Electrocorticographic desynchronization after application of visceral and somatic noxious stimuli in urethane-anesthetized rats: effect of intrathecal administration of tachykinin (NK 1 or NK 2) receptor antagonists.
We investigated the electrocortical (E.Co.G) correlates of visceral (topical capsaicin application or overdistension of the urinary bladder) and somatic (perineal pinching) painful stimulation in urethane-anesthetized rats and their modulation by intrathecal application of selective tachykinins receptors (NK 1 and NK 2) antagonists. Vesical overdistension or topical capsaicin on the bladder serosal surface produced an immediate and lasting E.Co.G. desynchronization resembling a cortical arousal. A second application of capsaicin was ineffective. Bladder contraction induced by topical acetylcholine did not alter E.Co.G. A desynchronized E.Co.G. was also induced by pinching of the perineal area of the rat. Intrathecal administration of lidocaine at lumbosacral level abolished the E.Co.G. desynchronization induced by both visceral and somatic noxious stimulation. On the other hand capsaicin-induced or over-distension (but not pinching-induced) E.Co.G. desynchronization disappeared in animals systemically pretreated with capsaicin or after intrathecal administration of NK 1 tachykinin receptor antagonists such as the peptide GR 82334 or the nonpeptide RP 67580, whereas the inactive enantiomer RP 68651 or the nonpeptide NK 2 antagonists SR 48968 were ineffective. In conclusion, the experimental model described herein, allowing a quantitative analysis of the E.Co.G. correlates of visceral and somatic noxious stimulation in urethane-anesthetized rats, provides evidence for a specific neural pathway carrying bladder-arising visceral (both mechanical and chemical) nociception that uses pelvic capsaicin-sensitive afferents projecting to NK 1 (but not NK 2) bearing spinal neurons and that ultimately leads to activation of cortical areas.
Conte
B
B
Menarini Ricerche Sud, Pharmacology Department, Pomezia, Roma, Italy.
Cutrufo
C
C
Manzini
S
S
D000109:Acetylcholine / Q000633:toxicity; D000287:Administration, Topical; D000758:Anesthesia; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002211:Capsaicin / Q000633:toxicity; D003344:Cortical Synchronization / Q000187:drug effects*; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology*; D007278:Injections, Spinal; D054833:Isoindoles; D008012:Lidocaine; D008297:Male; D010502:Perineum / Q000294:innervation / Q000502:physiology; D010803:Physalaemin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012680:Sensitivity and Specificity; D014520:Urethane; D001743:Urinary Bladder / Q000294:innervation
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D010880:Piperidines; D018039:Receptors, Tachykinin; C079014:GR 82334; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D010803:Physalaemin; D014520:Urethane; C073839:SR 48968; D008012:Lidocaine; D000109:Acetylcholine; D002211:Capsaicin