Abstract
Background/Objectives: Although increased nociceptive excitability and deficient endogenous pain modulation are considered key features of pronociception and central sensitization, their contribution to neuropathic pain (NP) characteristics in SCI is unclear. The aim of this study was to characterize tonic cold perception and endogenous pain modulation in individuals with and without SCI-NP, considering the stage and severity of SCI and, secondarily, NP phenotype. Methods: Temporal summation of pain (TSP) and neuropathic features were assessed using the numerical rating scale (NRS) and Douleur Neuropathique 4 screening questionnaire (DN4) during the tonic cold pressor test (CPT, 12 °C 60 s) applied to the dominant hand and foot. CPT-induced pronociception was assessed as change in algometer pressure pain thresholds (PPTs) measured at the V2, C6, and L4 dermatomes. Results: A total of 72 individuals were recruited (age-sex-matched noninjured, n = 24; SCI-NP, n = 24; SCI-noNP, n = 24 [AIS A: n = 12, AIS B-D: n = 12; subacute SCI: n = 12, chronic SCI: n = 12]). TSP in response to the foot CPT was higher in subacute compared to chronic incomplete SCI-NP, while TSP to the hand CPT was significantly higher in chronic compared to the subacute complete SCI-NP group. Evoked pain intensity during the hand CPT correlated with duration of below-level SCI-NP. The hand CPT induced widespread pronociception (lower PPT), which correlated with 7-day non-evoked (spontaneous) pain intensity in individuals with incomplete SCI-NP. Individuals with below-level NP, but not at-level NP, showed higher TSP during the foot CPT and greater hand CPT-induced L4 dermatome pronociception. Conclusions: Collectively, measurements of above and below-level temporal summation of pain and translesional-induced pronociception in the SCI-NP group highlight the role of these mechanisms in widespread central sensitization, spontaneous pain intensity, and spinothalamic tract hyperexcitability, especially in individuals diagnosed with below-level NP.