Department of Physical Therapy at Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Department of Neurological Rehabilitation, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
Pain. 2022 Jan 1;163(1):e94-e105. doi: 10.1097/j.pain.0000000000002315.
A severe and debilitating consequence of a spinal cord injury (SCI) is central neuropathic pain (CNP). Our aim was to investigate the processes leading to CNP emergence and chronification by analyzing causal relationship over time between spinothalamic function, pain excitability, and pain inhibition after SCI. This longitudinal follow-up study included 53 patients with acute SCI and 20 healthy controls. Spinothalamic, pain excitability, and intrasegmental and extrasegmental pain inhibition indices were repeatedly evaluated at 1.5, 3, and 6 months post-SCI. Between- and within-group analyses were conducted among those patients who eventually developed CNP and those who did not. Healthy controls were evaluated twice for repeatability analysis. Patients who developed CNP, compared with those who did not, exhibited increased thermal thresholds (P < 0.05), reduced pain adaptation (P < 0.01), and conditioned pain modulation (P < 0.05), early post-injury, and the CNP group's manifestations remained worse throughout the follow-up. By contrast, allodynia frequency was initially similar across SCI groups, but gradually increased in the subacute phase onward only among the CNP group (P < 0.001), along with CNP emergence. Early worse spinothalamic and pain inhibition preceded CNP and predicted its occurrence, and early worse pain inhibition mediated the link between spinothalamic function and CNP. Crossover associations were observed between early and late pain inhibition and excitability. Inefficient intrasegmental and extrasegmental inhibition, possibly resulting from spinothalamic deafferentation, seems to ignite CNP chronification. Pain excitability probably contributes to CNP maintenance, possibly via further exhaustion of the inhibitory control. Preemptive treatment promoting antinociception early post-SCI may mitigate or prevent CNP.
脊髓损伤 (SCI) 的一个严重和使人虚弱的后果是中枢神经性疼痛 (CNP)。我们的目的是通过分析 SCI 后痛觉传入、痛觉兴奋性和痛觉抑制的因果关系随时间的变化，来研究导致 CNP 出现和慢性化的过程。这项纵向随访研究包括 53 例急性 SCI 患者和 20 名健康对照者。在 SCI 后 1.5、3 和 6 个月时，反复评估痛觉传入、痛觉兴奋性、节段内和节段外痛觉抑制指数。对最终出现 CNP 和未出现 CNP 的患者进行组间和组内分析。健康对照者进行了两次评估，以进行可重复性分析。与未发生 CNP 的患者相比，发生 CNP 的患者在受伤后早期表现出热阈值升高（P < 0.05）、痛觉适应降低（P < 0.01）和条件性疼痛调制降低（P < 0.05），并且在整个随访过程中 CNP 组的表现仍然较差。相比之下，所有痛觉过敏的频率在 SCI 组之间早期相似，但仅在 CNP 组中，在亚急性期后逐渐增加（P < 0.001），并伴随着 CNP 的出现。早期较差的痛觉传入和抑制先于 CNP 发生，并预测其发生，早期较差的抑制介导了痛觉传入和 CNP 之间的联系。早期和晚期抑制与兴奋性之间存在交叉关联。可能由于痛觉传入的去传入，节段内和节段外抑制效率降低，似乎引发了 CNP 的慢性化。痛觉兴奋性可能有助于 CNP 的维持，可能是通过进一步耗尽抑制控制。早期 SCI 后促进镇痛的预防性治疗可能减轻或预防 CNP。
