From acute to long-term alterations in pain processing and modulation after spinal cord injury: Mechanisms related to chronification of central neuropathic pain

Ruth Defrin, Hila Gruener, Evgeni Gaidukov, Moshe Bondi, Orna Rachamim-Katz, Erez Ringler, Nava Blumen, Gabi Zeilig

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)E94-E105
JournalPain
Volume163
Issue number1
DOIs
StatePublished - 1 Jan 2022

Keywords

  • Central neuropathic pain
  • Chronicity
  • Extrasegmental
  • Hyperexcitability
  • Inhibition
  • Intrasegmental inhibition
  • Longitudinal study
  • Mechanisms

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