scholarly journals Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse

2017 ◽  
Vol 117 (1) ◽  
pp. 251-259 ◽  
Author(s):  
T. Akiyama ◽  
M. Nagamine ◽  
A. Davoodi ◽  
M. Ivanov ◽  
M. Iodi Carstens ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Ganglion Cells ◽  
Underlying Mechanism ◽  
Intradermal Injection ◽  
Evoked Responses ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Temperature Controlled

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.

Five Sources of a Dorsal Root Potential: Their Interactions and Origins in the Superficial Dorsal Horn

1997 ◽  
Vol 78 (2) ◽  
pp. 860-871 ◽  
Author(s):  
Patrick D. Wall ◽  
Malcolm Lidierth
Keyword(s):  
Motor Cortex ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Repetitive Stimulation ◽  
Superficial Dorsal Horn ◽  
Dorsal Horn Neurons ◽  
Dorsal Roots ◽  
Myelinated Fibers ◽  
Root Potential ◽  
Stimulation Of

Wall, Patrick D. and Malcolm Lidierth. Five sources of a dorsal root potential: their interactions and origins in the superficial dorsal horn. J. Neurophysiol. 78: 860–871, 1997. The dorsal root potential (DRP) was measured on the lumbar dorsal roots of urethan anesthetized rats and evoked by stimulation of five separate inputs. In some experiments, the dorsal cord potential was recorded simultaneously. Stimulation of the L3 dorsal root produced a DRP on the L2 dorsal root containing the six components observed in the cat including the prolonged negative wave (DRP V of Lloyd 1952 ). A single shock to the myelinated fibers in the sural nerve produced a DRP on the L6 dorsal root after the arrival in the cord of the afferent volley. The shape of this DRP was similar to that produced by dorsal root stimulation. Repetitive stimulation of the myelinated fibers in the gastrocnemius nerve also produced a prolonged negative DRP on the L6 dorsal root. When a single stimulus (<5 μA; 200 μs) was applied through a microelectrode to the superficial Lissauer Tract (LT) at the border of the L2 and L3 spinal segments, a characteristic prolonged negative DRP (LT-DRP) began on the L2 dorsal root after some 15 ms. Stimulation of the LT evoked DRPs bilaterally. Recordings on nearby dorsal roots showed this DRP to be unaccompanied by stimulation of afferent fibers in those roots. The LT-DRP was unaffected by neonatal capsaicin treatment that destroyed most unmyelinated fibers. Measurements of myelinated fiber terminal excitability to microstimulation showed that the LT-DRP was accompanied by primary afferent depolarization. Repetitive stimulation through a microelectrode in sensorimotor cortex provoked a prolonged and delayed negative DRP (recorded L2–L4). Stimulation in the cortical arm area and recording on cervical dorsal roots showed that the DRP was evoked more from motor areas than sensory areas of cortex. Interactions were observed between the LT-DRP and that evoked from the sural or gastrocnemius nerves or motor cortex. The LT-DRP was inhibited by preceding stimulation of the other three sources but LT stimulation did not inhibit DRPs evoked from sural or gastrocnemius nerves on the L6 dorsal root or from motor cortex on the L3 root. However, LT stimulation did inhibit the DRP evoked by a subsequent Lissaeur tract stimulus. Recordings were made from superficial dorsal horn neurons. Covergence of input from LT sural, and gastrocnemius nerves and cortex was observed. Spike-triggered averaging was used to examine the relationship between the ongoing discharge of superficial dorsal horn neurons and the spontaneous DRP. The discharge of 81% of LT responsive cells was correlated with the DRP.

L1 CAM expression in the superficial dorsal horn is derived from the dorsal root ganglion

2005 ◽  
Vol 485 (4) ◽  
pp. 267-279 ◽  
Author(s):  
Stephen A. Runyan ◽  
Roland Roy ◽  
Hui Zhong ◽  
Patricia E. Phelps
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Superficial Dorsal Horn

scholarly journals Excitation of Mouse Superficial Dorsal Horn Neurons by Histamine and/or PAR-2 Agonist: Potential Role in Itch

2009 ◽  
Vol 102 (4) ◽  
pp. 2176-2183 ◽  
Author(s):  
Tasuku Akiyama ◽  
Mirela Iodi Carstens ◽  
E. Carstens
Keyword(s):  
Dorsal Horn ◽  
Potential Role ◽  
Dynamic Range ◽  
Intradermal Injection ◽  
Mustard Oil ◽  
Superficial Dorsal Horn ◽  
Noxious Heat ◽  
Dorsal Horn Neurons ◽  
Sensory Pathways ◽  
Transduction Mechanisms

Recent studies have suggested the existence of separate transduction mechanisms and sensory pathways for histamine and nonhistaminergic types of itch. We studied whether histamine and an agonist of the protease-activated receptor (PAR)-2, associated with nonhistaminergic itch, excite murine dorsal horn neurons. Single units were recorded in superficial lumbar dorsal horn of adult ICR mice anesthetized with pentobarbital. Unit activity was searched using a small intradermal hindpaw injection of histamine or the PAR-2 agonist SLIGRL-NH2. Isolated units were subsequently challenged with intradermal histamine followed by SLIGRL-NH2 (each 50 μg/1 μl) or reverse order, followed by mechanical, thermal, and algogenic stimuli. Forty-three units were classified as wide dynamic range (62%), nociceptive specific (22%), or mechano insensitive (16%). Twenty units gave prolonged (mean, 10 min) discharges to intradermal injection of histamine; 76% responded to subsequent SLIGRL-NH2, often more briefly. Units additionally responded to noxious heat (63%), cooling (43%), topical mustard oil (53%), and intradermal capsaicin (67%). Twenty-two other units gave prolonged (mean, 5 min) responses to initial intradermal injection of SLIGRL-NH2; 85% responded to subsequent intradermal histamine. They also responded to noxious heat (75%), mustard oil (93%), capsaicin (63%), and one to cooling. Most superficial dorsal horn neurons were excited by both histamine and the PAR-2 agonist, suggesting overlapping pathways for histamine- and non–histamine-mediated itch. Because the large majority of pruritogen-responsive neurons also responded to noxious stimuli, itch may be signaled at least partly by a population code.

Local Anesthetic Inhibition of Voltage-activated Potassium Currents in Rat Dorsal Root Ganglion Neurons

2001 ◽  
Vol 94 (6) ◽  
pp. 1089-1095 ◽  
Author(s):  
Hirochika Komai ◽  
Thomas S. McDowell
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Local Anesthetic ◽  
Local Anesthetics ◽  
Dorsal Root ◽  
Drg Neurons ◽  
Dorsal Horn Neurons ◽  
K Currents

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.

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