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We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 receptors. In Na(v)1.9-/- mice, the(More)
The differential distribution of two tetrodotoxin resistant (TTXr) voltage-gated sodium channels SNS (PN3) and SNS2 (NaN) in rat primary sensory neurons has been investigated. Both channels are sensory neuron specific with SNS2 restricted entirely to those small dorsal root ganglion (DRG) cells with unmyelinated axons (C-fibers). SNS, in contrast, is(More)
Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting(More)
Brain-derived neurotrophic factor (BDNF) is expressed in nociceptive sensory neurons and transported anterogradely to the dorsal horn of the spinal cord where it is located in dense core vesicles in C-fiber terminals. Peripheral inflammation substantially up-regulates BDNF mRNA and protein in the dorsal root ganglion (DRG) in a nerve growth factor-dependent(More)
Vanilloid receptor 1 (VR1) is essential to the development of inflammatory hyperalgesia. We investigated whether inflammation can increase in VR1 positive neuronal profiles in rat DRG neurons using histochemical methods. We also used size frequency analysis and double staining with several neuronal markers to investigate whether or not inflammation alters(More)
The transient receptor potential ion channel, TRPV1 plays an essential role in the development of inflammatory thermal hyperalgesia. We investigated the dependence of inflammatory TRPV1 induction on neurotrophic factor. Rat dorsal root ganglia (DRG) neurons were classified according to immunostaining for trk-A and IB4 and the effects of antibodies against(More)
Cannabinoids act on various regions in the nervous system to modulate neuronal activity including nociception. Here, we investigated CB1 receptor expression in primary afferent neurons in the dorsal root ganglion (DRG) and the efficacy of a local (intraplantar) application of the selective CB1 agonist, 2-arachidonyl-2-chloroethylamide (ACEA), on(More)
A cardinal feature of inflammation is heightened pain sensitivity at the site of the inflamed tissue. This results from the local release by immune and injured cells of nociceptor sensitizers, including prostaglandin E(2), bradykinin, and nerve growth factor, that reduce the threshold and increase the excitability of the peripheral terminals of nociceptors(More)
The acute respiratory distress syndrome (ARDS) is a disease process that is characterized by diffuse inflammation in the lung parenchyma and resultant permeability edema. The involvement of inflammatory mediators in ARDS has been the subject of intense investigation, and oxidant-mediated tissue injury is likely to be important in the pathogenesis of ARDS.(More)
Bradykinin, an inflammatory mediator, sensitizes nociceptor peripheral terminals reducing pain threshold. We now show that the B2 kinin receptor is expressed in rat dorsal horn neurons and that bradykinin, a B2-specific agonist, augments AMPA- and NMDA-induced, and primary afferent-evoked EPSCs, and increases the frequency and amplitude of miniature EPSCs(More)