Involvement of hypogastric and pelvic nerves for conveying cystitis induced nociception in conscious rats.
OBJECTIVE
We determined the sites of the antinociceptive action of morphine in the experimental model of cyclophosphamide induced cystitis and investigated the afferent nerve fibers involved in nociception transmission originating from the bladder.


METHODS
Cyclophosphamide (200 mg./kg.) given intraperitoneally was used to induce cystitis in male rats and their behavior was observed and scored. The effect of 2 mg./kg. systemic morphine given intravenously on cyclophosphamide induced behavioral modifications was tested when administered alone and after 100 microg. naloxone per rat given intrathecally at the L1 to L2 or L6 to S1 level. The spinal antinociceptive effect of morphine was also tested when administered intrathecally alone at 10, 100 and 200 microg. per rat at L1 to L2, alone at 100 microg. per rat at L1 to L2 or L6 to S1, alone at 100 microg. per rat at L1 to L2 and L6 to S1 simultaneously, alone at 200 microg. per rat at L1 to L2 and after 100 microg. naloxone per rat given intrathecally at L6 to S1 at 100 microg. per rat at L1 to L2.


RESULTS
Cyclophosphamide induced marked modifications in the behavior of the rats, including a decreased breathing rate, eye closing and specific postures. Morphine given intravenously reversed these behavioral disorders and this reversal was completely prevented by pretreatment with intrathecal naloxone. A dose of 100 microg. per rat given intrathecally also reversed these behavioral disorders by about 25% at the L1 to L2 and L6 to S1 levels. In addition, a dose of 100 microg. morphine per rat administered intrathecally and simultaneously at L1 to L2 and L6 to S1 produced an effect equal to the sum of those observed when administered separately, that is about 50%, whereas morphine at an intrathecal dose of 200 microg. at L1 to L2 produced the same effect as 100 microg. given intrathecally at the same level or at L6 to S1 (25%). Also, 100 microg. naloxone per rat administered intrathecally at L6 to S1 prevented the effect of 100 microg. morphine at L1 to L2.


CONCLUSIONS
These results confirm the previously reported antinociceptive effect of systemic morphine in this model of cyclophosphamide cystitis, suggest that this antinociceptive action is completely located at the spinal site and most importantly demonstrate by the pharmacological approach and behavioral analysis that nociceptive sensations originating from the bladder are conveyed by hypogastric and pelvic nerves in this cyclophosphamide cystitis model in the conscious rat.
Meen
M
M
INSERM EPI 9904, Laboratoire de Physiologie, Faculté de Pharmacie, Clermont-Ferrand Cedex, France.
Coudore-Civiale
M A
MA
Eschalier
A
A
Boucher
M
M
D000818:Animals; D003243:Consciousness; D003520:Cyclophosphamide; D003556:Cystitis / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D007001:Hypogastric Plexus / Q000503:physiopathology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000209:etiology* / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*
D009270:Naloxone; D009020:Morphine; D003520:Cyclophosphamide