Catherine R. Jutzeler

Association of pain and CNS structural changes after spinal cord injury

Traumatic spinal cord injury (SCI) has been shown to trigger structural atrophic changes within the spinal cord and brain. However, the relationship between structural changes and magnitude of neuropathic pain (NP) remains incompletely understood. Voxel-wise analysis of anatomical magnetic resonance imaging data provided information on cross-sectional cervical cord area and volumetric brain changes in 30 individuals with chronic traumatic SCI and 31 healthy controls. Participants were clinically assessed including neurological examination and pain questionnaire. Compared to controls, individuals with SCI exhibited decreased cord area, reduced grey matter (GM) volumes in anterior cingulate cortex (ACC), left insula, left secondary somatosensory cortex, bilateral thalamus, and decreased white matter volumes in pyramids and left internal capsule. The presence of NP was related with smaller cord area, increased GM in left ACC and right M1, and decreased GM in right primary somatosensory cortex and thalamus. Greater GM volume in M1 was associated with amount of NP. Below-level NP-associated structural changes in the spinal cord and brain can be discerned from trauma-induced consequences of SCI. The directionality of these relationships reveals specific changes across the neuroaxis (i.e., atrophic changes versus increases in volume) and may provide substrates of underlying neural mechanisms in the development of NP.

Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings

Background Mechanisms underlying the development of phantom limb pain and neuropathic pain after limb amputation and spinal cord injury, respectively, are poorly understood. The goal of this systematic review was to assess the robustness of evidence in support of “maladaptive plasticity” emerging from applications of advanced functional magnetic resonance imaging (MRI). Methods Using MeSH heading search terms in PubMed and SCOPUS, a systematic review was performed querying published manuscripts. Results From 146 candidate publications, 10 were identified as meeting the inclusion criteria. Results from fMRI investigations provided some level of support for maladaptive cortical plasticity, including longitudinal studies that demonstrated a change in functional organization related to decreases in pain. However, a number of studies have reported no relationship between reorganization, pain and deafferentation, and emerging evidence has also suggested the opposite — that is, chronic pain is associated with preserved cortical function. Conclusion Based solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

Improving the acquisition of nociceptive evoked potentials without causing more pain

Summary Causing a greater subjective pain experience is not necessary for improving the objective assessment of pain using contact heat‐evoked potentials. ABSTRACT Following nociceptive heat or laser stimulation, an early contralateral and later vertex potential can be recorded. Although more indicative of the nociceptive input, the acquisition of the contralateral N1 after contact heat stimulation (contact heat‐evoked potentials [CHEPs]) remains difficult. An advantage of contact heat is that the baseline skin temperature preceding peak stimulation can be controlled. Increasing the baseline temperature may represent a novel strategy to improve the acquisition of CHEPs without resulting in more subjective pain to stimulation. A study was undertaken in 23 healthy subjects to examine the effects of increasing the baseline temperature but not the perceived intensity of contact heat stimulation. A combined standard averaging and single‐trial analysis was performed to disclose how changes in averaged waveforms related to latency jitter and individual trial amplitudes. By increasing the baseline temperature, the acquisition of N1 was improved among subjects with a low‐amplitude response (greater than −4 μV) following 35°C baseline temperature stimulation (P < .05). Based on standard averaging, N2/P2 amplitudes were also significantly increased with and without an accompanying change in the rating of perceived pain when the baseline temperature was increased (P < .05). In contrast, automated single‐trial averaging revealed no significant difference in N2 amplitude when the baseline temperature was increased to 42°C and the peak temperature reduced. These findings suggest that 2 mechanisms underlie the improved acquisition of CHEPs: increased synchronization of afferent volley, yielding larger‐amplitude evoked potentials in response to the same rating of intensity; and reduced inter‐trial variability.

Spinal cord injury affects the interplay between visual and sensorimotor representations of the body

The brain integrates multiple sensory inputs, including somatosensory and visual inputs, to produce a representation of the body. Spinal cord injury (SCI) interrupts the communication between brain and body and the effects of this deafferentation on body representation are poorly understood. We investigated whether the relative weight of somatosensory and visual frames of reference for body representation is altered in individuals with incomplete or complete SCI (affecting lower limbs’ somatosensation), with respect to controls. To study the influence of afferent somatosensory information on body representation, participants verbally judged the laterality of rotated images of feet, hands, and whole-bodies (mental rotation task) in two different postures (participants’ body parts were hidden from view). We found that (i) complete SCI disrupts the influence of postural changes on the representation of the deafferented body parts (feet, but not hands) and (ii) regardless of posture, whole-body representation progressively deteriorates proportionally to SCI completeness. These results demonstrate that the cortical representation of the body is dynamic, responsive, and adaptable to contingent conditions, in that the role of somatosensation is altered and partially compensated with a change in the relative weight of somatosensory versus visual bodily representations.

Neuropathic Pain and Functional Reorganization in the Primary Sensorimotor Cortex After Spinal Cord Injury.

