Christensen Marc D, Everhart Alex W, Pickelman Jason T, Hulsebosch Claire E
Marine Biomedical Institute and Department of Anatomy and Neurosciences, The University of Texas Medical Branch,Galveston, TX 77555-1069,USA.
Pain. 1996 Nov;68(1):97-107. doi: 10.1016/S0304-3959(96)03224-1.
Spinal cord injury (SCI) results in variable motor recoveries and chronic central pain syndromes develop in the majority of SCI patients. To provide a basis for further studies, we report a new rodent model of chronic central pain following spinal cord trauma. Male Sprague-Dawley rats (N = 10) were hemisectioned at T13 and were tested both preoperatively and postoperatively and compared to sham-operated controls (N = 10) for locomotor function, and mechanical and thermal thresholds of both paw withdrawal and supraspinal responses. Results support the development and persistence of allodynia which persists for 160 days. Locomotor function was tested using the Basso, Beattie and Bresnahan (BBB) open field test and only the limb ipsilateral to the hemisection was affected, demonstrating acute flaccid paralysis with motor recovery which approached normal values by postoperative day (POD) 15. Prior to the hemisection, the rats showed little to no paw withdrawal response to von Frey stimulation of 4.41 mN or 9.41 mN in both forelimbs and hindlimbs. Postoperatively, responses in both ipsilateral and contralateral forelimbs and hindlimbs increased over time and the increase was statistically significant compared to intra-animal presurgical and sham control values (P < 0.05). There were no significant side-to-side differences in limb responses preoperatively or beyond POD 15. The forelimbs and hindlimbs responded to von Frey hair strengths of 122 mN preoperatively and postoperatively with similar withdrawal frequencies that were not statistically significant. Preoperatively, the paw withdrawal latency to heat stimuli was 22.9 +/- 3.0 (mean +/- SE) and 20.1 +/- 3.1 sec for the hindlimbs and forelimbs, respectively. Postoperatively, the mean hindlimb and forelimb latency of paw withdrawals decreased to 11.9 +/- 1.8 and 9.2 +/- 2.5 sec, respectively. This decrease in thermal thresholds is statistically significant when compared to intra-animal preoperative and sham control values (P < 0.05). These data indicate that somatosensory thresholds for non-noxious mechanical and radiant heat which elicit paw withdrawal (flexor reflex) are significantly lowered following SCI. To further support the development and persistence of chronic pain following hemisection, supraspinal responses such as paw lick, head turns, attacking the stimulus, and vocalizations were elicited in response to mechanical and thermal stimuli and were statistically significant compared to presurgical intra-animal or sham control values (P < 0.05). Hemisected animals vocalized to von Frey hair bending forces of 49.8 with a mean of 6.0 +/- 1.2 times out of 10 stimuli compared to intra-animal presurgical and sham control values of zero. Supraspinal responses of hemisected animals to thermal stimuli occurred at lower temperatures that were statistically significant compared to sham control or preoperative values (P < 0.05). These chronic changes in thresholds to both mechanical and thermal stimuli represent the development and persistence of mechanical and thermal allodynia after SCI.
脊髓损伤(SCI)会导致不同程度的运动恢复,并且大多数SCI患者会出现慢性中枢性疼痛综合征。为了为进一步研究提供依据,我们报告一种新的脊髓损伤后慢性中枢性疼痛的啮齿动物模型。将10只雄性Sprague-Dawley大鼠在T13水平进行半横断,并在术前和术后进行测试,同时与假手术对照组(10只)比较运动功能以及双爪退缩和脊髓上反应的机械和热阈值。结果支持痛觉过敏的发生和持续存在,这种情况持续了160天。使用Basso、Beattie和Bresnahan(BBB)旷场试验测试运动功能,只有半横断同侧的肢体受到影响,表现为急性弛缓性麻痹并伴有运动恢复,到术后第15天接近正常值。在半横断之前,大鼠对前肢和后肢4.41 mN或9.41 mN的von Frey刺激几乎没有或没有爪退缩反应。术后,同侧和对侧前肢及后肢的反应随时间增加,与动物术前和假手术对照组值相比,这种增加具有统计学意义(P < 0.05)。术前或术后第15天之后,肢体反应在左右侧之间没有显著差异。前肢和后肢术前和术后对122 mN的von Frey毛发强度的反应具有相似的退缩频率,无统计学意义。术前,后肢和前肢对热刺激的爪退缩潜伏期分别为22.9 +/- 3.0(平均值 +/- 标准误)和20.1 +/- 3.1秒。术后,后肢和前肢爪退缩的平均潜伏期分别降至11.9 +/- 1.8和9.2 +/- 2.5秒。与动物术前和假手术对照组值相比,这种热阈值的降低具有统计学意义(P < 0.05)。这些数据表明,SCI后引发爪退缩(屈肌反射)的非伤害性机械和辐射热的体感阈值显著降低。为了进一步支持半横断后慢性疼痛的发生和持续存在,对机械和热刺激引发了脊髓上反应,如舔爪、转头、攻击刺激和发声,与术前动物内或假手术对照组值相比具有统计学意义(P < 0.05)。与动物术前和假手术对照组值为零相比,半横断动物对49.8的von Frey毛发弯曲力发声,平均每10次刺激中有6.0 +/- 1.2次。半横断动物对热刺激的脊髓上反应发生在较低温度下,与假手术对照组或术前值相比具有统计学意义(P < 0.05)。机械和热刺激阈值的这些慢性变化代表了SCI后机械性和热性痛觉过敏的发生和持续存在。