Methods for treating pain and painful syndromes in spinal cord injury: Medications, therapies, interventions, and neuromodulation

Introduction

Pain frequently limits activities, decreases quality of life, and leads to significant psychological impairment independent of other functional deficits after SCI ( ; ; ). In general, SCI pain is not well understood from the cellular, molecular, and even spinal cord pathway levels ( ).

Sixty-five percent to eighty percent of individuals with SCI live with chronic pain, and nearly one third rate this pain as severe ( ; ; ). About half of all individuals with SCI suffer from pain so severe that it interferes with function and rehabilitation independent of deficits related to their SCI ( ). It is generally believed that level of injury does not have an influence on the degree of post-SCI chronic pain. Penetrating injuries may be more likely to result in chronic pain ( ), and there is some evidence that incomplete lesions lead to more chronic pain than complete lesions ( ; ).

Pain after SCI can generally be divided into nociceptive, visceral, at-level neuropathic, and below-level neuropathic ( ). It is theorized that SCI pain may be fairly unique and related to relative serotonin, norepinephrine, and dopamine deficits due to loss of supraspinal inhibition ( ; ; ). Additionally, there is a well-described inflammatory milieu that occurs after SCI and may contribute to an additional inflammatory basis of pain ( ). Furthermore, post-SCI changes are noted in synaptic dendrites in individuals who experience significant pain, suggesting a dynamic neuroplastic component to pain ( ). It is likely the unique combination central nervous system (CNS) changes after SCI creates a “pro-pain” state, and not surprisingly, SCI pain is often refractory to medical treatments ( ; ).

The treatment of SCI-related pain often comes down to using a multimodal approach with medications, physical interventions, treatment of underlying conditions like spasticity, treatment of acquired overuse syndromes, and potentially the use of neuromodulation interventions. The typical categories of SCI-related pain can be reviewed in Tables 1 and 2 .

Application to other areas of neuroscience

There is a growing emphasis on the connection between physical experiences and psychologic interpretation that goes beyond pain management. One particular area of interest has been the neural pathway between the amygdala, periaqueductal gray matter, and rostral ventromedial medulla (RVM). The amygdala stores emotional experiences. It is connected to the periaqueductal gray matter, which contains a high concentration of opioid, cannabinoid, and endorphin receptors ( ). The RVM is not involved in generating an initial pain response but does help regulate the maintenance of neuropathic pain ( ). The ventral posteromedial nucleus plays a major role in central sensitization, a condition of the nervous system that is associated with development and maintenance of chronic pain that is caused by increased excitability of cell membranes, synaptic efficiency, and reduced inhibition of nociceptive pathways ( ). The plasticity of neurons that undergo central sensitization has been the target of newer therapies, though significant mechanistic gaps in our understanding remain ( ).

These pathways significantly influence pain processing, decision-making, avoidant behavior, and personality expression ( ) and are thought to modulate opioid-induced analgesia ( ). Additionally, recent studies showed modulating this pathway impacts the extent of depression-associated pain in mice under chronic stress ( ). Physical activity, such as Tai Chi and cycling, has been shown to modulate this opioid pathway, thereby reducing overall pain levels and reducing levels of circulating inflammatory markers ( ). This concept is fundamental to the use of physical activity to combat pain in patients with depression.

Main narrative text