The present retrospective study, conducted across two centers, sought to probe into the occurrence of NeP in patients afflicted with traumatic SCI and its potential association with the time from injury to surgery. Several factors, including age at injury, Injury Severity Score, and the neurological level of injury, exhibited links to the development of NeP in both complete and incomplete injury subgroups. Interestingly, in the incomplete SCI subgroups (AIS B, C, and D), delayed surgical intervention was identified as a key contributor to an augmented risk of NeP. These findings furnish compelling evidence reinforcing the advantages of early surgical intervention, notably ultra-early surgery, in mitigating the incidence of NeP after traumatic SCI.
The reported incidence rate of NeP following traumatic SCI displays a wide range of 25–84% [8, 10, 28, 29]. Such variation is primarily attributed to diverse research methodologies, substantial heterogeneity in population characteristics, and the adoption of different definitions and diagnostic criteria for NeP. The present study identified that 48.4% (155 of 320) of patients with traumatic SCI suffered from NeP using the DN4 Neuropathological Pain Scale, which has been reported as a clinical and validated diagnostic tool used for screening acute and chronic neuropathic pain [24, 25, 30].
Moreover, within the subset of patients experiencing NeP, a significant 60.0% were found to exhibit at-level NeP. Notably, and regarding the timeline of NeP occurrence, a substantial proportion (32.9%) of individuals developed NeP within 3 months post-injury, while the majority (67.1%) presented with possible neuropathic pain at the chronic stage (> 3 months). These findings underscore the critical importance of comprehending the temporal evolution of NeP in SCI patients, a factor that can significantly inform clinical management and intervention strategies. Furthermore, our analysis identified several factors consistently associated with the development of NeP in both AIS A and AIS B, C, and D subgroups. Specifically, older age at injury, higher Injury Severity Score (ISS), and more severe neurological injury were all found to be significantly linked to an elevated likelihood of NeP. These associations shed light on the substantial influence of injury severity and patient characteristics on the development of NeP.
The principal focus of this study was to explore the potential impact of the time from injury to surgery on the occurrence of NeP in patients with SCI. Intriguingly, we observed that patients afflicted with NeP exhibited a significantly prolonged duration between injury and surgical intervention compared to those without NeP. This observation suggests a plausible association between delayed surgical intervention and the development of NeP. Earlier research has also reported a correlation between surgical timing and improved clinical outcomes in SCI patients [22, 31, 32]. For instance, Middendorp et al. [22] conducted a systematic review and meta-analysis encompassing studies evaluating the impact of the timing of spinal surgery after traumatic SCI. Their findings highlighted that early spinal surgery was significantly linked to higher total motor and neurological improvement in comparison with late surgery. The influence of early surgery or the timing of surgery on postoperative neuropathic pain in patients with traumatic SCI remains unexplored, representing a critical knowledge gap in the field. In this current investigation, a multivariate logistic regression analysis has revealed a significant association between the time from injury to surgery and NeP in AIS B, C, and D patients, while we failed to demonstrate that the time from injury to surgery affects the occurrence of NeP after injury in AIS A (complete injury) patients. Middendorp et al. corroborated early surgery was significantly linked to higher total motor improvement in comparison with late surgery in the overall population with SCI, while they did not differentiate patients with complete injury from those with incomplete injury. As a previous study reported that the severity of the injury is an important determinant of a patient’s neurological recovery and prognosis, the spontaneous recovery of motor function in patients with AIS A grade (complete injury) is fairly limited, while AIS B patients show greater spontaneous recovery than AIS A patients [33,34,35]. Fawcett et al. [33] reported that over 80% of AIS A patients still maintain AIS A status until 12 months after SCI, with AIS B patients having a spontaneous recovery rate of less than 40%, while AIS C and AIS D patients have more than 60% and 95% improvement, respectively. Therefore, we assumed that AIS A (complete injury) patients have a higher risk of NeP compared to AIS B, C, and D patients, even after early surgery, but this requires further research. In