Windup of Flexion Reflexes in Chronic Human Spinal Cord Injury: A Marker for Neuronal Plateau Potentials?

Abstract

The physiological basis of flexion spasms in individuals after spinal cord injury (SCI) may involve alterations in the properties of spinal neurons in the flexion reflex pathways. We hypothesize that these changes would be manifested as progressive increases in reflex response with repetitive stimulus application (i.e., "windup") of the flexion reflexes. We investigated the windup of flexion reflex responses in 12 individuals with complete chronic SCI. Flexion reflexes were triggered using trains of electrical stimulation of plantar skin at variable intensities and inter-stimulus intervals. For threshold and suprathreshold stimulation, windup of both peak ankle and hip flexion torques and of integrated tibialis anterior electromyographic activity was observed consistently in all patients at inter-stimulus intervals < or =3 s. For subthreshold stimuli, facilitation of reflexes occurred only at intervals < or =1 s. Similarly, the latency of flexion reflexes decreased significantly at intervals < or =1 s. Patients that were receiving anti-spasticity medications (e.g., baclofen) had surprisingly larger windup of reflex responses than those who did not take such medications, although this difference may be related to differences of spasm frequency between the groups of subjects. The results indicate that the increase in spinal neuronal excitability following a train of electrical stimuli lasts for < or =3 s, similar to previous studies of nociceptive processing. Such long-lasting increases in flexion reflex responses suggest that cellular mechanisms such as plateau potentials in spinal motoneurons, interneurons, or both, may partially mediate spinal cord hyperexcitability in the absence of descending modulatory input.

Beginning at the end: Repetitive firing properties in the final common pathway

“…They attributed this, at least in part, to a developed hypersensitivity of motoneurons to serotonin. Data have also been presented demonstrating that PICs likely play a role in motoneuron firing in humans following spinal cord injury (Gorassini et al, 2004; see also Hornby et al, 2003;Nickolls et al, 2004) and possibly in other conditions, such as cramps (Baldissera et al, 1991). These studies suggest that while the development of spasticity following spinal cord injury is multifactorial (involving, e.g., a variety of interneuronal pathways), the plasticity of motoneuron properties in this pathophysiological process must also be considered.…”

Spasticity after spinal cord injury

“…3 A recent study has provided evidence to implicate plateau potentials in the spinal interneuronal and motoneuronal circuitry in the hyperexcitability of flexion withdrawal reflexes in individuals with chronic SCI. 41 Intrasegmental polysynaptic connections cause the flexor reflex initiated by a localized stimulus to generate a widespread flexor spasm, which can appear as a coordinated flexion of all joints of the leg. 35,39 Management of spasticity following SCI In contrast to the general lack of agreement within the literature about the definition and evaluation of spasticity, there appears to be widespread agreement that decisions regarding the management of spasticity must be based on the goal of achieving balance between the useful and detrimental effects of spasticity on an individual's QOL.…”

Abnormal cutaneous flexor reflex activity during controlled isometric plantarflexion in human spinal cord injury spasticity syndrome

“…2 Furthermore, although exaggerated stretch and H reflex activity have been detected in the clinic and in an animal model of the spasticity syndrome, 6,51 these signs are not thought to contribute significantly to movement disorder after SCI. 52 Lower limb flexor CR excitability has often been reported to increase after SCI measured during passive 4,10,15,29,53 or active movement. 3,11,26,54 Furthermore, CR is actively modulated during passive movement, 55 balance 56 and gait.…”

“…2 Cutaneous reflex (CR) dysfunction has also been regarded as an additional sign of the spasticity syndrome following spinal cord injury (SCI), [3][4][5][6][7][8][9] especially when detected in subjects with hypertonia and increased tonic stretch reflexes. [10][11][12] In addition, abnormal flexor reflex excitability is present during subacute 4,13 and chronic SCI, 14,15 impacts on residual gait function after SCI 16 and interferes with daily activities. 17 Lower limb CR activity in humans is modulated by several segmental and descending control mechanisms, [18][19][20][21] and the loss of descending modulatory mechanisms may contribute to the SCI spasticity syndrome.…”