When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury. Academic Article uri icon


  • Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects. SCI sets the stage for nociceptive sensitization by disrupting serotonergic (5HT) fibers that quell overexcitation. The loss of 5HT can enhance neural excitability by reducing membrane-bound K+-Cl- cotransporter 2, a cotransporter that regulates the outward flow of Cl-. This increases the intracellular concentration of Cl-, which reduces the hyperpolarizing (inhibitory) effect of gamma-aminobutyric acid. Uncontrollable noxious stimulation also undermines the recovery of locomotor function, and increases behavioral signs of chronic pain, after a contusion injury. Nociceptive stimulation has a greater effect if experienced soon after SCI. This adverse effect has been linked to a downregulation in brain-derived neurotrophic factor and an upregulation in the cytokine, tumor necrosis factor. Noxious input enhances tissue loss at the site of injury by increasing the extent of hemorrhage and apoptotic/pyroptotic cell death. Intrathecal lidocaine blocks nociception-induced hemorrhage, cellular indices of cell death, and its adverse effect on behavioral recovery. Clinical implications are discussed.

published proceedings

  • J Neurotrauma

altmetric score

  • 3.5

author list (cited authors)

  • Grau, J. W., Huang, Y., Turtle, J. D., Strain, M. M., Miranda, R. C., Garraway, S. M., & Hook, M. A.

citation count

  • 30

complete list of authors

  • Grau, James W||Huang, Yung-Jen||Turtle, Joel D||Strain, Misty M||Miranda, Rajesh C||Garraway, Sandra M||Hook, Michelle A

publication date

  • January 2017