scholarly journals Chronic pregabalin inhibits synaptic transmission between rat dorsal root ganglion and dorsal horn neurons in culture

Channels ◽  
2012 ◽  
Vol 6 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Janek Hendrich ◽  
Claudia S. Bauer ◽  
Annette C. Dolphin
2001 ◽  
Vol 94 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hirochika Komai ◽  
Thomas S. McDowell

Background Local anesthetic actions on the K+ channels of dorsal root ganglion (DRG) and dorsal horn neurons may modulate sensory blockade during neuraxial anesthesia. In dorsal horn neurons, local anesthetics are known to inhibit transient but not sustained K+ currents. The authors characterized the effects of local anesthetics on K+ currents of isolated DRG neurons. Methods The effects of lidocaine, bupivacaine, and tetracaine on K+ currents in isolated rat DRG neurons were measured with use of a whole cell patch clamp method. The currents measured were fast-inactivating transient current (I(Af)), slow-inactivating transient current (I(As)), and noninactivating sustained current (I(Kn)). Results One group of cells (type 1) expressed I(Af) and I(Kn). The other group (type 2) expressed I(As) and I(Kn). The diameter of type 2 cells was smaller than that of type 1 cells. Lidocaine and bupivacaine inhibited all three K+ currents. Tetracaine inhibited I(As) and I(Kn) but not I(Af) For bupivacaine, the concentration for half-maximal inhibition (IC50) of I(Kn) in type 2 cells was lower than that for I(Kn) in type 1 cells (57 vs. 121 microM). Similar results were obtained for tetracaine (0.6 vs. 1.9 mM) and for lidocaine (2.2 vs. 5.1 mM). Conclusions Local anesthetics inhibited both transient and sustained K+ currents in DRG neurons. Because K+ current inhibition is known to potentiate local anesthetic-induced impulse inhibition, the lower IC50 for I(Kn) of small type 2 cells may reflect preferential inhibition of impulses in nociceptive neurons. The overall modulatory actions of local anesthetics probably are determined by their differential effects on presynaptic (DRG) and postsynaptic (dorsal horn neurons) K+ currents.


2017 ◽  
Vol 117 (1) ◽  
pp. 251-259 ◽  
Author(s):  
T. Akiyama ◽  
M. Nagamine ◽  
A. Davoodi ◽  
M. Ivanov ◽  
M. Iodi Carstens ◽  
...  

Itch is often triggered by warming the skin in patients with itchy dermatitis, but the underlying mechanism is largely unknown. We presently investigated if warming the skin enhances histamine- or serotonin (5-HT)-evoked itch behavior or responses of sensory dorsal root ganglion (DRG) cells, and if responses of superficial dorsal horn neurons to innocuous warming are enhanced by these pruritogens. In a temperature-controlled environmental chamber, mice exhibited greater scratching following intradermal injection of 5-HT, but not histamine, SLIGRL, or BAM8-22, when the skin surface temperature was above 36°C. Calcium imaging of DRG cells in a temperature-controlled bath revealed that responses to 5-HT, but not histamine, were significantly greater at a bath temperature of 35°C vs. lower temperatures. Single-unit recordings revealed a subpopulation of superficial dorsal horn neurons responsive to intradermal injection of 5-HT. Of these, 58% responded to innocuous skin warming (37°C) prior to intradermal injection of 5-HT, while 100% responded to warming following intradermal injection of 5-HT. Warming-evoked responses were superimposed on the 5-HT-evoked elevation in firing and were significantly larger compared with responses pre-5-HT, as long as 30 min after the intradermal injection of 5-HT. Five-HT-insensitive units, and units that either did or did not respond to intradermal histamine, did not exhibit any increase in the incidence of warmth sensitivity or in the mean response to warming following intradermal injection of the pruritogen. The results suggest that 5-HT-evoked responses of pruriceptors are enhanced during skin warming, leading to increased firing of 5-HT-sensitive dorsal horn neurons that signal nonhistaminergic itch. NEW & NOTEWORTHY Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.


1995 ◽  
Vol 7 (3) ◽  
pp. 427 ◽  
Author(s):  
S Rees ◽  
I Nitsos ◽  
J Rawson

A summary is presented of recently published studies on the structural and functional development of cutaneous and muscle receptors and the connections of their afferent fibres in fetal sheep (n = 26) aged between 67 and 143 days gestation (term, 146 days). In these studies it was shown that primary afferent fibres projected to, and made synaptic connections with, dorsal horn neurons in lumbosacral spinal cord by 56-61 days gestation. Sensory innervation of the skin occurred later by about 75 days gestation and, at this age, stimulation of the skin first activated cutaneous afferent fibres and evoked a discharge in dorsal root ganglion and dorsal horn neurons. Muscle stretch first activated muscle spindles and evoked a discharge in dorsal root ganglion cells by about 75 days. Prior to this (by about 67 days) primary afferent fibres had begun to innervate motoneuron pools in the spinal cord, and motor nerves had begun to innervate muscle fibres. Both muscle spindle and cutaneous innervation were relatively simple at mid gestation indicating that the structure of sensory receptors need not be complex in order to generate a response. Neural pathways necessary for reflex activity involving muscle spindles are therefore present and functional by mid gestation as are cutaneous pathways projecting from the skin to the spinal cord.


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