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Nociceptive input diminishes recovery and increases lesion area after a spinal cord injury (SCI). Recent work has linked these effects to the expansion of hemorrhage at the site of injury. The current article examines whether these adverse effects are linked to a pain-induced rise in blood pressure (BP) and/or flow. Male rats with a low-thoracic SCI were treated with noxious input (electrical stimulation [shock] or capsaicin) soon after injury. Locomotor recovery and BP were assessed throughout. Tissues were collected 3 h, 24 h, or 21 days later. Both electrical stimulation and capsaicin undermined locomotor function and increased the area of hemorrhage. Changes in BP/flow varied depending on type of noxious input, with only shock producing changes in BP. Providing behavioral control over the termination of noxious stimulation attenuated the rise in BP and hemorrhage. Pretreatment with the α-1 adrenergic receptor inverse agonist, prazosin, reduced the stimulation-induced rise in BP and hemorrhage. Prazosin also attenuated the adverse effect that noxious stimulation has on long-term recovery. Administration of the adrenergic agonist, norepinephrine 1 day after injury induced an increase in BP and disrupted locomotor function, but had little effect on hemorrhage. Further, inducing a rise in BP/flow using norepinephrine undermined long-term recovery and increased tissue loss. Mediational analyses suggest that the pain-induced rise in blood flow may foster hemorrhage after SCI. Increased BP appears to act through an independent process to adversely affect locomotor performance, tissue sparing, and long-term recovery.

Spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma), which engages pain (nociceptive) fibers. Prior research has shown that nociceptive input can increase cell death, expand the area of hemorrhage, and impair long-term recovery. The current study shows that these adverse effects can be blocked by the sodium channel blocker lidocaine applied rostral to a contusion injury. Rats received a lower thoracic (T12) contusion injury, and noxious electrical stimulation (shock) was applied to the tail 24 h later. Immediately before shock treatment, a pharmacological transection was performed by slowly infusing lidocaine at T2. Long-term locomotor recovery was assessed over the next 21 days. Noxious electrical stimulation impaired locomotor recovery, and this effect was blocked by rostral lidocaine. Next, the acute effect of lidocaine was assessed. Tissue was collected 3 h after noxious stimulation, and the extent of hemorrhage was evaluated by assessing hemoglobin content using Western blotting. Nociceptive stimulation increased the extent of hemorrhage. Lidocaine applied at T2 before, but not immediately after, stimulation blocked this effect. A similar pattern of results was observed when lidocaine was applied at the site of injury by means of a lumbar puncture. The results show that a pharmacological transection blocks nociception-induced hemorrhage and exacerbation of locomotor deficits.

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain. [ABSTRACT FROM AUTHOR]

Pain (nociceptive) input soon after spinal cord injury (SCI) expands the area of tissue loss (secondary injury) and impairs long-term recovery. Evidence suggests that nociceptive stimulation has this effect because it promotes acute hemorrhage. Disrupting communication with the brain blocks this effect. The current study examined whether rostral systems exacerbate tissue loss because pain input drives an increase in systolic blood pressure (BP) and flow that fuels blood infiltration. Rats received a moderate contusion injury to the lower thoracic (T12) spinal cord. Communication with rostral processes was disrupted by cutting the spinal cord 18 h later at T2. Noxious electrical stimulation (shock) applied to the tail (Experiment 1), or application of the irritant capsaicin to one hind paw (Experiment 2), increased hemorrhage at the site of injury. Shock, but not capsaicin, increased systolic BP and tail blood flow in sham-operated rats. Cutting communication with the brain blocked the shock-induced increase in systolic BP and tail blood flow. Experiment 3 examined the effect of artificially driving a rise in BP with norepinephrine (NE) in animals that received shock. Spinal transection attenuated hemorrhage in vehicle-treated rats. Treatment with NE drove a robust increase in BP and tail blood flow but did not increase the extent of hemorrhage. The results suggest pain input after SCI can engage rostral processes that fuel hemorrhage and drive sustained cardiovascular output. An increase in BP was not, however, necessary or sufficient to drive hemorrhage, implicating other brain-dependent processes. [ABSTRACT FROM AUTHOR]

The present review explores the concept of learning within the context of neurorehabilitation after spinal cord injury (SCI). The aim of physical therapy and neurorehabilitation is to bring about a lasting change in function—to encourage learning. Traditionally, it was assumed that the adult spinal cord is hardwired—immutable and incapable of learning. Research has shown that neurons within the lower (lumbosacral) spinal cord can support learning after communication with the brain has been disrupted by means of a thoracic transection. Noxious stimulation can sensitize nociceptive circuits within the spinal cord, engaging signal pathways analogous to those implicated in brain-dependent learning and memory. After a spinal contusion injury, pain input can fuel hemorrhage, increase the area of tissue loss (secondary injury), and undermine long-term recovery. Neurons within the spinal cord are sensitive to environmental relations. This learning has a metaplastic effect that counters neural over-excitation and promotes adaptive learning through an up-regulation of brain-derived neurotrophic factor (BDNF). Exposure to rhythmic stimulation, treadmill training, and cycling also enhances the expression of BDNF and counters the development of nociceptive sensitization. SCI appears to enable plastic potential within the spinal cord by down-regulating the Cl− co-transporter KCC2, which reduces GABAergic inhibition. This enables learning, but also fuels over-excitation and nociceptive sensitization. Pairing epidural stimulation with activation of motor pathways also promotes recovery after SCI. Stimulating motoneurons in response to activity within the motor cortex, or a targeted muscle, has a similar effect. It is suggested that a neurofunctionalist approach can foster the discovery of processes that impact spinal function and how they may be harnessed to foster recovery after SCI. • Spinal cord injury (SCI) enables plasticity by reducing GABA-dependent inhibition • Pain input after SCI induces sensitization, fosters hemorrhage and impairs recovery • Controllable/predictable stimulation increases BDNF and promotes adaptive plasticity • Neurorehabilitative strategies that involve relational learning have a lasting effect • Procedures that introduce periodic (regular) stimulation promote adaptive plasticity [ABSTRACT FROM AUTHOR]