scholarly journals Regulation of Peripheral Clock to Oscillation of Substance P Contributes to Circadian Inflammatory Pain

2012 ◽  
Vol 117 (1) ◽  
pp. 149-160 ◽  
Author(s):  
Jing Zhang ◽  
Huili Li ◽  
Huajing Teng ◽  
Ting Zhang ◽  
Yonglun Luo ◽  
...  
Keyword(s):  
Substance P ◽  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Inflammatory Pain ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Luciferase Assay ◽  
Nociceptive Response ◽  
Spinal Level ◽  
Spinal Dorsal

Background The daily fluctuations of many physiologic and behavioral parameters are differentially influenced by either central or peripheral clocks in mammals. Since substance P (SP) oscillates in some brain tissues and plays an indispensable role in modulating inflammatory pain at the spinal level, we speculated that SP mediates circadian nociception transmission at the spinal level. Methods In the present study behavioral observation, real-time polymerase chain reaction, luciferase assay, chromatin immunoprecipitation, and immunohistochemistry stain methods were used to investigate the role of SP in the spinal circadian nociception transmission and its regulation mechanism. Results Our results showed that under transcriptional regulation of BMAL1:CLOCK heterodimers, SP's coding gene Tac1 expression oscillates in dorsal root ganglion (n = 36), but not in the spinal dorsal horn. Further, the expression of SP cycled in the spinal dorsal horn, and this rhythmicity was potentially determined by circadian expression of Tac1 in dorsal root ganglion. Furthermore, the variation of SP expression induced by formalin was fluctuated in a similar rhythm to behavioral nociceptive response induced by formalin (n = 48); and the nociceptive behavioral circadian rhythm could be abolished through blockade of the SP-Neurokinin 1 receptor pathway (n = 70). Lastly, the variations of spinal SP expression and behavioral nociceptive response were in step, and both were changed by the deletion mutation of clock gene. Conclusions We conclude that spinal SP probably plays a pivotal role in modulating circadian inflammatory pain and suggest that peripheral circadian-regulated signaling is potentially an essential pathway for circadian nociceptive transmission.

miR-143 Regulated Inflammatory Pain by Target Rab1a in Spinal Dorsal Horn

2019 ◽  
Vol 11 (5) ◽  
pp. 670-677
Author(s):  
Cui Yin ◽  
Zhiyong Wang ◽  
Yubai Guo ◽  
Chao Ma ◽  
Wencan Han ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Inflammatory Pain ◽  
Messenger Rna ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Therapeutic Strategy ◽  
Nociceptive Neurons ◽  
Chronic Inflammatory Pain ◽  
Spinal Dorsal ◽  
Plastic Changes

Inflammation induces changes in nociceptive neurons which contribute to both peripheral and central sensitization of pain-sensitive pathways. Plastic changes in sensory neuron excitability are considered the cellular basis of persistent pain. It is well investigated that microRNA can modulate gene expression impact on pain. It has reported miR-143 was downregulated in dorsal root ganglion (DRG) in inflammatory mice. However, less information is available about contribution of miRNA in pain behavior. Here, we demonstrate that miR-143 is also downregulated in spinal dorsal horn. Local increase of miR-143 by using an miR-143 mimic can suppress established inflammatory pain. Furthermore, block miR-143 function was sufficient to cause pain-related behaviors in intact mice. miR-143 targeted the Rab1a gene, and decreased miR-143 associated with pain caused increased Rab1a protein expression, independent of messenger RNA levels. Consistently, miR-143 overexpression in spinal cord suppressed increased Rab1a expression and normalized long-lasting hyperexcitability of nociceptive neurons. These findings demonstrate miR-143 downregulation is causally involved in maintenance of inflammatory pain through regulation of Rab1a and miR-143 supplement offers a novel therapeutic strategy specific for chronic inflammatory pain.

scholarly journals L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons

2020 ◽  
Vol 134 (1) ◽  
pp. 88-102
Author(s):  
Daisuke Uta ◽  
Kohei Koga ◽  
Hidemasa Furue ◽  
Keiji Imoto ◽  
Megumu Yoshimura
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Dorsal Root Ganglion Neurons ◽  
Evoked Responses ◽  
Half Maximum ◽  
Sodium Currents ◽  
Spinal Dorsal ◽  
Ganglion Neurons

Background Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified. Methods The authors performed electrophysiologic analysis on rat dorsal root ganglion neurons in vitro and on spinal transmissions in vivo. Results In the dorsal root ganglion, these anesthetics decreased the amplitudes of action potentials. The half-maximum inhibitory concentrations of D-enantiomer D-bupivacaine were almost equal for Aβ (29.5 μM), Aδ (29.7μM), and C (29.8 μM) neurons. However, the half-maximum inhibitory concentrations of L-bupivacaine was lower for Aδ (19.35 μM) and C (19.5 μM) neurons than for A β (79.4 μM) neurons. Moreover, D-bupivacaine almost equally inhibited tetrodotoxin-resistant (mean ± SD: 15.8 ± 10.9% of the control, n = 14, P < 0.001) and tetrodotoxin-sensitive (15.4 ± 15.6% of the control, n = 11, P = 0.004) sodium currents. In contrast, L-bupivacaine suppressed tetrodotoxin-resistant sodium currents (26.1 ± 19.5% of the control, n = 18, P < 0.001) but not tetrodotoxin-sensitive sodium currents (74.5 ± 18.2% of the control, n = 11, P = 0.477). In the spinal dorsal horn, L-bupivacaine decreased the area of pinch-evoked excitatory postsynaptic currents (39.4 ± 11.3% of the control, n = 7, P < 0.001) but not touch-evoked responses (84.2 ± 14.5% of the control, n = 6, P = 0.826). In contrast, D-bupivacaine equally decreased pinch- and touch-evoked responses (38.8 ± 9.5% of the control, n = 6, P = 0.001, 42.9 ± 11.8% of the control, n = 6, P = 0.013, respectively). Conclusions These results suggest that the L-enantiomer of bupivacaine (L-bupivacaine) effectively inhibits noxious transmission to the spinal dorsal horn by blocking action potential conduction through C and Aδ afferent fibers. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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