Identifying Discomplete Spinal Lesions: New Evidence from Pain-Autonomic Interaction in Spinal Cord Injury

Abstract

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions, i.e., residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared to objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively).Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%) and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relation was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%).In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discern STT lesion completeness might support revealing the interference with neuropathic pain following SCI.

Pre-Injury Mechanoreceptor Ablation Reduces Nociceptor-Driven Spinal Cord Injury-Induced Neuropathic Pain

“…Standardized sensory examination according to International Standards for Neurological Classification of SCI (ISNCSCI) in subacute traumatic and ischemic SCI patients observed within the European Multicenter Study about Spinal Cord Injury (EMSCI) revealed relative preservation of the spinothalamic tract (pinprick sensation), which predisposes for NP presentation (unpublished observation). In clinically sensorimotor complete SCI subjects (AIS-A), an instrumented analysis with contact-heat evoked measurements (CHEPS) also identified partial preservation of the spinothalamic tract to be associated with NP (35).…”

“…Unfortunately, the poor health condition of SNS iDTR mice in our hands with the presentation of seizures was not sufficient to inflict contusion SCI and a prolonged survival period on these animals. In SNS tdTomato we observed a leaky reporter expression that based on breeding records could be traced back to Rosa26LSL-tdTomato mice -A), an instrumented analysis with contact-heat evoked measurements (CHEPS) also identified partial preservation of the spinothalamic tract to be associated with NP (35).…”

“…In subjects suffering from subacute traumatic SCI, hypersensitivity to mechanical pain stimuli -A), an instrumented analysis with contact-heat evoked measurements (CHEPS) also identified partial preservation of the spinothalamic tract to be associated with NP (35).…”

Pain‐autonomic interaction is a reliable measure of pain habituation in healthy subjects

“…This might be an explanation for the observed differences in habituation for the three different readouts. In this regard, a recent study from our group (Lütolf et al, 2021) also reported diverging results when investigating the integrity of ascending nociceptive projections in subjects with spinal cord injury employing the same three readouts. There a potential contribution of different neural structures in the generation of pain ratings, CHEPs and SSRs were discussed to explain the diverging results.…”

Sympathetic skin response as an objective tool to estimate stimulus-associated arousal in a human model of hyperalgesia

“…In contrast with other autonomic signals, the SSR is thought to be largely independent of adrenergic agents, haemodynamic variability and respiratory rate [41]. While SSR has shown its ability to respond to noxious stimuli such as laser or thermode pulses [6,26,28] and to detect hypalgesia due to neural lesions such as syringomyelia [48], its ability to detect abnormal subjective perception, including pain, in states of pathological or experimental hypersensitivity consistent with routine clinical practice has scarcely been explored [31,39].…”