An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

Study Design:Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model.Methods:Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons.Results:The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model.Conclusion:The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system.

[1]  C. Hulsebosch,et al.  Chronic central pain after spinal cord injury. , 1997, Journal of neurotrauma.

[2]  Adam R Ferguson,et al.  Instrumental learning within the spinal cord: underlying mechanisms and implications for recovery after injury. , 2006, Behavioral and cognitive neuroscience reviews.

[3]  J Schouenborg,et al.  Functional organization of the nociceptive withdrawal reflexes , 1992, Experimental Brain Research.

[4]  M. Popovic,et al.  Gait training regimen for incomplete spinal cord injury using functional electrical stimulation , 2006, Spinal Cord.

[5]  E. Field-Fote,et al.  Improved intralimb coordination in people with incomplete spinal cord injury following training with body weight support and electrical stimulation. , 2002, Physical therapy.

[6]  J. Broton,et al.  Interlimb reflex activity after spinal cord injury in man: strengthening response patterns are consistent with ongoing synaptic plasticity , 2005, Clinical Neurophysiology.

[7]  W D Willis,et al.  Role of Neurotransmitters in Sensitization of Pain Responses , 2001, Annals of the New York Academy of Sciences.

[8]  E. Field-Fote Combined use of body weight support, functional electric stimulation, and treadmill training to improve walking ability in individuals with chronic incomplete spinal cord injury. , 2001, Archives of physical medicine and rehabilitation.

[9]  V. Edgerton,et al.  Plasticity of the spinal neural circuitry after injury. , 2004, Annual review of neuroscience.

[10]  G E Loeb,et al.  Neural signals for command control and feedback in functional neuromuscular stimulation: a review. , 1996, Journal of rehabilitation research and development.

[11]  J. Sandkühler,et al.  Induction of long‐term potentiation at spinal synapses by noxious stimulation or nerve injury , 1998, The European journal of neuroscience.

[12]  S. Tonegawa,et al.  Hippocampal CA3 NMDA Receptors Are Crucial for Adaptive Timing of Trace Eyeblink Conditioned Response , 2006, The Journal of Neuroscience.

[13]  Mehdi M Mirbagheri,et al.  The effect of locomotor training combined with functional electrical stimulation in chronic spinal cord injured subjects: walking and reflex studies , 2002, Brain Research Reviews.

[14]  Adam R Ferguson,et al.  Instrumental learning within the spinal cord: V. Evidence the behavioral deficit observed after noncontingent nociceptive stimulation reflects an intraspinal modification , 2003, Behavioural Brain Research.

[15]  K. Sluka,et al.  Transcutaneous electrical nerve stimulation (TENS) reduces chronic hyperalgesia induced by muscle inflammation , 2006, Pain.

[16]  Adam R Ferguson,et al.  Instrumental learning within the spinal cord: IV. Induction and retention of the behavioral deficit observed after noncontingent shock. , 2002, Behavioral neuroscience.

[17]  P. Peckham,et al.  Functional electrical stimulation for neuromuscular applications. , 2005, Annual review of biomedical engineering.

[18]  Adam R Ferguson,et al.  Nociceptive plasticity inhibits adaptive learning in the spinal cord , 2006, Neuroscience.

[19]  M. Ladouceur,et al.  Functional electrical stimulation-assisted walking for persons with incomplete spinal injuries: changes in the kinematics and physiological cost of overground walking. , 2000, Scandinavian journal of rehabilitation medicine.

[20]  J. Grau,et al.  Instrumental learning in spinalized rats : the induction of central sensitization undermines behavioral plasticity in the spinal cord , 2008 .

[21]  J. Grau,et al.  Latent inhibition, overshadowing, and blocking of a conditioned antinociceptive response in spinalized rats. , 1994, Behavioral and neural biology.

[22]  Adam R Ferguson,et al.  GABA(A) receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats. , 2003, Behavioral neuroscience.

[23]  M. Seligman,et al.  Learned helplessness: Theory and evidence. , 1976 .

