Phenotypes and peripheral mechanisms underlying inflammatory pain-related behaviors induced by BmK I, a modulator of sodium channels.
The integrated mechanisms of dynamic signaling of sodium channels involved in clinical pain are still not yet clear. In this study, a new rat inflammatory pain model was developed by using the unilateral intraplantar injection of BmK I, a receptor site 3-specific modulator of sodium channels from the venom of scorpion Buthus martensi Karsch (BmK). It was found that BmK I could induce several kinds of inflammatory pain-related behaviors including spontaneous pain companied with unique episodic paroxysms, primary thermal hypersensitivity, and mirror-image mechanical hypersensitivity with different time course of development, which could be suppressed by morphine, indomethacin, or bupivacaine to a different extent. The dramatic attenuation by pretreatment with resiniferatoxin (RTX), an ultrapotent analog of capsaicin, on BmK I-induced pain-related behaviors, paw edema, and spinal L4-L5 c-Fos expression demonstrated that capsaicin-sensitive primary afferent neurons played important roles in pain induced by BmK I. Furthermore, the electrophysiological recordings showed that BmK I persistently increased whole-cell and tetrodotoxin-resistant (TTX-R) peak sodium currents and significantly delayed the inactivation phase of whole-cell sodium currents but could not enhance capsaicin-evoked inward currents, in acute isolated small dorsal root ganglion neurons of rat. The results strongly suggested that the dynamic modulation of BmK I on sodium channels located in peripheral primary afferent neurons, especially in capsaicin-sensitive neurons, mediated pain sensation. Thus, BmK I may be a valuable pharmacological tool to understand the sodium channel-involved pain mechanisms.
Bai
Zhan-Tao
ZT
Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai, 200444, PR China. ztbai@yahoo.com.cn
Liu
Tong
T
Jiang
Feng
F
Cheng
Ming
M
Pang
Xue-Yan
XY
Hua
Li-Ming
LM
Shi
Jian
J
Zhou
Jing-Jing
JJ
Shu
Xue-Qin
XQ
Zhang
Jian-Wei
JW
Ji
Yong-Hua
YH
D000701:Analgesics, Opioid / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology*; D002045:Bupivacaine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000523:psychology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016760:Proto-Oncogene Proteins c-fos; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; C105338:makatoxin I; D009020:Morphine; D002211:Capsaicin; D007213:Indomethacin; D002045:Bupivacaine