addition, our present study has not reported long-term or ultimate neuropathic pain outcomes, our goal is to study NeP that occurs between 12 months after injury and analyze the impact of early surgical intervention on NeP occurrence. We believe that further follow-up is unlikely to change these conclusions, and it may be necessary to collect complete NeP evaluations at longer time points such as 2 or 5 years in future. Precisely, patients falling under AIS B, C, and D categories who underwent ultra-early surgery within 8 h of injury displayed markedly lower instances of NeP compared to those subjected to late surgery after 24 h (OR 0.148, 95% CI 0.029–0.751). Similarly, patients who underwent early surgery within 24 h of injury also experienced notably reduced NeP compared to those with delayed surgical intervention (OR 0.375, 95% CI 0.148, 0.950). These findings underscore the potential benefit of early surgical intervention in mitigating the risk of NeP, particularly among specific AIS subgroups. However, the exact mechanisms underlying this observed reduction in neuropathic pain following early/timely surgery necessitate further exploration. Post-traumatic SCI, the presence of tissue bleeding, edema, and adhesion triggers an elevation in pressure within the spinal canal, consequently setting in motion pathological and physiological processes involving ischemia and hypoxia. This, in turn, escalates the cascading reaction of secondary spinal cord injury [2, 3]. Employing an early/timely surgical approach alongside an appropriate decompression strategy can effectively curtail secondary injury [20, 32, 36]. Secondary injury including microglia activation and subsequent release of proinflammatory cytokines like TNF-α, IL-6, and IL-1β [37, 38], as well as ion channel accumulation and abnormal neurotransmitter expression [39, 40], all play crucial roles in the activation of NeP. By intervening early, it becomes plausible to avert the activation of pain pathways and the subsequent sensitization of neural circuits implicated in pain perception [41].
Additionally, our study has shed light on a compelling association, wherein patients experiencing Neuropathic Pain (NeP) were notably more prone to receiving high-dose methylprednisolone therapy during the acute phase. It is important to note that the employment of high-dose methylprednisolone is presently discouraged due to its significant systemic adverse effects [41]. Nevertheless, this intriguing finding calls for an in-depth investigation to ascertain whether the administration of methylprednisolone influences the development of NeP or merely reflects the outcome of more severe injuries.
This study represents the attempt at a comprehensive exploration of the factors underlying NeP in patients with traumatic SCI. The findings unveiled that delayed or late surgery may emerge as a noteworthy risk factor contributing to the presence of NeP. However, it is imperative to acknowledge the inherent limitations inherent in this study. Primarily, its retrospective nature introduces biases and constraints in data collection. To corroborate these findings, prospective studies with larger sample sizes and standardized protocols are indispensable. Secondarily, in the present study cohort, neuropathic pain was screened using the DN4 questionnaire as it was an ideal and validated tool for screening neuropathic pain [25, 42], the diagnosis of neuropathic pain should essentially be based on the descriptors used by the patients and the clinical physical examination results [42], validated tools and investigations should not replace detailed clinical evaluations, which may affect the robustness of our results. Thirdly, this study omitted the specific intraoperative intricacies, such as the surgical approach, decompression techniques, and the performance of stabilization procedures. Moreover, the impact and timing of preoperative closed reduction remain unreported. Notwithstanding the surgeries conducted by dedicated surgical teams at both centers, this aspect might still potentially attenuate the robustness of our conclusions. Additionally, a thorough confirmation of the extent of preoperative spinal cord compression and the efficacy of surgical interventions in fully alleviating compression or ensuring effective spinal stabilization were not specifically ascertained. Thirdly, the study lacked objective indicators for evaluating neuropathic pain, including sophisticated neurophysiological techniques like nerve conduction studies, the measurement of somatosensory-evoked potentials (SEPs), and trigeminal reflexes. These techniques play a pivotal role in confirming, localizing, and quantifying central and peripheral sensory conduction damage. Hence, future investigations should incorporate uniform pain assessment tools to ensure methodological consistency and bolster reliability.
Add Comment