中文摘要：

观察椎管内注射感觉神经元特异性受体选择性激动剂牛肾上腺髓质8—22肽（bovine adrenal medulla 8-22，BAM8．22）在福尔马林引起的持续性痛中对吗啡耐受的影响．结果表明，吗啡（20μg）在正常大鼠中能显著抑制福尔马林引起的痛行为，多次应用吗啡导致耐受后，其抑制痛行为的能力大大减弱（P〈0．001）；吗啡耐受后，BAM8-22（0．1nm01）能翻转吗啡的耐受效应，福尔马林引起第2期抬足／舔爪持续时间和抖动次数分别减少了39．4％（P〈0．001）和25．3％（P〈0．05）．每天椎管内联合应用BAM8—22（0．1nm01）和吗啡（20μg）不影响吗啡耐受的形成，但隔天给予BAM8-22则能有效延缓吗啡耐受的形成，福尔马林引起第2期缩足舔爪和抖动分别为14．7min和234．5次，与吗啡耐受鼠相比，分别减少了41．0％（P〈0．001）和24．8％（P〈0．05）．然而，BAM8-22并没有完全翻转或抑制吗啡的耐受（P〈0．001）．此外，连续6d给予BAM8-22后会降低吗啡在福尔马林持续痛中的抗伤害作用．证明在福尔马林引起的持续性痛中，SNSR受体参与了调制阿片受体的敏感性．同时，提示在持续性痛中，通过BAM8-22延缓或翻转吗啡耐受是利用阿片受体治疗持续性痛的有效方法．

英文摘要：

The present study was designed to investigate the effects of bovine adrenal medulla 8-22 （ BAM8-22）, an selective agonist of sensory neuron-specific receptor （ SNSR）, on morphine tolerance in formalin-induced persistent pain. Intrathecal （ i. t. ） administration of morphine （20 ~xg） markedly inhibited formalin-evoked lifting/licking and flinching behaviors in naive rats, but this in- hibition effect remarkably lower in morphine tolerance when morphine was administrated i. t. for 7 days （P 〈 0. 001） . Pretreatment i. t. with BAM8-22 （0. 1 nmol） evidently reversed established morphine tolerance. Formalin-induced the time of lifting/licking and the number of flinches were re- spectively decrease 39.4% （P 〈 0. 001 ） and 25.3% （P 〈 0. 05） in second phase in formalin test, compared with morphine in tolerant rats. Co-administration of BAM8-22 （0. 1 nmol ） daily with morphine did not inhibit the development of morphine tolerance, but Co-administration of BAM8-22 （0. 1 nmol） every other day, but not daily, with morphine remarkably attenuated the development of morphine tolerance. The time of lifting/licking and the number of flinches were respectively decrease 41.0% （P 〈 0. 001 ） and 24.8% （P 〈 0.05） in second phase compared with morphine in tolerant rats. However, i.t. BAM8-22 did not completely reverse or inhibit morphine tolerance in formalin test. Moreover, antinociception of morphine were significantly weakened after repeated daily treatments with BAM8-22. These results suggested that SNSR may be able to modulate the sensitivity of opioid receptor in persistent pain. This study also demonstrated that using BAM8-22 to attenuate or reverse morphine tolerance may be a better regimen for long-term use of opioids to treat persistent pain.