Microglial activation of p38 contributes to scorpion envenomation-induced hyperalgesia.
Intraplantar (i.pl.) injection of BmK I, a receptor site 3-specific modulator of voltage-gated sodium channels (VGSCs) from the venom of scorpion Buthus martensi Karsch (BmK), was shown to induce long-lasting and spontaneous nociceptive responses as demonstrated through experiments utilizing primary thermal and mirror-imaged mechanical hypersensitivity with different time course of development in rats. In this study, microglia was activated on both sides of L4-L5 spinal cord by i.pl. injection of BmK I. Meanwhile, the activation of p38/MAPK in L4-L5 spinal cord was found to be co-expressed with OX-42, the cell marker of microglia. The unilateral thermal and bilateral mechanical pain hypersensitivity of rat induced by BmK I was suppressed in a dose-dependent manner following pretreatment with SB203580 (a specific inhibitor of p-p38). Interestingly, microglia activity was also reduced in the presence of SB203580, which suggests that BmK I-induced microglial activation is mediated by p38/MAPK pathway. Combined with previously published literature, the results of this study demonstrate that p38-dependent microglial activation plays a role in scorpion envenomation-induced pain-related behaviors.
Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, PR China.
Qing-Shan
QS
Niu
Feng
F
Jiang
Li-Ming
LM
Hua
Jin
J
Fu
Yun-Lu
YL
Jiao
Yong-Hua
YH
Ji
Gang
G
Ding
D000818:Animals; D001522:Behavior, Animal; D006930:Hyperalgesia / Q000139:chemically induced* / Q000201:enzymology* / Q000523:psychology; D007093:Imidazoles / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D017628:Microglia / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007093:Imidazoles; D011725:Pyridines; D012604:Scorpion Venoms; C105338:makatoxin I; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
BmK I; Microglia; Pain; p38