Spinal neurons exhibit a surprising capacity to learn and a hidden vulnerability when freed from the brain’s control

Grau, James W.; Hook, Michelle A.

doi:10.1007/s11910-006-0001-3

Cited by 11 publications

(5 citation statements)

References 23 publications

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“…120 We have detailed how these processes work using a transection paradigm, demonstrating that learning can occur without input from the brain. 27,55,120,121 This work reinforces the idea that physical rehabilitation can benefit recovery after severe injury by engaging spinal circuits caudal to injury. 39,122 Our work also reminds us that noxious stimulation can impact neural function in the absence of pain reports and that its adverse effect can be minimized by presenting stimuli in a predictable/controllable manner.…”

Section: Implications For Recovery After a Contusion Injurysupporting

confidence: 69%

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury

Grau

Huang

Turtle

et al. 2017

Journal of Neurotrauma

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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.

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Section: Implications For Recovery After a Contusion Injurysupporting

confidence: 69%

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury

Grau

Huang

Turtle

et al. 2017

Journal of Neurotrauma

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“…Our previous studies have shown that uncontrollable electrical stimulation undermines the adaptive plasticity of the spinal cord, and renders the system incapable of instrumental conditioning (Grau et al, 1998, 2006; Grau & Hook, 2006). Ferguson et al (2006) suggested that this learning deficit is due to the development of a state akin to central sensitization.…”

Section: Discussionmentioning

confidence: 99%

Peripheral inflammation undermines the plasticity of the isolated spinal cord.

Hook

Huie

Grau

2008

Behavioral Neuroscience

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112

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Peripheral capsaicin treatment induces molecular changes that sensitize the responses of nociceptive neurons in the spinal dorsal horn. The current studies demonstrate that capsaicin also undermines the adaptive plasticity of the spinal cord, rendering the system incapable of learning a simple instrumental task. In these studies, male rats are transected at the second thoracic vertebra and are tested 24 to 48 hours later. During testing, subjects receive shock to one hindleg when it is extended (controllable stimulation). Rats quickly learn to maintain the leg in a flexed position. Rats that have been injected with capsaicin (1% or 3%) in the hindpaw fail to learn, even when tested on the leg contralateral to the injection. This learning deficit lasts at least 24 hours. Interestingly, training with controllable electrical stimulation prior to capsaicin administration protects the spinal cord against the maladaptive effects. Rats pretrained with controllable stimulation do not display a learning deficit or tactile allodynia. Moreover, controllable stimulation, combined with naltrexone, reverses the capsaicin-induced deficit. These data suggest that peripheral inflammation, accompanying spinal cord injuries, might have an adverse effect on recovery.

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“…This process is thought to underlie some chronic pain conditions (Ji, Kohno, Moore, & Woolf, 2003; Khasabov et al, 2002; Ma & Woolf, 1997; Mannion & Woolf, 2000; Woolf, 1996). In addition, manipulations used to induce central sensitization have profound effects on spinal instrumental performance (Ferguson et al, 2006; Grau & Hook, 2006). In the case of neonatal injury, it appears that altered pain processing impairs the ability of the spinal cord to support behavioral change in response to experience (reduced spinal behavioral plasticity).…”

Section: Discussionmentioning

confidence: 99%

Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

Young

Baumbauer

Hillyer

et al. 2007

Behavioral Neuroscience

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Recent findings indicate that neonatal injury results in decreased spinal plasticity in adult subjects (E. E. Young, K. M. Baumbauer, A. E. Elliot, & R. L. Joynes, 2007). Previous research has shown that acute manipulations of pain processing (i.e., administration of formalin, carrageenan, capsaicin) result in a loss of spinal behavioral plasticity (A. R. Ferguson, E. D. Crown, & J. W. Grau, 2006). Moreover, neonatal injury results in a lasting reduction in adult spinally mediated plasticity resembling the deficit seen following acute manipulations in adults (E. E. Young et al., 2007). The present study was designed to determine whether the effects of neonatal injury could be prevented by lidocaine administration during the initial healing period. Subjects (injured or uninjured) received lidocaine or saline on 1 of 4 administration schedules (preinjury only, postinjury only, for 24 hr postsurgery, or for 72 hr postsurgery). Results demonstrated that lidocaine administration did not prevent the hypersensitivity and reduced spinal plasticity associated with neonatal injury. This suggests that (a) the mechanisms underlying neonatal injury are independent of peripheral input in the initial healing period and (b) lidocaine is ineffective at preventing long-term spinal plasticity changes following neonatal injury.

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Spinal neurons exhibit a surprising capacity to learn and a hidden vulnerability when freed from the brain’s control

Cited by 11 publications

References 23 publications

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury

Peripheral inflammation undermines the plasticity of the isolated spinal cord.

Local anesthetic treatment significantly attenuates acute pain responding but does not prevent the neonatal injury-induced reduction in adult spinal behavioral plasticity.

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