Eva Widerstrom-Noga, Ph.D.

Interdisciplinary Neuropathic Pain Research Program

Background: Many people with spinal cord injury (SCI) or traumatic brain injury (TBI) develop chronic pain, including pain that is neuropathic in nature. Pharmacological treatments for neuropathic pain are often inadequate by themselves because this pain type depends on many different underlying mechanisms and contributing factors. Therefore, multimodal treatment strategies including pain education, pharmacological, physical, and cognitive approaches may be best suited to manage neuropathic pain in this population.

One approach used to uncover underlying mechanisms include phenotyping using pain symptoms and somatosensory function. However, this approach does not consider cognitive and psychosocial mechanisms that may also significantly contribute to the pain experience and could impact treatment outcomes. Indeed, clinical experience supports that a combination of self-management, non-pharmacological, and pharmacological approaches is needed to optimally manage pain in this population [1].

My research program is primarily focused on neurotrauma (SCI and TBI) and the neuropathic pains that so many experience after their injuries. My research integrates several areas of pain research with the long-term goal of better understanding the many factors that contribute to neuropathic pain development and severity as well as developing new treatment approaches to help people better manage their pain.

Spinal Cord Injury

Our research team has developed an educational resource named “SeePain” based on published pain literature and interviews with people living with SCI and chronic pain, their significant others, and healthcare providers with SCI expertise. The SeePain is a comprehensive guide for people with SCI and their significant others or family members that is intended to increase health literacy and facilitate communication between patients and their healthcare providers. The ultimate purpose of the SeePain is to help people with SCI to make pain manageable and reduce its negative impact on quality of life. This educational tool should be freely available shortly.

Additionally, my lab has received CDMRP funding to investigate the effects of a program designed to modulate cortical mechanisms via exercise and bodily illusions in combination with pain education. This ongoing study was developed in direct response to SCI stakeholders’ significant interest in non-pharmacological interventions and pain education [2], [3].

Furthermore, our research investigates cognitive mechanisms of multisensory body representation by means of electrophysiological methods including EEG and chronometric measures [4]–[6] to further understand the link between impaired multisensory body representation and neuropathic pain. This will help us to develop additional strategies to modulate neuropathic pain symptoms with non-pharmacological interventions.

Congruent with this, in a new CDMRP funded project that aims to investigate the brain’s ability to process body-related information using EEG, we will investigate how this may contribute to the development of neuropathic pain after SCI. In this project, we will also investigate the effects on neuropathic pain and sensory function after a series of non-invasive transcranial direct current stimulation in combination with bodily illusions.

Both these studies include qualitative interviews aiming to better understand how research participants perceive these types of interventions with the purpose of facilitating clinical translation.

Traumatic Brain Injury

More than 50% of individuals develop chronic pain following traumatic brain injury (TBI). Research suggests that a significant portion of post-TBI chronic pain conditions is neuropathic in nature, yet the relationship between neuropathic pain, psychological distress, and somatosensory function following TBI is not fully understood. In a recent study, we evaluated neuropathic pain symptoms, psychological and somatosensory function, and psychosocial factors in individuals with TBI [7]. This study suggested that neuropathic pain symptoms are relatively common after TBI and are not only associated with greater psychosocial distress but also with abnormal function of central pain processing pathways.

In a subsequent study, we investigated brain metabolite levels in people with TBI and chronic pain, TBI without chronic pain, and pain-free healthy controls [8]. The metabolite levels were obtained by whole-brain proton magnetic resonance spectroscopic imaging (¹H-MRSI) at 3 Tesla. The metabolite data included N-acetylaspartate, myo-inositol, total choline, glutamate plus glutamine, and total creatine. Associations between N-acetylaspartate levels and pain severity, neuropathic pain symptom severity, and psychological variables, including anxiety, depression, post-traumatic stress disorder (PTSD), and post-concussive symptoms, were also explored. The results of this study showed metabolite alterations in pain-related brain regions such as the frontal region, cingulum, postcentral gyrus, and thalamus in individuals with TBI with and without chronic pain. These results suggest that a combination of neuronal loss or dysfunction and maladaptive neuroplasticity may contribute to the development of persistent pain following TBI, although no causal relationship can be determined based on these data.

