Context: Central neuropathic pain (CNP) affects about half of individuals post-spinal cord injury (SCI) and is often resistant to treatment. The risk for CNP is linked to enhanced pain excitability and reduced pain inhibition; early intervention targeting these pathological processes may mitigate the risk. Pregabalin, a first-line agent for (chronic) neuropathic pain, reduces hyperexcitability, yet its potential to prevent CNP is unknown. We evaluated the efficacy of preemptive pregabalin in reducing CNP's incidence and severity post-SCI.Methods: In this prospective controlled observational study 30 individuals with SCI participated; 11 received preemptive pregabalin (150 mg/day for 12 weeks), and 19 served as untreated controls. Assessments occurred at baseline (T1), 6 weeks (T2), and 12 weeks (T3), and at 6-month post-intervention (T4, follow-up).Outcomes included: CNP incidence, pain intensity (McGill Pain Questionnaire), body area involvement, allodynia, and baseline pain modulation (offset analgesia, pain adaptation).Results: At T2 and T3, CNP incidence was significantly lower in the pregabalin group (0% and 9.1%, respectively) than controls (31.6% and 52.6%, respectively, p < 0.05), with a sustained trend at T4. Moreover, compared to controls, CNP onset in the pregabalin group was delayed, and pain intensity, body area involvement, and allodynia were reduced. Impaired baseline pain modulation predicted CNP development in both groups. Treatment was well tolerated with minimum adverse effects.Conclusions: Early, low-dose pregabalin may delay and/or prevent CNP post-SCI and reduce its severity, with fewer side effects than chronic dosing. Screening for impaired pain modulation may identify high-risk individuals who could benefit from preventive treatment.
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