Friese N, Diop L, Chevalier E, Angel F, Rivière P J, Dahl S G
Institut de Recherche Jouveinal, Fresnes, France.
Regul Pept. 1997 May 14;70(1):1-7. doi: 10.1016/s0167-0115(97)02141-1.
This study investigates the contribution of prostaglandins (PG) and calcitonin gene-related peptide (CGRP) pathways in visceral pain induced by peritoneal irritation in rats. Peritoneal irritation was produced by i.p. administration of acetic acid (AA: 0.06-1.0%, 10 ml/kg). Visceral pain was scored by counting abdominal contractions. The effect of CGRP (3-100 microg/kg, i.p.) was also evaluated. Like AA, CGRP induced abdominal pain. Neonatal pretreatment with capsaicin reduced abdominal contractions produced by AA (0.6%) and CGRP (20 microg/kg) with 64.6% and 45.6%, respectively. Abdominal contractions induced by AA and CGRP were blocked by two antinociceptive drugs, mu-and kappa-opioid agonists, morphine and (+/-)-U-50,488H, respectively. Indomethacin (3 mg/kg, s.c.) reduced the number of abdominal contractions produced by AA by 78.1%+/-6.4% but did not inhibit abdominal contractions produced by CGRP. The CGRP, receptor antagonist, hCGRP(8-37) (300 microg/kg, i.v.) inhibited AA- and CGRP-induced abdominal contractions with 57.5%+/-12.4% and 51.6%+/-11.3%, respectively. Concomitant i.p. administration of PGE1 and PGE2 (0.3 mg/kg of each) produced abdominal contractions which were inhibited 45.6%+/-9.3% by hCGRP(8-37) (300 microg/kg i.v.). Taken together, these results suggest that peritoneal irritation is likely to trigger the release of prostaglandins, which in turn produces a release of CGRP from primary sensory afferents.
本研究调查了前列腺素（PG）和降钙素基因相关肽（CGRP）通路在大鼠腹膜刺激诱导的内脏痛中的作用。通过腹腔注射乙酸（AA：0.06 - 1.0%，10 ml/kg）产生腹膜刺激。通过计数腹部收缩来对内脏痛进行评分。还评估了CGRP（3 - 100 μg/kg，腹腔注射）的作用。与AA一样，CGRP也诱导腹痛。新生大鼠用辣椒素预处理可分别减少由AA（0.6%）和CGRP（20 μg/kg）引起的腹部收缩，减少率分别为64.6%和45.6%。由AA和CGRP诱导的腹部收缩分别被两种抗伤害感受药物——μ和κ阿片类激动剂吗啡和（±）-U - 50,488H阻断。吲哚美辛（3 mg/kg，皮下注射）使由AA引起的腹部收缩次数减少78.1%±6.4%，但不抑制由CGRP引起的腹部收缩。CGRP受体拮抗剂hCGRP（8 - 37）（300 μg/kg，静脉注射）分别抑制由AA和CGRP诱导的腹部收缩，抑制率分别为57.5%±12.4%和51.6%±11.3%。腹腔同时注射PGE1和PGE2（各0.3 mg/kg）可引起腹部收缩，hCGRP（8 - 37）（300 μg/kg静脉注射）可抑制45.6%±9.3%。综上所述，这些结果表明腹膜刺激可能触发前列腺素的释放，进而导致初级感觉传入神经释放CGRP。
