Different roles of spinal p38 and c-Jun N-terminal kinase pathways in bee venom-induced multiple pain-related behaviors.
Our previous studies have established the idea that different types of pain induced by subcutaneous bee venom (BV) injection might be mediated by different spinal signaling pathways. To further testify this hypothesis, the present investigation was designed to detect whether spinal p38 and c-Jun N-terminal kinase (JNK) pathways are equally or differentially involved in the development of persistent spontaneous nociception (PSN), primary heat and mechanical hyperalgesia, and mirror-image heat (MIH) hypersensitivity in the BV model, by evaluating the effects of intrathecal (i.t.) pre-administration of a p38 inhibitor SB239063 and a JNK inhibitor SP600125 in the conscious rat. The results showed that i.t. pre-treatment with either SB239063 or SP600125 caused a significant prevention of BV-induced persistent paw flinching reflex in a dose-related manner, with the former exhibiting much stronger inhibition than the latter. Moreover, the same doses of SB239063 and SP600125 also exhibited different suppressive actions on the induction of primary heat hyperalgesia and MIH hypersensitivity. That is, SP600125 produced a larger increase of thermal latency than SB239063 in the injected paw, whereas SB239063 mainly affected the value measured in the non-injected paw. Pre-treatment with neither SB239063 nor SP600125 had any effect on BV-evoked mechanical hyperalgesia. Taken together, these data suggest that activation of p38 in the spinal cord preferentially contributes to the development of PSN and MIH hypersensitivity under pathological state, while spinal JNK signaling pathways might play more important roles in inducing primary heat hyperalgesia.
Cao
Fa-Le
FL
Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
Liu
Ming-Gang
MG
Hao
Jian
J
Li
Zhen
Z
Lu
Zhuo-Min
ZM
Chen
Jun
J
D000344:Afferent Pathways / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D001514:Bee Venoms; D004791:Enzyme Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases