Mechanical and thermal allodynia in chronic central pain following spinal cord injury
Mechanical and thermal allodynia in chronic central pain following spinal cord injury
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DOI：
10.1016/s0304-3959(96)03224-1
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发表时间：
1996-11-01
期刊：
影响因子：
7.4
通讯作者：
Hulsebosch, CE
中科院分区：
文献类型：
--
作者：
Christensen, MD;Everhart, AW;Hulsebosch, CE
脊髓损伤 (SCI) 导致大多数 SCI 患者的运动恢复能力不稳定，并出现慢性中枢性疼痛综合征。为了为进一步研究提供基础，我们报告了一种新的脊髓损伤后慢性中枢性疼痛的啮齿动物模型。将雄性 Sprague-Dawley 大鼠 (N = 10) 在 T13 处进行半剖，并在术前和术后进行测试，并与假手术对照 (N = 10) 进行运动功能、缩爪和脊髓上反应的机械和热阈值的比较。结果支持异常性疼痛的发生和持续，持续 160 天。使用 Basso、Beattie 和 Bresnahan (BBB) 旷场测试测试运动功能，仅半切的同侧肢体受到影响，表明急性弛缓性麻痹，运动恢复到术后第 15 天 (POD) 接近正常值。半切之前，大鼠对前肢和前肢 4.41 mN 或 9.41 mN 的 von Prey 刺激几乎没有或没有爪缩回反应。后肢。术后，同侧和对侧前肢和后肢的反应随着时间的推移而增加，并且与动物内术前和假手术对照值相比，增加具有统计学显着性（P < 0.05）。术前或超过 POD 15 后，肢体反应没有显着的左右差异。术前和术后前肢和后肢对 122 mN von Frey 毛发强度的反应具有相似的退出频率，但不具有统计学意义。术前，后肢和前肢对热刺激的缩爪潜伏期分别为 22.9 +/- 3.0（平均值 +/- SE）和 20.1 +/- 3.1 秒。术后，平均后肢和前肢缩爪潜伏期分别减少至 11.9 +/- 1.8 和 9.2 +/- 2.5 秒。与动物内术前和假手术对照值相比，热阈值的降低具有统计学意义（P < 0.05）。这些数据表明，引起缩爪（屈肌反射）的无害机械和辐射热的体感阈值在 SCI 后显着降低。为了进一步支持半切后慢性疼痛的发展和持续，对机械和热刺激做出反应，引起诸如舔爪、转头、攻击刺激和发声等脊髓上反应，并且与术前动物内或假手术对照值相比具有统计学显着性（P < 0.05）。与动物内术前和假手术对照值为零相比，半切动物在 49.8 的 von Frey 头发弯曲力下发声，10 次刺激中平均为 6.0 +/- 1.2 次。半切动物对热刺激的脊柱上反应发生在较低的温度下，与假手术对照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 SCI 后机械和热异常性疼痛的发展和持续。
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 Prey 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.