Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats.
OBJECTIVE
There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model.


METHODS
Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 mumol x L(-1), 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed.


RESULTS
Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P < 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P < 0.05).


CONCLUSIONS
Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed.
Liou
Jiin-Tarng
JT
Department of Anesthesiology, Chang Gung Memorial Hospital, Gueishan, Taoyuan 333, Taiwan. ani123@adm.cgmh.org.tw
Liu
Fu-Chao
FC
Mao
Chih-Chieh
CC
Hsin
Shi-Tai
ST
Lui
Ping-Wing
PW
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D000225:Adenine