Longitudinal study of wind-up responses after graded spinal cord injuries in the adult rat.

PURPOSE The main objectives of this work were to evaluate the development of neuropathic pain after spinal cord injuries of different severities, and to assess changes in central excitability and plasticity by means of wind-up responses and withdrawal reflexes. METHODS Two groups of rats were subjected to spinal cord contusion with forces of 100 or 200 kdyn applied at T8. Measurements of thermal and mechanical pain thresholds as well as wind-up measurements were performed weekly during two months after injury. Withdrawal reflexes were also assessed electrophysiologically. RESULTS We found that animals with contusion of different severities showed a similar reduction in nociceptive thresholds. All contused animals showed increased wind-up responses compared to intact animals during the first 2 to 6 weeks post injury. The mean increase of wind-up was higher in rats with stronger spinal cord contusion. Results from the withdrawal reflexes did not correlate with nociceptive behaviors nor wind-up responses, highlighting the plasticity of spinal circuits modulation after SCI. CONCLUSION These results indicate that the graded-force spinal cord contusion model is suitable for studying central neuropathic pain, and for assessing changes in wind-up responses. Wind-up measurements can be used as a non-invasive technique to detect changes in central excitability after SCI of different severities.

[1]  D. R. Marsh,et al.  Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury. , 2010, Journal of neurotrauma.

[2]  Bruschi,et al.  Classification of , 2010 .

[3]  X. Navarro,et al.  Functional involvement of the lumbar spinal cord after contusion to T8 spinal segment of the rat. , 2010, Restorative neurology and neuroscience.

[4]  Y. Koninck,et al.  Chemokines and pain mechanisms , 2009, Brain Research Reviews.

[5]  D. Burke,et al.  Spinal cord contusion based on precise vertebral stabilization and tissue displacement measured by combined assessment to discriminate small functional differences. , 2008, Journal of neurotrauma.

[6]  G. Wasner,et al.  Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. , 2008, Brain : a journal of neurology.

[7]  D. Basso,et al.  Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats , 2008, Experimental Neurology.

[8]  R. Quirion,et al.  Does COX2-dependent PGE2 play a role in neuropathic pain? , 2008, Neuroscience Letters.

[9]  H. Mehdorn,et al.  Force-dependent development of neuropathic central pain and time-related CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat. , 2008, Journal of neurotrauma.

[10]  S. Kimura,et al.  Separate recording of A-delta and C fiber-mediated nociceptive flexor reflex responses of mouse hindlimb using electromyography and the characteristics of wind-up appearing in the responses. , 2008, Journal of pharmacological sciences.

[11]  Hosung Jung,et al.  Chemokines and the pathophysiology of neuropathic pain , 2007, Proceedings of the National Academy of Sciences.

[12]  J. Benito-Penalva,et al.  [Characteristics of chronic neuropathic pain and their relationship with psychological well-being in spinal cord injury patients]. , 2007, Revista de neurologia.

[13]  S. Waxman,et al.  Activated Microglia Contribute to the Maintenance of Chronic Pain after Spinal Cord Injury , 2006, The Journal of Neuroscience.

[14]  R. Yezierski.  Spinal Cord Injury: A Model of Central Neuropathic Pain , 2005, Neurosignals.

[15]  Stephen B. McMahon,et al.  Immune and glial cell factors as pain mediators and modulators , 2005, Experimental Neurology.

[16]  S. Whittemore,et al.  Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat , 2005, Experimental Neurology.

[17]  M. Gorassini,et al.  Persistent inward currents in motoneuron dendrites: Implications for motor output , 2005, Muscle & nerve.

[18]  John Harris,et al.  The organization of motor responses to noxious stimuli , 2004, Brain Research Reviews.

[19]  X. Navarro,et al.  Reorganization of reflex responses mediated by different afferent sensory fibers after spinal cord transection. , 2004, Journal of neurophysiology.

[20]  L. Arendt-Nielsen,et al.  Electrophysiological characterization of facilitated spinal withdrawal reflex to repetitive electrical stimuli and its modulation by central glutamate receptor in spinal anesthetized rats , 2004, Brain Research.

[21]  M. Jacquin,et al.  Mechanical and cold allodynia in a rat spinal cord contusion model , 2004, Somatosensory & motor research.

[22]  W. Willis,et al.  Temporal plasticity of dorsal horn somatosensory neurons after acute and chronic spinal cord hemisection in rat , 2003, Brain Research.

[23]  Alexander Sasha Rabchevsky,et al.  Experimental modeling of spinal cord injury: characterization of a force-defined injury device. , 2003, Journal of neurotrauma.

[24]  R. Yezierski,et al.  Chronic pain after spinal injury: interference with sleep and daily activities. , 2001, Archives of physical medicine and rehabilitation.

[25]  F. Lenz,et al.  Plasticity of pain-related neuronal activity in the human thalamus. , 2006, Progress in brain research.

[26]  C. Woolf,et al.  Pain: molecular mechanisms. , 2000, The journal of pain : official journal of the American Pain Society.

[27]  D. Basso,et al.  Neuroanatomical substrates of functional recovery after experimental spinal cord injury: implications of basic science research for human spinal cord injury. , 2000, Physical therapy.

[28]  J. Lopez-Garcia,et al.  Wind-up of spinal cord neurones and pain sensation: much ado about something? , 2000, Progress in Neurobiology.

[29]  P. Eide,et al.  Wind‐up and the NMDA receptor complex from a clinical perspective , 2000, European journal of pain.

[30]  K. Hole,et al.  Some problems with wind-up and its calculation. , 1999, Pain.

[31]  J. Willer,et al.  Temporal summation of C-fiber afferent inputs: competition between facilitatory and inhibitory effects on C-fiber reflex in the rat. , 1997, Journal of neurophysiology.

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

[33]  Deborah A Taylor,et al.  Classification of pain following spinal cord injury , 1997, Spinal Cord.

[34]  C. Hulsebosch,et al.  Mechanical and thermal allodynia in chronic central pain following spinal cord injury , 1996, Pain.

[35]  C. Woolf.  Windup and central sensitization are not equivalent. , 1996, Pain.

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

[37]  Xiao-jun Xu,et al.  Plasticity in spinal nociception after peripheral nerve section: reduced effectiveness of the NMDA receptor antagonist MK-801 in blocking wind-up and central sensitization of the flexor reflex , 1995, Brain Research.

[38]  R. Young.  Spasticity: A review , 1994, Neurology.

[39]  C. Woolf,et al.  Rate of rise of the cumulative depolarization evoked by repetitive stimulation of small-caliber afferents is a predictor of action potential windup in rat spinal neurons in vitro. , 1993, Journal of neurophysiology.

[40]  J W Little,et al.  Lower Extremity Manifestations of Spasticity in Chronic Spinal Cord Injury , 1989, American journal of physical medicine & rehabilitation.

[41]  R. Dubner,et al.  A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia , 1987, Pain.

[42]  D. Lodge,et al.  Evidence for involvement ofN-methylaspartate receptors in ‘wind-up’ of class 2 neurones in the dorsal horn of the rat , 1987, Brain Research.

[43]  A. Dickenson,et al.  Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurones following c fibre stimulation. , 1987, Neuropharmacology.

[44]  C. Woolf.  Evidence for a central component of post-injury pain hypersensitivity , 1983, Nature.

[45]  James W. Lance,et al.  The control of muscle tone, reflexes, and movement , 1980, Neurology.

[46]  L M Mendell,et al.  Physiological properties of unmyelinated fiber projection to the spinal cord. , 1966, Experimental neurology.