Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.
BACKGROUND
A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology.


METHODS
An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+(BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined.


RESULTS
The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCachannels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors.


CONCLUSIONS
These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai, 200436, People's Republic of China.
Zheng-Wei
ZW
Li
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai, 200436, People's Republic of China.
Bin
B
Wu
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai, 200436, People's Republic of China.
Pin
P
Ye
Department of Pharmacology and Toxicology and Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA. zt2@iupui.edu.
Zhi-Yong
ZY
Tan
Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai, 200436, People's Republic of China. yhji@staff.shu.edu.cn.
Yong-Hua
YH
Ji
D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D009437:Neuralgia / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D013116:Spinal Cord / Q000378:metabolism*
D012604:Scorpion Venoms; D015222:Sodium Channels; C105338:makatoxin I; D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A
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