Crosby Steven J, Knapp Clifford M, Kornetsky Conan
Department of Psychiatry, Boston University School of Medicine, 715 Albany Street, R-620, Boston, MA 02118, USA.
Pharmacol Biochem Behav. 2006 May;84(1):148-57. doi: 10.1016/j.pbb.2006.04.021. Epub 2006 Jun 8.
The present experiment compared the nociceptive threshold and analgesic response to morphine in young (4-5 months) and aged (24 months) rats using peripheral thermal stimulation and intracerebral electrical stimulation. Responses to thermal stimuli were assessed using both the classical tail-flick procedure in which latency of response is the dependent variable and a new method in which threshold in calories of heat is the dependent variable. In the intracerebral nociceptive threshold procedure, electrical stimuli were delivered via an electrode implanted in the mesencephalic reticular formation (MRF), a pain pathway, and the animals were trained to terminate the stimulation by turning a cylindrical manipulandum embedded in one wall of the experimental chamber. For the classical tail-flick method, the aged rats required a greater intensity of stimulation to produce a basal response latency that was between 2.5 and 3.5 s. Using the new psychophysical method for determining the tail-flick threshold, the aged rats' basal thresholds were significantly higher than that of the young rats. However, the basal thresholds obtained by direct stimulation of the MRF failed to show a significant age effect, suggesting that the registration of pain is not different between young and aged rats. These age-related differences in baseline tail-flick response may be due to changes in the spinal reflex associated with aging. Although, there was no difference in the analgesic effects of morphine between young and aged rats using the latency of the tail-flick response, evidence for decreased analgesic response was seen using the tail-flick threshold measure and the intracerebral stimulation threshold method.
本实验采用外周热刺激和脑内电刺激,比较了年轻(4 - 5个月)和老年(24个月)大鼠对伤害性刺激的阈值以及对吗啡的镇痛反应。使用经典的甩尾程序(其中反应潜伏期为因变量)和一种新方法(其中热卡阈值为因变量)来评估对热刺激的反应。在脑内伤害性刺激阈值程序中,通过植入中脑网状结构(MRF,一条疼痛通路)的电极施加电刺激,训练动物通过转动嵌入实验箱一侧壁的圆柱形操作柄来终止刺激。对于经典的甩尾方法,老年大鼠需要更强的刺激强度才能产生2.5至3.5秒之间的基础反应潜伏期。使用新的心理物理学方法测定甩尾阈值时,老年大鼠的基础阈值显著高于年轻大鼠。然而,直接刺激MRF获得的基础阈值未显示出显著的年龄效应,这表明年轻和老年大鼠对疼痛的感受并无差异。这些与年龄相关的基线甩尾反应差异可能是由于与衰老相关的脊髓反射变化所致。尽管使用甩尾反应潜伏期时,年轻和老年大鼠对吗啡的镇痛效果没有差异,但使用甩尾阈值测量和脑内刺激阈值方法时,可观察到镇痛反应降低的证据。