UNLABELLED Refractory to most types of treatment, neuropathic pain (NP) is a major problem for people living with spinal cord injury (SCI). The underlying mechanisms among problems related to treatment are poorly understood. The aim of the present study was to investigate the association between cortical reorganization and NP after SCI. Twenty-four individuals with sensorimotor complete and incomplete paraplegia and tetraplegia (12 with NP, 13 pain free) and 31 healthy individuals were examined. Functional magnetic resonance imaging was used to assess activation in primary somatosensory and motor cortices in response to motor (ie, active and passive wrist extension) and sensory (ie, heat and brushing) tasks applied on the dorsum of the hand. In individuals with SCI, there were no group-level differences in task-related activation (ie, movement or sensory) compared with the healthy controls. However, based on the Euclidean distance measure, individuals with SCI demonstrated a lateral shift of peak activity in primary sensory and motor cortices (P < .05). Among those with NP, chronic pain intensity inversely correlated with the magnitude of the shift in the primary motor cortex during active wrist extension. The findings reveal that NP in motor and sensory tasks at or above the level of the lesion is not associated with increased plasticity. In line with previous studies, changes in somatotopy and activation after SCI are rather limited and the influence of NP on plasticity remains controversial. PERSPECTIVE Using functional magnetic resonance imaging, we have provided novel evidence that reorganization (i.e., topographical shifts in peak activity) in the primary motor cortex after spinal cord injury is limited to individuals without neuropathic pain.

Effects of Pain and Pain Management on Motor Recovery of Spinal Cord–Injured Patients: A Longitudinal Study

Background. Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. Objective. The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. Methods. We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. Results. A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. Conclusion. While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI.

An Objective Measure of Stimulus-Evoked Pain

For most clinical assessments, reporting perception of a painful event has relied on subjective ratings [e.g., the visual analog scale (VAS)]. A more quantifiable and objective method is desirable, preferably one that is directly related to the physiological processing of nociceptive stimuli. An

Normative data for the segmental acquisition of contact heat evoked potentials in cervical dermatomes

Contact heat evoked potentials (CHEPs) represent a neurophysiological approach to assess conduction in the spinothalamic tract. The aim of this study was to establish normative values of CHEPs acquired from cervical dermatomes (C4, C6, C8) and examine the potential confounds of age, sex, and height. 101 (49 male) healthy subjects of three different age groups (18–40, 41–60, and 61–80 years) were recruited. Normal (NB, 35–52 °C) followed by increased (IB, 42–52 °C) baseline stimulation protocols were employed to record CHEPs. Multi-variate linear models were used to investigate the effect of age, sex, and height on the CHEPs parameters (i.e., N2 latency, N2P2 amplitude, rating of perceived intensity). Compared to NB, IB stimulation reduced latency jitter within subjects, yielding larger N2P2 amplitudes, and decreased inter-subject N2 latency variability. Age was associated with reduced N2P2 amplitude and prolonged N2 latency. After controlling for height, male subjects had significantly longer N2 latencies than females during IB stimulation. The study provides normative CHEPs data in a large cohort of healthy subjects from segmentally examined cervical dermatomes. Age and sex were identified as important factors contributing to N2 latency and N2P2 amplitude. The normative data will improve the diagnosis of spinal cord pathologies.

Effectiveness of High-Frequency Electrical Stimulation Following Sensitization With Capsaicin

UNLABELLED Although nonnoxious, high-frequency electrical stimulation applied segmentally (ie, conventional transcutaneous electrical nerve stimulation [TENS]) has been proposed to modulate pain, the mechanisms underlying analgesia remain poorly understood. To further elucidate how TENS modulates pain, we examined evoked responses to noxious thermal stimuli after the induction of sensitization using capsaicin in healthy volunteers. We hypothesized that sensitization caused by capsaicin application would unmask TENS analgesia, which could not be detected in the absence of sensitization. Forty-nine healthy subjects took part in a series of experiments. The experiments comprised the application of topical capsaicin (.075%) on the left hand in the C6 dermatome, varying the location of TENS (segmental, left C6 dermatome, vs extrasegmental, right shoulder), and assessing rating of perception (numeric rating scale: 0-10) and evoked potentials to noxious contact heat stimuli. The extrasegmental site was included as a control condition because previous studies indicate no analgesic effect to remote conventional TENS. Conventional TENS had no significant effect on rating or sensory evoked potentials in subjects untreated with capsaicin. However, segmental TENS applied in conjunction with capsaicin significantly reduced sensation to noxious thermal stimuli following a 60-minute period of sensitization. PERSPECTIVE The study indicates that sensitization with capsaicin unmasks the analgesic effect of conventional TENS on perception of noxious contact heat stimuli. Our findings indicate that TENS may be interacting segmentally to modulate distinct aspects of sensitization, which in turn results in analgesia to thermal stimulation.

Discrepancy between perceived pain and cortical processing: A voxel-based morphometry and contact heat evoked potential study

OBJECTIVES The purpose of this study was to determine if local gray and white matter volume variations between subjects could account for variability in responses to CHEP stimulation. METHODS Structural magnetic resonance imaging was used to perform voxel-based morphometry (VBM) of gray and white matter in 30 neurologically healthy subjects. Contact heat stimulation was performed on the dorsum of the right hand at the base of the thumb. Evoked potentials were acquired from a vertex-recording electrode referenced to linked ears. RESULTS Controlling for age, total intracranial volume, and skull/scalp thickness, CHEP amplitude and pain rating were not significantly correlated between subjects. A VBM region of interest approach demonstrated a significant interaction between pain rating and N2 amplitude in the right insular cortex (p<0.05, family-wise error corrected, FWE). In white matter, a significant interaction was localized in the right inferior frontal occipital fasciculus (IFOF, p<0.05 FWE). CONCLUSIONS Accounting for gray matter volume in the right insular cortex, resulted in a significant relationship between CHEP amplitude and pain rating. SIGNIFICANCE This finding suggests that the discrepancy between pain ratings and the amplitude of evoked potentials is not solely related to measurement artifact, but rather attributable, in part, to anatomical differences between subjects.