[24]  R. Joynes,et al.  Neonatal hind-paw injury disrupts acquisition of an instrumental response in adult spinal rats. , 2007, Behavioral neuroscience.

[25]  R. Dubner,et al.  Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  M. Fanselow,et al.  Differential effects of the N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues. , 1994, Behavioral neuroscience.

[27]  R. Malenka Synaptic Plasticity and AMPA Receptor Trafficking , 2003, Annals of the New York Academy of Sciences.

[28]  Adam R Ferguson,et al.  A simple post hoc transformation that improves the metric properties of the BBB scale for rats with moderate to severe spinal cord injury. , 2004, Journal of neurotrauma.

[29]  J. Grau,et al.  Instrumental learning within the spinal cord: VI The NMDA receptor antagonist, AP5, disrupts the acquisition and maintenance of an acquired flexion response , 2004, Behavioural Brain Research.

[30]  J. Grau,et al.  Activation of the opioid and nonopioid hypoalgesic systems at the level of the brainstem and spinal cord: does a coulometric relation predict the emergence or form of environmentally induced hypoalgesia? , 1993, Behavioral neuroscience.

[31]  Adam R Ferguson,et al.  Instrumental Learning within the Rat Spinal Cord: Localization of the Essential Neural Circuit , 2005 .

[32]  J. Mao,et al.  Spinal Cord Neuroplasticity following Repeated Opioid Exposure and Its Relation to Pathological Pain , 2001, Annals of the New York Academy of Sciences.

[33]  D. Basso,et al.  A sensitive and reliable locomotor rating scale for open field testing in rats. , 1995, Journal of neurotrauma.

[34]  L. Mendell,et al.  BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs , 2003, The European journal of neuroscience.

[35]  P. Wall,et al.  Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  Adam R Ferguson,et al.  Uncontrollable stimulation undermines recovery after spinal cord injury. , 2004, Journal of neurotrauma.

[37]  P. J. Hope,et al.  Evidence for localized release of substance P within rat spinal cord evoked by physiological and electrical stimuli , 1994, Neuropeptides.

[38]  J G Chen,et al.  Low-Frequency Stimulation of Afferent Aδ-Fibers Induces Long-Term Depression at Primary Afferent Synapses with Substantia Gelatinosa Neurons in the Rat , 1997, The Journal of Neuroscience.

[39]  Adam R Ferguson,et al.  Instrumental learning within the spinal cord II. Evidence for central mediation , 2002, Physiology & Behavior.

[40]  S. Rossignol,et al.  Recovery of locomotion in the cat following spinal cord lesions , 2002, Brain Research Reviews.

[41]  J. Schouenborg,et al.  Functional organization of the nociceptive withdrawal reflexes , 2004, Experimental Brain Research.

[42]  J. Grau,et al.  Instrumental learning within the spinal cord: III. Prior exposure to noncontingent shock induces a behavioral deficit that is blocked by an opioid antagonist , 2004, Neurobiology of Learning and Memory.

[43]  H Barbeau,et al.  Walking after spinal cord injury: evaluation, treatment, and functional recovery. , 1999, Archives of physical medicine and rehabilitation.

[44]  J W Grau,et al.  Instrumental learning within the spinal cord: I. Behavioral properties. , 1998, Behavioral neuroscience.

[45]  W. Willis Long-term potentiation in spinothalamic neurons , 2002, Brain Research Reviews.

[46]  M. Bear,et al.  Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity , 2000, Nature.

[47]  J. Grau,et al.  Preserving and restoring behavioral potential within the spinal cord using an instrumental training paradigm. , 2001, Journal of neurophysiology.

[48]  R. Triolo,et al.  Clinical Applications of Electrical Stimulation After Spinal Cord Injury , 2004, The journal of spinal cord medicine.

[49]  J. A. Gruner,et al.  A monitored contusion model of spinal cord injury in the rat. , 1992, Journal of neurotrauma.

[50]  K. Pearson,et al.  Fictive motor patterns in chronic spinal cats. , 1991, Journal of neurophysiology.