谷氨酸性突触在痛觉和记忆中的突触和分子机制

谷氨酸是哺乳动物脑中的兴奋性递质。中枢神经系统的谷氨酸性突触广泛参与痛觉传递,突触可塑性和递质的调节。谷氨酸的NMDA受体参与前脑相关的学习及功能。在这篇综述中,我们提出前脑的NMDA受体通过增强谷氨酸性突触传递导致长期性的炎痛。具有增强NMDA受体功能的小鼠会产生更多的慢性痛。NMDA NR2B受体抑制剂在未来可能被用来控制人类的慢性痛。     

Nerve growth factor induces P2X(3) expression in sensory neurons

Glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) are neuroprotective for subpopulations of sensory neurons and thus are candidates for pain treatment. However, delivering these factors to damaged neurons will invariably result in undamaged systems also being treated, with possible consequences for sensory processing. In sensory neurons the purinergic receptor P2X(3) is found predominantly in GDNF-sensitive nociceptors. ATP signalling via the P2X(3) receptor may contribute to pathological pain, suggesting an important role for this receptor in regulating nociceptive function. We therefore investigated the effects of intrathecal GDNF or NGF on P2X(3) expression in adult rat spinal cord and dorsal root ganglia (DRG). In control spinal cords, P2X(3) expression was restricted to a narrow band of primary afferent terminals within inner lamina II (II(i)). Glial cell line-derived neurotrophic factor treatment increased P2X(3) immunoreactivity within lamina II(i) but not elsewhere in the cord. Nerve growth factor treatment, however, induced novel P2X(3) expression, with intense immunoreactivity in axons projecting to lamina I and outer lamina II and to the ventro-medial afferent bundle beneath the central canal. In the normal DRG, we found a greater proportion of P2X(3)-positive neurons at cervical levels, many of which were large-diameter and calcitonin gene-related peptide-positive. In both cervical and lumbar DRG, the number of P2X(3)-positive cells increased following GDNF or NGF treatment. De novo expression of P2X(3) in NGF-sensitive nociceptors may contribute to chronic inflammatory pain.     

Highlights of human toxocariasis

Human toxocariasis is a helminthozoonosis due to the migration of Toxocara species larvae through human organism. Humans become infected by ingesting either embryonated eggs from soil (geophagia, pica), dirty hands or raw vegetables, or larvae from undercooked giblets. The diagnosis relies upon sensitive immunological methods (ELISA or western-blot) which use Toxocara excretory-secretory antigens. Seroprevalence is high in developed countries, especially in rural areas, and also in some tropical islands. The clinical spectrum of the disease comprises four syndromes, namely visceral larva migrans, ocular larva migrans, and the more recently recognized "common" (in adults) and "covert" (in children) pictures. Therapy of ocular toxocariasis is primarily based upon corticosteroids use, when visceral larva migrans and few cases of common or covert toxocariasis can be treated by anthelmintics whose the most efficient appeared to be diethylcarbamazine. When diagnosed, all of these syndromes require thorough prevention of recontamination (especially by deworming pets) and sanitary education.     

Correlation between in vitro and in vivo infectivity of Leishmania infantum clones

Eleven clones of a single strain of Leishmania infantum (MCAN/ES/88/ISS441, Doba) were analyzed for biological behavior in vivo and in vitro. Different clones showed differences in growth dependent upon the two culture media employed. All clones displayed only slight differences in H2O2 and NaNO2 sensitivity compared to the original strain, whereas in vitro infectivity for mouse peritoneal macrophages differed significantly among the clones. In vivo infections in hamsters correlated strongly with in vitro infectivity. The phenotypic differences found suggest a polyclonal structure for the Leishmania infantum strain studied.