We have also investigated (a) the impact of pain across domains of attention, memory, and executive function, and (b) the relationships between pain and depression, anxiety, and post-traumatic stress disorder (PTSD) in persons with chronic TBI [9]. Those with TBI performed significantly worse on measures of semantic fluency when compared to controls and those with TBI who experienced pain scored significantly worse across all psychological assessments. We also found significant associations between measures of pain and most psychological symptoms. A follow-up stepwise linear regression among those in the TBI pain group indicated that post concussive complaints, pain severity, and neuropathic pain symptoms differentially contributed to symptoms of depression, anxiety, and PTSD. These findings suggest deficits in verbal fluency among those living with chronic TBI, with results also reinforcing the multidimensional nature of pain and its psychological significance in this population.

References

[1]          E. Loh et al., “The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update,” Spinal Cord, vol. 60, no. 6, Art. no. 6, Jun. 2022, doi: 10.1038/s41393-021-00744-z.

[2]          E. Widerstrom-Noga, K. D. Anderson, S. Perez, A. Martinez-Arizala, L. Calle-Coule, and L. Fleming, “Barriers and Facilitators to Optimal Neuropathic Pain Management: SCI Consumer, Significant Other, and Health Care Provider Perspectives,” Pain Medicine, vol. 21, no. 11, pp. 2913–2924, Nov. 2020, doi: 10.1093/pm/pnaa058.

[3]          E. Widerström-Noga, K. D. Anderson, S. Perez, A. Martinez-Arizala, and J. M. Cambridge, “Subgroup Perspectives on Chronic Pain and Its Management After Spinal Cord Injury,” The Journal of Pain, vol. 19, no. 12, pp. 1480–1490, Dec. 2018, doi: 10.1016/j.jpain.2018.07.003.

[4]          R. Vastano, M. Costantini, W. H. Alexander, and E. Widerstrom-Noga, “Multisensory integration in humans with spinal cord injury,” Sci Rep, vol. 12, no. 1, Art. no. 1, Dec. 2022, doi: 10.1038/s41598-022-26678-x.

[5]          R. Vastano, M. Costantini, and E. Widerstrom-Noga, “Maladaptive reorganization following SCI: The role of body representation and multisensory integration,” Progress in Neurobiology, vol. 208, p. 102179, Jan. 2022, doi: 10.1016/j.pneurobio.2021.102179.

[6]          R. Vastano and E. Widerstrom-Noga, “Event-related potentials during mental rotation of body-related stimuli in spinal cord injury population,” Neuropsychologia, p. 108447, Dec. 2022, doi: 10.1016/j.neuropsychologia.2022.108447.

[7]          L. E. Robayo et al., “Multidimensional pain phenotypes after Traumatic Brain Injury,” Frontiers in Pain Research, vol. 3, 2022, Accessed: Mar. 01, 2023. [Online]. Available: https://www.frontiersin.org/articles/10.3389/fpain.2022.947562.

[8]          L. E. Robayo et al., “Neurometabolite alterations in traumatic brain injury and associations with chronic pain,” Frontiers in Neuroscience, vol. 17, 2023, Accessed: Mar. 01, 2023. [Online]. Available: https://www.frontiersin.org/articles/10.3389/fnins.2023.1125128.

[9]          N. P. Cherup, L. E. Robayo, R. Vastano, L. Fleming, B. E. Levin, and E. Widerström-Noga, “Neuropsychological Function in Traumatic Brain Injury and the Influence of Chronic Pain,” Percept Mot Skills, p. 315125231174082, May 2023, doi: 10.1177/00315125231174082.