Inward currents induced by ischemia in rat spinal cord dorsal horn neurons

Hypoxia and ischemia occur in the spinal cord when blood vessels of the spinal cord are compressed under pathological conditions such as spinal stenosis, tumors, and traumatic spinal injury. Here by using spinal cord slice preparations and patch-clamp recordings we investigated the influence of an ischemia-simulating medium on dorsal horn neurons in deep lamina, a region that plays a significant role in sensory hypersensitivity and pathological pain. We found that the ischemia-simulating medium induced large inward currents in dorsal horn neurons recorded. The onset of the ischemia-induced inward currents was age-dependent, being onset earlier in older animals. Increases of sensory input by the stimulation of afferent fibers with electrical impulses or by capsaicin significantly speeded up the onset of the ischemia-induced inward currents. The ischemia-induced inward currents were abolished by the glutamate receptor antagonists CNQX (20 μM) and APV (50 μM). The ischemia-induced inward currents were also substantially inhibited by the glutamate transporter inhibitor TBOA (100 μM). Our results suggest that ischemia caused reversal operation of glutamate transporters, leading to the release of glutamate via glutamate transporters and the subsequent activation of glutamate receptors in the spinal dorsal horn neurons

A P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord

Of the six lamina regions in the dorsal horn of the spinal cord, lamina I is a major sensory region involved in nociceptive transmission under both physiological and pathological conditions. While P2X receptors have been shown to be involved in nociception, it remains unknown if P2X receptors are involved in nociceptive transmission to lamina I neurons. Using rat spinal cord slice preparations and patch-clamp recordings, we have demonstrated that the excitatory synaptic transmission between primary afferent fibers and lamina I neurons is significantly affected by ATP and α,β-methylene-ATP. The synaptic effects of them include the increases of the frequency of both miniature excitatory postsynaptic currents (mEPSCs) and spontaneous EPSCs (sEPSCs), and decreases of evoked EPSCs (eEPSCs). These effects were blocked by pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS, 10 μM) and suramin (30 μM). In the neurons for which ATP and α,β-methylene-ATP had effects on mEPSCs, sEPSCs and eEPSCs, capsaicin produced similar synaptic effects. Our results indicate that P2X receptors are expressed on many afferent fibers that directly synapse to lamina I neurons. Furthermore, these P2X receptor-expressing afferent fibers are capsaicin-sensitive nociceptive afferents. Thus, this study reveals a P2X receptor-mediated nociceptive afferent pathway to lamina I of the spinal cord and provides a new insight into the nociceptive functions of P2X receptors

Substance P-driven feed-forward inhibitory activity in the mammalian spinal cord

In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets

Are voltage-gated sodium channels on the dorsal root ganglion involved in the development of neuropathic pain?

Neuropathic pain is a common clinical condition. Current treatments are often inadequate, ineffective, or produce potentially severe adverse effects. Understanding the mechanisms that underlie the development and maintenance of neuropathic pain will be helpful in identifying new therapeutic targets and developing effective strategies for the prevention and/or treatment of this disorder. The genesis of neuropathic pain is reliant, at least in part, on abnormal spontaneous activity within sensory neurons. Therefore, voltage-gated sodium channels, which are essential for the generation and conduction of action potentials, are potential targets for treating neuropathic pain. However, preclinical studies have shown unexpected results because most pain-associated voltage-gated channels in the dorsal root ganglion are down-regulated after peripheral nerve injury. The role of dorsal root ganglion voltage-gated channels in neuropathic pain is still unclear. In this report, we describe the expression and distribution of voltage-gated sodium channels in the dorsal root ganglion. We also review evidence regarding changes in their expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. We finally discuss their potential involvement in neuropathic pain

P2X receptor-mediated purinergic sensory pathways to the spinal cord dorsal horn

P2X receptors are expressed on different functional groups of primary afferent fibers. P2X receptor-mediated sensory inputs can be either innocuous or nociceptive, depending on which dorsal horn regions receive these inputs. We provide a brief review of P2X receptor-mediated purinergic sensory pathways to different regions in the dorsal horn. These P2X purinergic pathways are identified in normal animals, which provides insights into their physiological functions. Future studies on P2X purinergic pathways in animal models of pathological conditions may provide insights on how P2X receptors play a role in pathological pain states

Geochemistry of soil gas in the seismic fault zone produced by the Wenchuan Ms 8.0 earthquake, southwestern China

The spatio-temporal variations of soil gas in the seismic fault zone produced by the 12 May 2008 Wenchuan Ms 8.0 earthquake were investigated based on the field measurements of soil gas concentrations after the main shock. Concentrations of He, H2, CO2, CH4, O2, N2, Rn, and Hg in soil gas were measured in the field at eight short profiles across the seismic rupture zone in June and December 2008 and July 2009. Soil-gas concentrations of more than 800 sampling sites were obtained. The data showed that the magnitudes of the He and H2 anomalies of three surveys declined significantly with decreasing strength of the aftershocks with time. The maximum concentrations of He and H2 (40 and 279.4 ppm, respectively) were found in three replicates at the south part of the rupture zone close to the epicenter. The spatio-temporal variations of CO2, Rn, and Hg concentrations differed obviously between the north and south parts of the fault zone. The maximum He and H2 concentrations in Jun 2008 occurred near the parts of the rupture zone where vertical displacements were larger. The anomalies of He, H2, CO2, Rn, and Hg concentrations could be related to the variation in the regional stress field and the aftershock activity

Prevalence of cardiovascular disease and risk factors in a rural district of Beijing, China: a population-based survey of 58,308 residents

Abstract Background Cardiovascular disease (CVD) is the leading cause of global disease burden. Although stroke was thought to be more prevalent than coronary heart disease (CHD) in Chinese, the epidemic pattern might have been changed in some rural areas nowadays. This study was to estimate up-to-date prevalence of CVD and its risk factors in rural communities of Fangshan District, Beijing, China. Methods A cross-sectional population survey was carried out by stratified cluster sampling. A total of 58,308 rural residents aged over 40 years were surveyed by face-to-face interview and physical examination during 2008 and 2010. The standardized prevalence was calculated according to adult sample data of China's 5th Population Census in 2000, and the adjusted prevalence odds ratio (POR) was calculated for the association of CHD/stroke with its cardiovascular risk factors in multivariate logistic regression models. Results Age- and sex-standardized prevalence was 5.6% for CHD (5.2% in males and 5.9% in females), higher than the counterpart of 3.7% (4.7% in males and 2.6% in females) for stroke. Compared with previous studies, higher prevalence of 7.7%, 47.2%, 53.3% in males and 8.2%, 44.8%, 60.7% in females for diabetes, hypertension and overweight/obesity were presented accordingly. Moreover, adjusted POR (95% confidence interval) of diabetes, obesity, stage 1 and stage 2 hypertension for CHD as 2.51 (2.29 to 2.75), 1.53 (1.38 to 1.70), 1.13 (1.02 to 1.26) and 1.35 (1.20 to 1.52), and for stroke as 2.24 (1.98 to 2.52), 1.25 (1.09 to 1.44), 1.44 (1.25 to 1.66) and 1.70 (1.46 to 1.98) were shown respectively in the multivariate logistic regression models. Conclusions High prevalence of CVD and probably changed epidemic pattern in rural communities of Beijing, together with the prevalent cardiovascular risk factors and population aging, might cause public health challenges in rural Chinese population