Neuropathic pain following traumatic spinal cord injury: Models, measurement, and mechanisms

Abstract

Neuropathic pain following spinal cord injury (SCI) is notoriously difficult to treat and is a high priority for many in the SCI population. Resolving this issue requires animal models fidelic to the clinical situation in terms of injury mechanism and pain phenotype. This Review discusses the means by which neuropathic pain has been induced and measured in experimental SCI and compares these with human outcomes, showing that there is a substantial disconnection between experimental investigations and clinical findings in a number of features. Clinical injury level is predominantly cervical, whereas injury in the laboratory is modeled mainly at the thoracic cord. Neuropathic pain is primarily spontaneous or tonic in people with SCI (with a relatively smaller incidence of allodynia), but measures of evoked responses (to thermal and mechanical stimuli) are almost exclusively used in animals. There is even the question of whether pain per se has been under investigation in most experimental SCI studies rather than simply enhanced reflex activity with no affective component. This Review also summarizes some of the problems related to clinical assessment of neuropathic pain and how advanced imaging techniques may circumvent a lack of patient/clinician objectivity and discusses possible etiologies of neuropathic pain following SCI based on evidence from both clinical studies and animal models, with examples of cellular and molecular changes drawn from the entire neuraxis from primary afferent terminals to cortical sensory and affective centers. © 2016 Wiley Periodicals, Inc.

Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI

“…This pain could develop through diverse clinical features with a low capability to be cured. In animal studies, the SCI-induced nociceptive hypersensitivity was correlated with severity of injury 18, 28 . In our modelling of unilateral SCI, animals displayed severe motor deficit that exceeded on average the level 1 on the Ashworth rating scale and lowered the level 7 on the BBB scale.…”

Cell biology of spinal cord injury and repair

“…[22][23][24]. In some cases, spontaneous synapse turnover and circuit reorganization can lead to maladaptive consequences such as muscle spasticity (25), autonomic dysreflexia (26), or neuropathic pain (27,28). In other cases, spontaneous circuit reorganization can be adaptive and restore function after incomplete SCI, as in the spontaneous bilateral locomotor recovery that occurs after unilateral hemisection SCI (Brown-Séquard syndrome) in spite of permanent loss of descending supraspinal connections on the injured side (23,24,(29)(30)(31)(32).…”

“…Such approaches have also shown benefit in regulating breathing (148) or autonomic functions such as bladder control (149). On the other hand, spontaneous synapse reorganization in spared but reactive neural tissue can lead to maladaptive consequences such as muscle spasticity (25), autonomic dysreflexia (26), or neuropathic pain (27,28). More work is needed to understand mechanisms that drive maladaptive or adaptive synapse formation after SCI and how they can be beneficially modulated.…”

Pain: From genes and proteins to cells in the living organism

“…More important, neuroimaging may serve as a diagnostic tool for painful conditions (Sergeeva et al, 2015). In this issue, Kramer et al (2017) review current experimental and clinical findings in the mechanisms of neuropathic pain, specifically the cellular and molecular pathways from primary afferent terminals to cortical sensory and affective centers. The authors highlight some of the problems related to the clinical assessment of neuropathic pain and propose that advanced imaging techniques may overcome patients' subjectivity.…”