Mitchell J M, Lowe D, Fields H L
Department of Neurology, W. M. Keck Center for Integrative Neuroscience, UCSF, San Fransisco, CA 941143, USA.
Neuroscience. 1998 Nov;87(1):123-33. doi: 10.1016/s0306-4522(98)00119-5.
Although there are numerous opioid-sensitive structures in the central nervous system, the contribution of each to the analgesic effect of systemically administered morphine is controversial. One such structure is the rostral ventromedial medulla. In the present study, we tested the hypothesis that the rostral ventromedial medulla is necessary for the full expression of systemic morphine-induced antinociception. Additionally, we examined whether the modulatory effect of the rostral ventromedial medulla on tail-flick latency is dependent on the behavioral state of the animal. In unrestrained rats, inactivation of the rostral ventromedial medulla with either lidocaine (0.5 microl of 4%) or muscimol (50 ng) had no effect on tail-flick latency. In contrast, in restrained rats, inactivation of the rostral ventromedial medulla with either lidocaine (0.5 microl of 4%) or muscimol (50 ng) significantly decreased tail-flick latency. In both conditions, microinjection of morphine (5 microg) into this region significantly increased tail-flick latency. Additionally, in unrestrained rats, muscimol (50 ng) and cholecystokinin tetrapeptide (0.5 ng) infusion into the rostral ventromedial medulla completely reversed systemic morphine-induced analgesia, while lidocaine (0.5 microl of 4%) and cholecystokinin octapeptide (0.25 ng) infusion partially reversed systemic morphine-induced analgesia. These findings demonstrate that the rostral ventromedial medulla does not tonically modulate tail-flick latency in unrestrained rats, but does modulate tail-flick latency when animals are stressed via restraint. These findings also strongly support the hypothesis that the rostral ventromedial medulla is necessary for the full analgesic effects of systemically administered morphine.
虽然中枢神经系统中有众多对阿片类药物敏感的结构，但它们各自对全身给药吗啡镇痛作用的贡献存在争议。延髓头端腹内侧核就是这样一种结构。在本研究中，我们检验了这样一个假说，即延髓头端腹内侧核对于全身吗啡诱导的镇痛作用的充分表达是必需的。此外，我们还研究了延髓头端腹内侧核对甩尾潜伏期的调节作用是否依赖于动物的行为状态。在未束缚的大鼠中，用利多卡因（4%的0.5微升）或蝇蕈醇（50纳克）使延髓头端腹内侧核失活对甩尾潜伏期没有影响。相反，在束缚的大鼠中，用利多卡因（4%的0.5微升）或蝇蕈醇（50纳克）使延髓头端腹内侧核失活显著缩短了甩尾潜伏期。在这两种情况下，向该区域微量注射吗啡（5微克）均显著延长了甩尾潜伏期。此外，在未束缚的大鼠中，向延髓头端腹内侧核注入蝇蕈醇（50纳克）和胆囊收缩素四肽（0.5纳克）完全逆转了全身吗啡诱导的镇痛作用，而注入利多卡因（4%的0.5微升）和胆囊收缩素八肽（0.25纳克）则部分逆转了全身吗啡诱导的镇痛作用。这些发现表明，延髓头端腹内侧核在未束缚的大鼠中不会持续调节甩尾潜伏期，但在动物因束缚而受到应激时会调节甩尾潜伏期。这些发现也有力地支持了这样一个假说，即延髓头端腹内侧核对于全身给药吗啡的充分镇痛作用是必需的。
